A Computational Study of a Prebiotic Synthesis of Ergosterol,
Ergocalciferol & Cholecalciferol (Vitamin D2 and D3)
NIGEL AYLWARD
BMS Education Services Company,
Sea Meadow House, Road Town, Tortola,
BRITISH VIRGIN ISLANDS
Abstract: - The magnesium ion metalloporphyrin complex is shown to bind the ligands ethyne (e) and propyne
(p) on the metal or nitrogen pyrrole sites as a two-site catalyst in their copolymerization. The order of addition
of the monomers is (epep) to form the side-chain. The steroid ring D (pep) is formed first from the propyne
adduct bound to the metal site and the nonane adduct bound to the N-site. The optimal orientation of these
adducts determines the β-orientation of the 17-substituent. Further addition of three ethyne monomers forms an
N-diene cyclopentene derivative able to cyclise to form the steroid ring C (pee) with a trans conformation and a
13-β methyl substituent. Further addition of propyne forms the B-ring (eep), followed by two ethyne to form
the A-ring (pee). Reaction with a hydroxyl anion and a proton allows the catalyst to separate. Final
hydrogenation renders ergosterol, photolysis leading to ergocalciferol (Vitamin D2).
The reactions have been shown to be feasible from the overall enthalpy changes in the ZKE approximation at
the HF and MP2 /6-31G* level, and with acceptable activation energies.
Key-Words: - Prebiotic photochemical synthesis, ergosterol, ergocalciferol (vitamin D2), cholecalciferol
(vitamin D3), Mg.porphin
Received: April 26, 2022. Revised: February 14, 2023. Accepted: March 12, 2023. Published: April 4, 2023.
1 Introduction
Ergosterol, (22E)-ergosta-5,7,22-trien-3β-ol), [1],
[2], a yeast sterol, [3], Fig. 8, is converted by
irradiation into ergocalciferol (Vitamin D2), whilst
7-dehydrocholesterol, common in animal tissues is
converted by radiation into cholecalciferol (Vitamin
D3). 7-dehydrocholesterol in the skin is the natural
precursor of cholecalciferol in man, [3], whilst fish-
liver oils are another source, [3]. Vitamin-D and its
receptor (VDR), [4], participate in the regulatory
machinery of gene control for skeletal development
involving intestinal calcium and phosphate
absorption, [5]. Dietary deficiency of vitamin D is
regarded as the main causative factor for the
development of rickets, [6]. Ergosterol is the form
of vitamin D usually found in vitamin supplements,
[7]. It is considered the first vitamin D analogue.
The structural modifications from cholecalciferol
reduce the affinity of ergocalciferol for the vitamin
D binding protein resulting in faster clearance,
limiting its activation, and altering its catabolism,
[8].
Ergosterol regulates membrane fluidity and
structure and is an important target for the activity
of antifungals, [9].
These steroids are both derivatives of the
saturated tetracyclic hydrocarbon,
perhydrocyclopentane phenanthrene, [3]. This has
six centres of asymmetry, [2], arising from the
fusion of the four rings where the numbering and
designation are standard, [1]. This steroid is closely
related to the terpenes, [10], constructed of
multiples of the five-carbon hydrocarbon isoprene
(2-methyl-1,3-butadiene). The biosynthesis of
ergosterol and cholesterol is from the steroid
lanosterol, [11], [39], formed from the isoprene
units of squalene (a dihydrotriterpene) consisting of
consecutive isoprene units, [3].
From a prebiotic perspective, [12], it is desirable
if the reactant molecules formed spontaneously from
a supposed mildly reducing prebiotic atmosphere,
[3], [13], whose constituents included hydrocarbon
gases such as ethyne (e), propyne (p), carbon
monoxide, ammonia, water, and hydrogen. Such an
atmosphere has been shown to render possible and
probable the formation of vitamins such as Vitamin
B12, [14], thyroxine (T3 and T4), [15], hormones
such as progesterone, [16], [40], stereospecific
amino acids, [17], and lipoic acid. Critical to these
prebiotic syntheses was the catalyst Mg.porphin,
able to activate diverse reactions between weakly
bonded charge transfer adducts on its surface to
form classes of biological molecules such as D-
sugars, L-amino acids, and terpenes, [18], [19].
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This paper proposes a model for the catalytic
photochemically activated copolymerization of
these gases to form ergosterol where the order of
polymerization is (epepepeeepee) on the catalyst
magnesium porphin, and involves some
hydroxylation and hydrogenation. The ergosterol
may under photolysis give Vitamin D2.
The prebiotic synthesis of cholecalciferol is
very similar and both closely follow that of the
prebiotic synthesis of the steroid hormone
progesterone, [16], [40].
The reactions described have been deduced as
kinetically and thermodynamically viable, but
photochemical excitation is required.
2 Problem Formulation
This proposed computational study of a plausible
synthesis of the steroid ergosterol involves the
calculation of the enthalpy changes for reaction
intermediates in the ZKE approximation and the
calculation of activation energies at the HF level.
These activation energies may all be accessible as
the catalyst may absorb appreciable photochemical
activation (0.21 h). The computations tabulated in
this paper used the GAUSSIAN09, [20].
The standard calculations at the HF and MP2
levels including zero-point energy corrections are as
previously published, [12].
3 Problem Solution
3.1 Total Energies (hartrees)
The steroid is described as being formed as a
copolymerzation of the gases ethyne and propyne on
the two site catalyst Mg.porphin. References
prefaced by steroid refer to the standard steroid
numbering as shown, in Fig. 1, [1].
Fig. 1: Standard steroid substituent numbering, [1].
The gas ethyne may form two adducts with the
catalyst on the metal and N-pyrrole sites, as follows.
The enthalpy of formation of the van der Waals
complex is small but it appears stable.
Mg.porphin is a powerful catalyst able to form
charge transfer complexes with a number of
different kinds of molecules, [21], [22]. With
ethyne, the ligand is positively charged (0.08) and
the porphin has a negative charge, The acetylene
sets as a ligand with a linear H-C ≡ C-H structure as
shown.
Mg.1,porphin + H-C ≡ C- H →
(1)
Mg.1, ethynyl.porphin
ΔH = -0.01421 h
The Mg.ethynyl.porphin may be photochemically
excited for the ethyne to migrate to bond with a
pyrrole unit as a higher energy ethyne adduct, [18],
as shown,
Mg.1, ethynyl.porphin →
Mg.1, porphin.ethynyl (2)
ΔH = 0.01353 h
The charge on the adduct is 0.07.
The gas propyne may also form two adducts with
the catalyst on the metal and N-pyrrole sites, as
follows:
The enthalpy of formation of the van der Waals
complex is small but it appears stable.
Mg.porphin + CH3-C ≡ C- H →
CCH H
+
Mg.porphin.N-
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Mg.1,CH3-C ≡ C- C-H.porphin (3)
ΔH = -0.00209 h
The charge on the propyne adduct is 0.07.
Mg.1, CH3-C ≡ C-H.porphin →
(4)
Mg.1, porphin. CH3-C ≡ C-H
ΔH = 0.01862 h
The charge on the propyne adduct was 0.19.
The first of these complexes on the metal site is
lower in energy than the corresponding complex on
the N-pyrrole site.
These complexes are integral reactants in the
proposed synthesis. The energies of the stable
complexes are shown in Table 1.
Table 1. MP2 /6-31G* total energies and zero point
energies (hartrees) for the respective equilibrium
geometries
Molecule MP2 ZPE (HF)
hartree hartree
Mg.porphin -1185.12250 0.29262
ethyne 77.06679 0.02945
Mg.1, ethynyl.porphin
-1262.19985 0.31797
Mg.1, porphin.ethynyl
-1262.18547 0.31701
propyne 116.24181 0.06010
Mg.1,propynyl.porphin
-1301.36738 0.35382
Mg.1,porphin.propynyl
-1301.34810 0.35308
ergosterol -1164.48771 0.70897
Mg.1,propynyl.porphin.ethynyl
-1378.46158 0.37965
Mg.1,4-dehydro-2-methyl-but-1,3-dien-1-yl.porphin
-1378.42864 0.38160
Mg.1,ethynyl.porphin.ethynyl.
-1339.27189 0.34802
Mg.1,1-(cyclopropen-N2-yl)-1-dehydro-methan-1-
yl.porphin -1339.26595 0.35414
Mg.1,1.dehydro-1-(dehydro-cyclopropan-N2-
yl).methan-1-yl.porphin
-1339.21922 0.35564
Mg.1,1-cyclopropen-1-yl-1-dehydro- methan-1-
yl.porphin 14 -1339.23762 0.35108
Mg.1,1-dehydro-1-(1-hydroxy cyclopropan-1-yl)
methan-1-yl.porphin
-1415.59591 0.38333
Mg.1,1-dehydro-2-hydroxy 2-methyl propan 1-
yl.porphin -1416.69175 0.40656
Mg.1,porphin.4-dehydro-2-methyl-but-1,3-dien-N1-
yl. -1378.36221 0.38402
Mg.1,ethynyl.porphin.4-dehydro-2-methyl -but-1,3-
dien-N1-yl.porphin
-1455.44951 0.41583
Mg.1, 4-methen 3-methyl pent-en-1-yl.porphin+
-1457.16216
Mg.1,4-dehydro-3-(1-didehydro methyl)-4-methyl
pent-1-en-N5-yl. porphin
-1455.43205 0.40513
Mg.1,3,4-(1-didehydro methyl) pent-1-en-1-
yl.porphin -1455.33851 0.41918
Mg.1,porphin.3,4-(1-didehydro methyl) pent-1-en-
N1-yl -1455.41199 0.41406
Mg.1,propynyl.porphin.3,4-(1-didehydro methyl)
pent-1-en-N1-yl -1571.60474 0.47722
Mg.1, 5,6-(1-didehydro methyl)-2-methyl-hept-1,3-
dien-1-yl.porphin
-1571.66259 0.47999
Mg.1,porphin.5,6-(1-didehydro methyl)-2-methyl
hept-1,3-dien-1-yl.porphin
-1571.70604 0.48578
Mg.1,ethynyl. porphin.5,6-(1-didehydro methyl)-2-
methyl hept-1,3-dien-1-yl.porphin
-1648.78982 0.50278
Mg.1, 7,8-(1-didehydromethyl)-4-methyl- nonan-
1,3,5-trien-1-yl.porphin
-1648.95251 0.50523
Mg.1,porphin.7,8-(1-didehydromethyl)-4-methyl
nonan-1,3,5-trien-N-1-yl
-1648.76310 0.51924
Mg.1,propynyl. porphin.7,8-(1-didehydromethyl-4-
methyl-) nonan-1,3,5-trien-N-1-yl
-1764.82675 0.57920
Mg.1,7,8-(1-didehydromethyl)-2,4-dimethyl-3-(1-
ethen-N2-yl) nonan-1,5-dien-1-yl.porphin.
-1764.69778 0.58448
.
-
N
Mg N
N
N
C
C
H
CH3
+
-
Mg.porphin.N
+
CH3
HC
C
C
C
H
CH3
+
Mg.porphin.N-
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(17β) Mg.1,2-dehydro-2-methyl -3-(1-dehydro-4,5-
(1-didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porphin
- 1764.82750 0.59997
(17α) Mg.1,2-dehydro-2-methyl -3-(1-dehydro-4,5-
(1-didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porphin
-1764.79592
Mg.1, 2-dehydro-2-methyl-3-(1-dehydro 4-
didehydro methyl 5-methenyl 1-methyl-hex-2-en-1-
yl) cyclopentan-4-en-1-yl).porphin +
-1765.36800
Mg.1, Mg.1, 2-dehydro-2-methyl-3-(4-didehydro
methyl 5-methenyl 1-methyl-hex-2-en-1-yl)
cyclopentan-4-en-1-yl).porphin
-1766.18132
Mg.1, 2-dehydro -2-methyl-3-(1,4,5-trimethyl-hex-
2-en-1-yl) cyclopentan-4-en-1-yl).porphin
-1768.82220 0.66696
Mg.1, 2-dehydro -2-methyl-3-(1,4-dimethyl 5-
methenyl hex-2-en-1-yl) cyclopentan-4-en-1-
yl).porphin -1767.49801
Mg.1,2-dehydro-2-methyl-3-(4,5-(1-
didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porphin+
-1765.21596
Mg.1,2-dehydro -2-methyl-3-(1,5-dimethyl-hex-2-
en-1-yl) cyclopentan-4-en-1-yl).porphin
-1729.66662
Mg.1,2-dehydro -2-methyl-3-(1,5-dimethyl-hexan-
1-yl) cyclopentan-4-en-1-yl).porphin
-1730.92352
Mg.1, porphin.2-dehydro-2-methyl-3-(1,4,5-
trimethy-hex-2-en-1-yl) cyclopentan-4-en-1-yl).
-1768.79265 0.67055
Mg.1,ethynyl porphin.2-dehydro-2-methyl-3-
(1,4,5- trimethyl-hex-2-en-1-yl) cyclopentan-4-en-1-
yl -1845.76098 0.69318
Mg.1, 2-(2-dehydro-1-methyl-5-(1,4,5-trimethyl-
hex-2-en-1yl) cyclopentan-3-en-1-yl) ethen-1-
yl.porphin -1845.89422 0.70258
Mg.1,porphin.2-(2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1yl) cyclopentan-3-en-1-yl)
ethen-N1-yl -1845.87425 0.70534
Mg.1,ethenyl.porphin.2-(2-dehydro-1-methyl-5-
(1,4,5-trimethyl-hex-2-en-1yl)) cyclopentan-3-en-1-
yl) ethen-N1-yl.porphin
-1922.7980 0.73091
Mg.1, 4-(2-dehydro-1-methyl-5-(1,4,5-trimethyl-
hex-2-en-1-yl) cyclopentan-3-en-1-yl) but-1,3-dien-
1-yl.porphin -1922.90934 0.73634
Mg.1,porphin.4-(2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1-yl) cyclopentan-2-dehydro-3-
en-1-yl) but-1,3-dien-N1-yl
-1923.00859 0.73989
Mg.1,ethynyl.porphin.4-(2-dehydro -1-methyl-5-
(1,4,5-trimethyl-hex-2-en-1-yl) cyclopentan-2-
dehydro-3-en-1-yl) but-1,3-dien-N1-yl.porphin
-1999.92482 0.76664
Mg.1,6-( 2-dehydro-1-methyl-5-(1,4,5-trimethy-
hex-2-en-1-yl)) cyclopentan 3-en-1-yl) hex-1,3,5-
trien 1-yl.porphin
-2000.07222 0.769834
Mg.1,6-(2-dehydro 5-isopropyl-1-methyl
cyclopentan-3-en-1yl) hex-1,3,5-trien-1-yl.porphin
(truncated) -1766.26913 0.61111
Mg.1,porphin,6-(2-dehydro 5-isopropyl -1-methyl
cyclopent-3-en-1yl) hex-1,3,5-trien-N1-yl.
-1766.31937 0.61841
Mg.1,porphin.2-(9H-1-isopropyl-8-methyl-inden-4-
yl)-ethen-N1-yl
-1766.44426 0.61390
Mg.1,propynyl.porphin.2-(9H-1-isopropyl-8-
methyl-inden-4-yl)-ethen-N1-yl
-1882.84782 0.68302
Mg.1,2-(9H-4-ethen-N2-yl-1-isopropyl-8-methyl
inden-5-yl )-propen-1-yl.porphin
-1882.84971 0.68687
Mg.1,des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-5-yl.porphin
-1882.91182 0.68680
Mg.1,porphin.des-A-6,7,11,12,15,16-hexa-dehydro-
20-methyl pregnan-5-yl
-1882.88921 0.69071
Mg.1,ethynyl. porphin.des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-N5-yl
-1959.98570 0.71770
Mg.1,2-(des-A-6,7,11,12,15,16-hexa-dehydro-
pregnan-10-yl) ethen-1-yl.porphin
-1960.01249 0.71715
Mg.1,porphin.2-(des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-10-yl) ethen-N1-yl
-1960.04657 0.72534
Mg.1,ethynyl.porphin.2-( des-A-6,7,11,12,15,16-
hexa-dehydro-20-methyl pregnan-10-yl) ethen-N1-
yl -2037.04661 0.76347
Mg.1,4-(des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-10-yl) but-1,3-dien-1-yl.porphin
-2037.14599 0.72348
Mg.1,porphin.4-(des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-10-yl) but-1,3-dien-N4-
yl. -2037.20007 0.76077
Mg.1,porphin 1,2,3,6,7,11,12,15,16-nonan-dehydro-
20-methyl pregnan-4-yl
-2037.18750 0.76422
Mg.1,porphin.3-hydroxy-20-methyl-
1,2,6,7,11,12,15,16-octa-dehydro pregnan-N4-yl)- .
-2112.85520 0.78605
Mg.1,porphin. 2,3,6,7,11,12,15,16-octa-dehydro-1-
hydroxy-20-methyl pregnan-N4-yl)-
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-2112.77831
Mg.1,porphin. 2,6,7,11,12,15,16-heptan-dehydro-
1,3-dihydroxy-20-methyl pregnan-N4-yl)
-2188.26611
Mg.1,porphin. 1,2,5,6,7,8,11,12,15,16-deca-
dehydro-3-hydroxy-20-methyl pregnan-N4-
yl).porphin- 2111.68173 0.75984
1,2,5,6,7,8,11,12,15,16-deca-dehydro-3-hydroxy-
20-methyl pregnane -927.20068 0.48106
1,2,5,6,7,8,11,12,15,16-deca-dehydro-3-hydroxy-
ergostane -1161.00427 0.63789
3-hydroxy ergostane
-1164.52497 0.70995
1,2,10,11,15,16-hexa dehydro ercalciol
-927.15954 0.47842
OH. -75.52257 0.00911
OH- -75.51314 0.00885
H2O -76.19685 0.02298
H2 -1.14414 0.01059
3.2 The Overall Stoichiometry for the
Formation of the Steroid: Ergosterol (D, C,
B, and A Rings).
Although Mg.porphin is here taken as the catalyst
for the reaction, the overall stoichiometry to form
the ergosterol (D, C, B, and A rings) is as follows,
8 H-C ≡ C-H + 4 CH3-C ≡ C-H + H2O + 5 H2 →
C28H44 O
see Fig. 8: (ergosterol) (5)
ΔH = -0.96534 h
The enthalpy change is negative indicating that this
may be the energetically favourable route to the
initial formation of the steroid. The intermediates by
which these stoichiometric reactions may have
occurred are as follows where the first sequence
involves the formation of the D-ring and
substituents to close the C ring.
Mg.porphin + 3 CH3-C ≡ C-H + 6 H-C ≡ C-H +
6H. → Mg.C21H30.porphin
(6)
ΔH = -0.31173 h
The first sequence of reactions is as follows:
where the side-chain is placed in an extended
conformation approaching that of the absolute
configuration of the final product, ergosterol, Fig. 8.
Hydrogenation of intermediates is largely left to the
later stages of the sequence mechanism to allow the
molecule to show its range of reactivity and feasible
products. For clarity, the steroid rings are formed
consecutively, but this is not essential.
Subsections mention variations that may occur for
the prebiotic synthesis of ergosterol and
cholecalciferol (Vitamin D3) and its metabolic
products, 25-hydroxycholecalciferol, and 1,25-
dihydroxy-cholecalciferol, [3]. Chemical equations
are numbered consecutively.
3.3 The Formation of Mg.1,propynyl.
porphin.ethynyl.
With a vacant magnesium coordination site propyne
may form a weak charge transfer complex with
Mg.1,porphin.ethynyl as,
Mg.1,porphin.ethynyl + CH3-C ≡ C- H
Mg.1,propynyl.porphin.ethynyl (7)
ΔH = -0.03204 h
The addition reaction is favourable and the adduct
charges are: ethyne, 0.016, propyne 0.089.
3.4 The Formation of Mg.1, 4-dehydro-2-
methyl-but-1,3-dien-1-yl.porphin
The Mg.1,propynyl.porphin.ethynyl adducts may
coalesce to form a stable complex where some
activation energy is required, as
Mg.1,propynyl.porphin.ethynyl →
Mg.1,4-dehydro-2-methyl-but-1,3-dien-1-yl.porphin
(8)
ΔH = 0.03467 h
The charge on the adduct is 0.165.
-
N
N
N
Mg
N
C
C
H
CH3+C
CH
H
C
C
H
CH3+
C
CH
H
Mg.pophin
-
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At HF accuracy the form of the potential energy
surface showing the excitation required is given in
Fig. 2.
Fig. 2. The potential energy diagram for the
formation of Mg.1,4-dehydro-2-methyl-but-1,3-
dien-1-yl.porphin where the x-axis is C(CH3) –
C(CH) and the y-axis the N(C)-C(H) bond
extension. The Mg.1,propynyl.porphin.ethynyl is at
(2.5,1.5), the bidentate chelate at (1.5,1.5), the
Mg.1,4-dehydro-2-methyl-but-1,3-dien-1-yl.porphin
at (1.5,2.5), the saddle point at (1.7,2.1). The energy
= -1374 + X h.
Fig. 2, is similar to that for the formation of Mg.1,4-
dehydro-pent-1,3-dien-1yl.porphin, [16], [40].
The activation energy to form the adduct was 0.128
h, and to dissociate it was 0.114 h. The enthalpy
changes at HF accuracy being.
ΔH = 0.013 h
3.4.1 The Formation of Mg.1,2-hydroxy-2-methyl
propanyl.porphin.
The synthesis of cholecalciferol (Vitamin D3) has
one less carbon in the side chain, suggesting it is
initially formed by the polymerization on the
catalyst of two ethyne molecules rather than the
ethyne and propyne required for the formation of
ergocalciferol (Vitamin D2). The following set of
reactions postulates how the side chains of
cholecalciferol and 1,25-dihydroxy-cholecalciferol
were originally formed as a variation to the
ergocalciferol synthesis.
3.4.2 The Formation of Mg.1,ethynyl.
porphin.ethynyl.
2 H-C ≡ C-H + Mg.porphin →
Mg.1,ethynyl.porphin.ethynyl (9)
Δ H = -0.01893 h
3.4.3 The Formation of Mg.1, 1-(cyclopropen-N2-
yl)-1-dehydro-methan-1-yl.porphin
Mg.ethynyl.porphin.ethynyl →
Mg.1, 1-(cyclopropen-N2-yl)-1-dehydro-methan-1-
yl.porphin (10)
Δ H = 0.01139 h
Hydrogenation at this point in the synthesis would
give the characteristic side-chain end grouping of
cholecalciferol, -CH2-CH(CH3)2.
3.4.4. The Formation of Mg.1,1.dehydro-1-
(dehydro-cyclopropan-N2-yl).methan-
1yl.porphin
This reaction involves a prototropic transfer as,
Mg.1, 1-cyclopropen-N2-yl-1-dehydro-methan-1-
yl.porphin →
Mg.1,1.dehydro-1-(dehydro-cyclopropan-N2-
yl).methan-1-yl.porphin (11)
Δ H = 0.04806 h
-
N
N
N
Mg
N
C
C
H
H
C
C
H
H
+
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3.4.5. The Formation of Mg.1,1-dehydro-1-
cyclopropen-1-yl methan-1-yl.porphin
This reaction involves a scission of the N-C bond on
excitation as,
Mg.1,1.dehydro-1-(dehydro-cyclopropan-N2-
yl).methan-1-yl.porphin →
Mg.1,1-cyclopropen-1-yl-1-dehydro- methan-1-
yl.porphin (12)
Δ H = -0.02245 h
At this point in the sequence, the adduct may be
fully hydrogenated with molecular hydrogen,
hydrogen ions such as the hydronium ion, or free
radical hydrogen atoms to give the ultimate part of
the D-ring side chain of cholecalciferol as, -CH2-
CH(CH3)2.
3.4.6 The Formation of Mg.1,1-dehydro-1-(1-
hydroxy cyclopropan-1yl) methan-1-yl. porphin
This reaction involves the addition of the elements
of water as,
H2O + Mg.1, 1-cyclopropen-1-yl-1-dehydro-
methan-1-yl.porphin
→
Mg.1,1-dehydro-1-(1-hydroxy cyclopropan-1-yl)
methan-1-yl.porphin (13)
Δ H = -0.14948 h
This hydroxyl substituent occurs in the D-ring of
1,25-dihydroxy-cholecalciferol, the most active
form of cholecalciferol, [3].
3.4.7 The Formation of Mg.1,1-dehydro-2-
hydroxy-2-methyl propan-1-yl.porphin
This reaction is a facile hydrogenation on the
strained cyclopropane ring as,
2H. + Mg.1,1-dehydro-(1-hydroxy cyclopropan-1-
yl) methan-1-yl.porphin →
Mg.1,1-dehydro-2-hydroxy 2-methyl propan- 1-
yl.porphin (14)
Δ H = -0.07870 h
The enthalpy of the reaction strongly suggests that it
is facile with hydrogen free radicals rather than
hydrogen molecules.
This substituent occurs in the D-ring of 1,25-
dihydroxy-cholecalciferol.
3.5 The Formation of Mg.1,porphin.4-
dehydro-2-methyl-but-1,3-dien-N1-yl
The Mg.1,4-dehydro-2-methyl-but-1,3-dien -1-
yl.porphin may be excited by radiation to the higher
energy state, as shown,
Mg.1, 4-dehydro-2-methyl -but-1,3-dien-1-
yl.porphin →
Mg.1,porphin.4-dehydro-2-methyl-but-1,3-dien-N1-
yl (15)
ΔH = 0. 06859 h
The activation energy to form the adduct was the
same as the enthalpy change. Adduct charge = -
0.124.
3.6 The formation of Mg.1,ethynyl. porphin.
4-dehydro-2-methyl but-1,3-dien-N1-
yl.porphin
Mg.1,porphin.4-dehydro-2-methyl -but-1,3-dien-
N1-yl.porphin may add a further ethyne adduct on
the free metal coordination site as,
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H-C ≡ C-H + 4-dehydro-2-methyl-but-1,3-dien-
N1-yl.porphin →
Mg.1,ethynyl.porphin.4-dehydro-2-methyl -but-1,3-
dien-N1-yl.porphin (16)
Δ H = -0.01840 h
Adduct charges were: ethyne, 0.0788, 4-dehydro-2-
methyl but-1,3-dien-N1-yl, -0.142.
3.6.1 The Formation of Mg.1,3-methyl 4-
methene pent-en-1-yl.porphin+
The C2-C3 bond (1.474 Angstrom) of the
Mg.1,ethynyl.porphin.4-dehydro-2-methyl -but-1,3-
dien-N1-yl.porphin, (18), the adduct is slightly
contracted suggesting some double bond character
which might expose the di-radical able to react with
molecular hydrogen without activation energy. The
N-C bond is also liable to scission in the presence of
a proton or other hydrogen species to give a highly
exothermic reaction as,
Mg.1,ethynyl.porphin.4-dehydro-2-methyl -but-1,3-
dien-1-yl.porphin + H2 + H+ →
Mg.1, 4-methen 3-methyl pent-en-1-yl.porphin+
(17)
ΔH(MP2) = -0. 67952 h
However, as there are many favourable
hydrogenation reactions, in this sequence of
reactions hydrogenation is postponed until later to
explore the reactivity of the adducts.
3.7 The Formation of Mg.1,4-dehydro-3-(1-
didehydro methyl)-4-methyl pent-1-en-N5-yl.
porphin.
The two adducts on Mg.1,ethynyl.porphin.4-
dehydro-2-methyl -but-1,3-dien-1-yl.porphin,
(18), may coalesce when excited to form a diradical,
as,
Mg.1,ethynyl. porphin.4-dehydro-2-methyl but-1,3-
dien-N1-yl.porphin →
Mg.1, 4-dehydro-3-(1-didehydro methyl)-4-methyl
pent-1-en-N5-yl.porphin (18)
ΔH = 0.00792 h
Given the opposite charges on the adducts, they are
expected to coalesce where the activation energy
results from an in-plane electronic transition. The
24R was calculated as just 343 cal. below the 24S.
The potential energy surface is given in Fig. 3.
Fig. 3: The form of the potential energy surface for
the bonding of the ethyne and 4-dehydro-2-methyl
but-1,3-diene adducts on the surface of the catalyst
Mg.porphin. The x-axis is the C(H)-C(CH) bond,
and the y-axis is the N(C)-C(H) bond. The initial
reactant is near (2.3,1.6), and the bonded product is
at (1.9,1.5). The saddle point at (2.1,1.5). The N-C
dissociated product at (1.5,2.2), The energy is -1451
+ X h.
-
N
N
N
Mg
N
C
C
H
CH3+
C
CH
H
C
C
H
H
Mg
C
C
H
CH3
C
CH
H
C
C
H
H
.porphin
3
H
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The form of the potential energy surface for the
bonding is presented in Fig. 3. The activation energy
to form the bond was 0.031 h whilst that to open it
was 0.029 h. This is a bi-dentate chelate where the
bond length is 1.9, between the normal single bond
length of 1.54 and the dissociation limit of 2.1
Angstrom. The catalyst has its first excitation
energy largely irrespective of surface adducts at
0.21 h. This is sufficient for the scission of the inter-
adduct bond, the dissociation of the N-C bond, and
the Mg-C bond. For this synthesis, it is assumed that
only the N-C bond is dissociated rendering a greater
entropy for the complex.
The enthalpy change at the HF level was,
ΔH = 0.002 h
The adduct charge was calculated as 0.199.
These di-adducts may give a preferred conformation
as shown in Fig. 4.
Fig. 4: The preferred conformation of Mg.1, 4-
dehydro-3-(1-didehydro methyl)-4-methyl -pent-1-
en-N5-yl.porphin
No extra bonding occurs between the nitrogen-
bonded adduct C2 and the Mg-bonded adduct C2.
This distance is never less than 2.5 Angstrom, well
above the dissociation distance. It is this
conformation which ultimately gives the
configuration of the side chain, C24, in the final
steroid structure, Fig. 11, as 24R or 24S.
The potential energy surface curve showing bonding
of the C3 of the nitrogen-bound adduct at 1.9
Angstrom also suggests the facile formation of C2-
C4 bonding giving Mg.1,ethynyl.porphin. 1-dehydro
2-(cyclopropenyl) where this would ultimately lead
to the formation of the gem-dimethyl groups of the
lanosterol group of steroids if three ethynes (eee)
were initially added instead of epe, [23]. Two added
propyne adducts may also give the characteristic
gem-dimethyl groups, [19].
3.8 The Formation of Mg.1,3,4-(1-didehydro
methyl) pent-1-en-1-yl.porphin
The Mg.1, 4-dehydro-3-(1-didehydro methyl) - 4-
methyl pent-1-en-N5-yl. porphin is liable to
dissociation from the N-pyrrole site with some
activation energy as,
Mg.1, 4-dehydro -3-(1-didehydro methyl) -4-methyl
pent-1-en-N5-yl. porphin →
Mg.1,3,4-(1-didehydro methyl) pent-1-en-1-
yl.porphin (19)
ΔH = 0.10605 h
The activation energy for the C-N dissociation was
calculated at HF as,
ΔH = 0.06 h
The charge on the adduct was -0.039.
3.9 The Formation of Mg.1,porphin.3,4-(1-
didehydro methyl) pent-1-en-N1-yl
The Mg.1,3,4-(1-didehydro methyl) pent-1-en-1-
yl.porphin may be excited to a higher energy state
as,
Mg.1,3,4-(1-didehydro methyl pent-1-en-1-
yl.porphin →
Mg.1,porphin.3,4-(1-didehydro methyl) pent-1-en-
N1-yl (20)
ΔH = - 0.07803 h
The activation energy was the same as the enthalpy
change. The charge on the adduct was -0.441.
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If required, this highly reactive adduct may be
partially hydrogenated as it only requires the close
proximity of a hydrogen molecule for a reaction to
occur with the di-radical without activation energy
in a strongly exothermic reaction.
3.10 The Formation of Mg.1,propynyl.
porphin 3,4-(1-didehydro methyl) pent-1-en-
N1-yl
The Mg.1,porphin.3,4-(1-didehydro methyl) pent-1-
en-N1-yl may add a further propyne adduct on the
vacant magnesium ion site as,
CH3-C ≡ C-H + Mg.1,porphin.3,4-(1-didehydro
methyl) pent-1-en-N1-yl →
\
Mg.1,propynyl.porphin.3,4-(1-didehydro methyl)
pent-1-en-N1-yl (21)
ΔH = 0.05178 h
No activation energy is required to form the charge
transfer adduct. The charge on the adduct was
propyne 0.354, N-adduct -0.477.
3.11 The Formation of Mg.1, 5,6-(1-
didehydro methyl)-2-methyl hept-1,3-dien-1-
yl.porphin.
The Mg.1,propynyl.porphin.3,4-(1-didehydro
methyl) pent-1-en-N1-yl may be excited to coalesce
to form a stable magnesium ion adduct as,
Mg.1,propynyl. porphin.3,4-(1-didehydro methyl)
pent-1-en-N1-yl →
Mg.1, 5,6-(1-didehydro methyl)-2-methyl hept-1,3-
dien-1-yl.porphin. (22)
ΔH = -0.05539 h
The potential energy surface for this bonding is
shown in Fig. 5.
Fig. 5: The form of the potential energy surface for
the bonding of the Mg.1,propynyl. porphin.3,4-(1-
didehydro methyl) pent-1-en-N1-yl adducts on the
surface of the catalyst Mg.porphin. The initial
reactant is near (2.2,1.5), and the product is at
(1.6,1.6). The N-C dissociated product at (1.6,2.2)
The saddle point at (2.1,1.5) The energy is -1567 +
X h.
The activation energy for the transformation was
found to be 0.071 h, whilst the activation energy for
the reverse reaction was 0.107 h. The adduct charge
was -0.475.
These charges may orient the adducts to bond as
shown by the magnetic field of the radiation being
perpendicular to the plane of the porphin and
directed toward the observer. Steric effects are also
determinants, [16], [40].
3.12 The Formation of Mg.1,porphin. 5,6-(1-
didehydro methyl)-2-methyl hept-1,3-dien-1-
yl.porphin
The Mg.1,5,6-(1-didehydro methyl)-2-methyl hept-
1,3-dien-1-yl.porphin may be promoted to the
higher energy N-bound state as,
Mg.1,5,6-(1-didehydro methyl)-2-methyl hept-1,3-
dien-1-yl.porphin →
Mg.1,porphin.5,6-(1-didehydro methyl)-2-methyl
hept-1,3-dien-1-yl.porphin (23)
ΔH = -0.03829 h
-
N
N
N
Mg
N
C
C
H
CH3
+
C
CH
H
C
C
H
H
..
C
C
CH
H
3
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The activation energy is the same as the enthalpy
change.
The charge on the adduct was -0.396
3.13 The Formation of Mg.1,ethynyl.
porphin.5,6-(1-didehydro methyl)-2-methyl
hept-1,3-dien-1-yl.porphin.
Mg.1,porphin.5,6-(1-didehydro methyl)-2-methyl
hept-1,3-dien-1-yl.porphin may accept a further
ethyne adduct as,
H-C ≡ C-H + Mg.1,porphin.5,6-(1-didehydro
methyl)-2-methyl hept-1,3-dien-1-yl.porphin →
Mg.1,ethynyl.porphin.5,6-(1-didehydro methyl)-2-
methyl hept-1,3-dien-1-yl.porphin.
(24)
ΔH = -0.02807 h
The charge on the ethyne was -0.019, and the charge
on the N-entity, -0.235.
3.14 The Formation of Mg.1,7,8-(1-
didehydromethyl)-4-methylnonan-1,3,5-
trien-1-yl.porphin
Ultraviolet light may cause coalescing of the
adducts as,
Mg.1,ethynyl.porphin.5,6-(1-didehydro methyl)-2-
methyl hept-1,3-dien-1-yl.porphin →
Mg.1,7,8-(1-didehydromethyl)-4-methyl nonan-
1,3,5-trien-1-yl.porphin (25)
ΔH = -0.16051
No activation energy was calculated to bond the two
adducts.
The charge on the adduct was 0.289.
3.15 The Formation of Mg.1,porphin.7,8-(1-
didehydromethyl)-4-methyl nonan-1,3,5-
trien-N-1-yl
The Mg.1, 7, 8-(1-didehydromethyl)-4-methyl
nonan-1,3,5-trien-1-yl.porphin may be excited to a
higher energy state as,
Mg.1,7,8-(1-didehydromethyl)-4-methyl nonan-
1,3,5-trien-1-yl.porphin.→
Mg.1,porphin.7,8-(1-didehydromethyl)-4-methyl
nonan-1,3,5-trien-N-1-yl (26)
ΔH = 0.20188 h
The activation energy was the same as the enthalpy
change. Adduct charge was -0.536
3.16 The Formation of Mg.1,propynyl.
porphin.7,8-(1-didehydromethyl)-4-methyl
nonan-1,3,5-trien-N1-yl
The Mg.1, porphin.7,8-(1-didehydromethyl)-4-
methyl nonan-1,3,5-trien-N-1-yl may add a further
propyne as,
CH3-C ≡ C-H + Mg.1,porphin.7,8-(1-
didehydromethyl)-4-methyl nonan-1,3,5-trien-N1-yl
→
Mg.1,propynyl.porphin.7,8-(1-didehydromethyl)-4-
methyl nonan-1,3,5-trien-N1-yl (27)
ΔH = 0.17804 h
The adducts charges were propyne 0.179, N-entity, -
0.567.
-
N
N
N
Mg
N
C
C
H
CH3
+
C
CH
H
CC
H
H
..
C
C
CH
H
3
C
H
C
H
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3.17 The Formation of Mg.1,7,8-(1-
didehydromethyl)-2,4-dimethyl-3-(1-ethen-
N2-yl) nonan-1,5-dien-1yl. porphin.
It is shown that the two adducts may bond as,
Mg.1,propynyl.porphin.7,8-(1-didehydromethyl)-4-
methyl nonan-1,3,5-trien-N1-yl →
Mg.1,7,8-(1-didehydromethyl)-2,4-dimethyl-3-(1-
ethen-N2-yl) nonan-1,5-dien-1yl.porphin.
(28)
Δ H = 0.14467 h
The activation energy at the HF level for the
forward reaction was 0.018 h and for the backward
reaction 0.058 h.
The adduct charge was -0.378.
In this bonding, an asymmetric C3 is formed with
two stereoisomers possible that affect the energies
of the subsequent cyclised cyclopentane derivatives.
At this stage in the sequence of the mechanism, it is
possible for the molecule in an excited state to
cyclise and form the prospective D-ring of the
steroid ergosterol.
3.18 The Formation of Mg.1,2-dehydro-2-
methyl -3-(1-dehydro 4,5-(1-
didehydromethyl)-1-methyl hex-2-en-1-yl)
cyclopentan-4-en-1-yl.porphin
The Mg.1,7,8-(1-didehydromethyl-2,4-dimethyl-3-
(1-ethen-N2-yl)) nonan-1,5-dien-1yl.porphin. may
cyclise with activation as shown,
Mg.1,7,8-di-(1-didehydromethyl)-2,4-dimethyl-3-
(1-ethen-N2-yl) nonan-1,5-dien-1yl.porphin.→
Mg.1,2-dehydro-2-methyl-3-(1-dehydro-4,5-(1-
didehydromethyl)-1-methyl hex-2-en-1-yl)
cyclopentan-4-en-1-yl.porphin (29)
Δ H = -0.11594 h
The activation energy to form the D-ring was 0.04
h, that for the reverse reaction 0.23 h.
The adduct charge was 0.020.
This 17β isomer was calculated as 0.032 h below
that of the 17α isomer (32), establishing the
symmetry of C17.
3.19 The Formation of Mg.1, 2-dehydro-2-
methyl-3-(1,4,5-trimethyl-hex-2-en-1-yl)
cyclopentan-4-en-1-yl).porphin
The Mg.1,2-dehydro-2-methyl -3-(1-dehydro-4,5-
(1-didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porphin may be progressively
hydrogenated to possess a less reactive side-chain.
Just two routes are suggested:
3.19.1 The Formation of Mg.1, 2-dehydro-2-
methyl-3-(1-dehydro 4-didehydro methyl 5-
methenyl 1-methyl-hex-2-en-1-yl) cyclopentan-4-
en-1-yl).porphin
The first involves protonation of side-chain C6
followed by reaction with molecular hydrogen, as,
Mg.1,2-dehydro-2-methyl-3-(1-dehydro-4,5-(1-
didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porpnhin + H+ →
Mg.1, 2-dehydro-2-methyl-3-(1-dehydro 4-
didehydro methyl 5-methenyl 1-methyl-hex-2-en-1-
yl) cyclopentan-4-en-1-yl).porphin + (30)
ΔH(MP2) = -0.54050 h
Mg.1, 2-dehydro-2-methyl-3-(1-dehydro-4-
didehydro methyl 5-methenyl 1-methyl-hex-2-en-1-
yl) cyclopentan-4-en-1-yl).porphin+ + H2 → H+ +
-
N
N
N
Mg
N
C
CH
CH3
C
CH
H
CC
H
H
..
C
C
CH
H
3
CH
CH
C
C
C
H
H3
-
+
H
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Mg.1, Mg.1, 2-dehydro-2-methyl-3-(4-didehydro
methyl 5-methenyl 1-methyl-hex-2-en-1-yl)
cyclopentan-4-en-1-yl).porphin (31)
ΔH(MP2) = 0.33082 h
Mg.1, Mg.1, 2-dehydro-2-methyl-3-(4-didehydro
methyl 5-methenyl 1-methyl-hex-2-en-1-yl)
cyclopentan-4-en-1-yl).porphin + 2H2
→ Mg.1, 2-dehydro-2-methyl-3-(1,4,5-trimethyl-
hex-2-en-1-yl) cyclopentan-4-en-1-yl).porphin
(32)
ΔH(MP2) = -0.35255 h
Mg.1, 2-dehydro-2-methyl-3-(1,4-dimethyl-5-
methenyl)-hex-2-en-1-yl) cyclopentan-4-en-1-
yl).porphin, is the intermediate.
3.19.2 The Formation of Mg.1,2-dehydro-2-
methyl-3-(4,5-(1-didehydromethyl)-1-methyl hex-
2-en-1-yl ) cyclopentan-4-en-1-yl.porphin+
The second involves protonation of side-chain C1
followed by reaction with molecular hydrogen, as,
Mg.1,2-dehydro-2-methyl-3-(1-dehydro-4,5-(1-
didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porpnhin + H+ →
Mg.1,2-dehydro-2-methyl-3-(4,5-(1-
didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porphin+ (33)
ΔH(MP2) = -0.38846 h
Mg.1,2-dehydro-2-methyl-3-(4,5-(1-
didehydromethyl)-1-methyl hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porphin+ + H2 → H+ +
Mg.1, 2-dehydro-2-methyl-3-(4-didehydro methyl
5-methenyl 1-methyl-hex-2-en-1-yl) cyclopentan-4-
en-1-yl).porphin (34)
ΔH(MP2) = 0.17878 h
Mg.1, Mg.1, 2-dehydro-2-methyl-3-(4-didehydro
methyl 5-methenyl 1-methyl-hex-2-en-1-yl)
cyclopentan-4-en-1-yl).porphin + 2H2
→ Mg.1, 2-dehydro-2-methyl-3-(1,4,5-trimethyl-
hex-2-en-1-yl) cyclopentan-4-en-1-yl).porphin
(35)
ΔH(MP2) = -0.35260 h
These two routes to the fully hydrogenated side-
chain may be summarized as,
Mg.1,2-dehydro-2-methyl -3-(1-dehydro -4,5-(1-
didehydromethyl)-1-methyl -hex-2-en-1-yl )
cyclopentan-4-en-1-yl.porphin + 3H2 →
Mg.1, 2-dehydro-2-methyl-3-(1,4,5-trimethyl-hex-
2-en-1-yl) cyclopentan-4-en-1-yl).porphin
(36)
Δ H = -0.53091 h
This sum of the reactions is exergonic with
molecular hydrogen or hydrogen radicals and
without activation energy.
-
N
N
N
Mg
N
C
C
H
CH3
+
C
CH
H
CC
H
H
..
C
C
CH
H
3
CH
CH
C
C
C
H
H3
-
+
H
-
N
N
N
Mg
N
C
C
H
CH3
C
CH
H
CC
H
H
C
C
CH
H
3
CH
CH
C
C
C
H
H
3+H
3
3
H
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The charge on the adduct was -0.331.
The 20S isomer was calculated to be 0.031 h below
the 20R isomer establishing the asymmetry of C20.
3.19.3 The Formation of Mg.1, 2-dehydro -2-
methyl-3-(1,5-dimethyl-hex-2-en-1-yl)
cyclopentan-4-en-1-yl).porphin
In the formation of cholecalciferol, the
hydrogenation is presumed to go further displayed
as,
Mg.1, 2-dehydro-2-methyl-3-(1,5-dimethyl-hex-2-
en-1-yl) cyclopentan-4-en-1-yl).porphin + H2
→
Mg.1, 2-dehydro -2-methyl-3-(1,5,-dimethy-hexan-
1-yl) cyclopentan-4-en-1-yl).porphin
(37)
Δ H(MP2) = -0.11276 h
3.20. The Formation of Mg.1, porphin.2-
dehydro -2-methyl-3-(1,4,5-trimethy-hex-2-
en-1-yl) cyclopentan-4-en-1-yl).porphin
The Mg.1, 2-dehydro-2-methyl-3-(1,4,5-trimethy-
hex-2-en-1-yl) cyclopentan-4-en-1-yl).porphin may
be excited to a higher energy state as,
Mg.1, 2-dehydro-2-methyl-3-(1,4,5,-trimethyl-hex-
2-en-1-yl) cyclopentan-4-en-1-yl).porphin →
Mg.1, porphin.2-dehydro-2-methyl-3-(1,4,5,-
trimethyl-hex-2-en-1-yl) cyclopentan-4-en-1-yl
(38)
Δ H = 0.03274 h
The activation energy is the same as the enthalpy
change.
The charge on the adduct was -0.316.
3.21 The Formation of Mg.1,ethynyl
porphin.2-dehydro -2-methyl-3-(1,4,5,-
trimethyl-hex-2-en-1-yl) cyclopentan-4-en-1-
yl
A further ethyne molecule may add as an adduct on
the magnesium ion site as,
Mg.1, porphin.2-dehydro-2-methyl-3-(1,4,5,-
trimethyl-hex-2-en-1-yl) cyclopentan-4-en-1-
yl).porphin + ethyne →
Mg.1,ethynyl porphin.2-dehydro-2-methyl-3-(1,4,5-
trimethyl-hex-2-en-1-yl) cyclopentan-4-en-1-yl
(39)
Δ H = 0.09240 h
The activation energy to form the weakly bonded
van der Waals complex is negligible.
The adduct charges were ethyne -0.225, N-entity -
0.152.
-
N
N
N
Mg
N
C
C
H
CH3
C
H
H
CC
H
H
C
C
CH
H
3
CH
CH
C
C
C
H
H
3+H3
H
-
N
N
N
Mg
N
C
C
H
CH3
CH2
CH2C
C
C
CH
H
3
CH
CH
C
C
C
H
H
3+H3
H
H2
-
N
N
N
Mg
N
C
C
H
CH3
C
CH
H
CC
H
H
C
C
CH
H
3
CH
CH
C
C
C
H
H3+H
3
3
H
-
N
N
N
Mg
N
C
C
H
CH3
C
CH
H
CC
H
H
C
C
CH
H
3
CH
CH
C
C
C
H
H3+H
3
3
H
C
CH
H
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3.22 The Formation Mg.1, 2-(2-dehydro -1-
methyl-5-(1,4,5-trimethyl-hex-2-en-1yl)
cyclopentan-3-en-1-yl) ethen-1-yl.porphin
The adducts may coalesce as,
Mg.1,ethynyl porphin.2-dehydro -2-methyl-3-
(1,4,5-trimethy-hex-2-en-1-yl) cyclopentan-4-en-1-
yl →
Mg.1, 2-(2-dehydro-1-methyl-5-(1,4,5-trimethyl-
hex-2-en-1yl) cyclopentan-3-en-1-yl) ethen-1-
yl.porphin (40)
ΔH = -0.12489 h
Fig. 6: The potential energy surface for the
coalescing of Mg-ion and N-adducts on the catalyst
Mg.porphin. The initial state is at coordinates
(2.4,1,5). The product at (1.5,2.2). The saddle point
at (2.1,2.2). The N-C un-dissociated product at
(1.6,1.6). The energy is -1840 + X h.
The potential energy surface for the coalescing is
presented in Fig. 6. The activation energy at the HF
level for the forward reaction was not found.
The adduct charge was 0.329.
3.23 The Formation of Mg.1,porphin.2-(2-
dehydro-1-methyl-5-(1,4,5-trimethyl-hex-2-
en-1-yl) cyclopentan-3-en-1-yl).ethen-N1-yl.
The Mg.1, 2-(2-dehydro-1-methyl-5-(1,4,5-
trimethy-hex-2-en-1yl) cyclopentan-3-en-1-
yl).ethen-1-yl.porphin may be excited to a higher
energy state as,
Mg.1, 2-(2-dehydro-1-methyl-5-(1,4,5-trimethy-
hex-2-en-1yl) cyclopentan-3-en-1-yl).ethen-1-
yl.porphin →
Mg.1,porphin.2-(2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1yl) cyclopentan-3-en-1-yl)
ethen-N1-yl. (41)
ΔH = 0.02243 h
The activation energy being the same as the
enthalpy change.
The adduct charge was -0.480.
3.24 The Formation of Mg.1,ethenyl.
porphin.2-(2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1yl)) cyclopentan-3-en-1-
yl) ethen-N1-yl.porphin
The Mg.1,porphin.2-(2-dehydro-1-methyl-5-(1,4,5-
trimethy-hex-2-en-1yl) cyclopentan-3-en-1-
yl).ethen-N1-yl may add a further adduct of ethyne
on the vacant magnesium ion site as,
Mg.1,porphin.2-(2-dehydro-1-methyl-3-(1,4,5-
trimethyl-hex-2-en-1yl) cyclopentan-3-en-1-yl)
ethen-N1-yl + H-C ≡ C-H →
-
N
N
N
Mg
N
C
C
H
CH3
C
CH
H
CC
H
H
C
C
CH
H
3
CH
CH
C
C
C
H
H
3
+
H
3
3
H
C
C
H
H
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Mg.1,ethenyl.porphin.2-(2-dehydro-1-methyl-5-
(1,4,5-trimethyl-hex-2-en-1yl)) cyclopentan-3-en-1-
yl) ethen-N1-yl.porphin (42)
ΔH = 0.14779 h
The activation energy is the same as the enthalpy
change.
The charges on the ethyne and N-entity were 0.107
and -0.518, respectively.
3.25 The Formation of Mg.1,4-( 2-dehydro -
1-methyl-5-(1,4,5-trimethyl-hex-2-en-1-yl)
cyclopentan-3-en-1-yl) but-1,3-dien-1-
yl.porphin
The adducts of Mg.1,ethenyl.porphin.2-(2-dehydro-
1-methyl-5-(1,4,5-trimethy-hex-2-en-1yl))
cyclopentan-3-en-1-yl) ethen-N1-yl.porphin may
bond as,
Mg.1,ethenyl.porphin.2-(2-dehydro-1-methyl-5-
(1,4,5-trimethy-hex-2-en-1yl)) cyclopentan-3-en-1-
yl) ethen-N1-yl.porphin →
Mg.1, 4-(2-dehydro-1-methyl-5-(1,4,5-trimethyl-
hex-2-en-1-yl) cyclopentan-3-en-1-yl) but-1,3-dien-
1-yl.porphin (43)
Δ H = -0.11471 h
No activation energy was calculated for this
bonding.
The charge on the adduct was 0.980.
3.26 The Formation of Mg.1,porphin.4-(2-
dehydro-1-methyl-5-(1,4,5-trimethyl-hex-2-
en-1-yl) cyclopentan-3-en-1-yl) but-1,3-dien-
N1-yl.
The Mg.1, 4-( 2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1-yl) cyclopentan-3-en-1-yl)
but-1,3-dien-1-yl.porphin also forms a high energy
state on excitation as,
Mg.1,4-( 2-dehydro-1-methyl-5-(1,4,5-trimethyl-
hex-2-en-1-yl) cyclopentan-3-en-1-yl) but-1,3-dien-
1-yl.porphin →
Mg.1,porphin.4-(2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1-yl) cyclopentan-3-en-1-yl)
but-1,3-dien-N1-yl (44)
ΔH = -0.09609 h
The activation energy is the same as the enthalpy
change.
The charge on the adduct was -0.442.
3.27 The Formation of Mg.1,ethynyl.
porphin.4-(2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1-yl) cyclopentan-3-en-1-
yl)-N1-yl.porphin
A further molecule of ethyne may be added as,
Mg.1,porphin.4-(2-dehydro-1-methyl-5-(1,4,5-
trimethyl-hex-2-en-1-yl) cyclopentan-3-en-1-yl)
but-1,3-dien-1-yl + H-C ≡ C-H →
-
N
N
N
Mg
N
C
C
H
CH3
C
CH
H
CC
H
H
C
C
CH
H
3
CH
CH
C
C
C
H
H
3
+
H
3
3
H
C
C
H
H
C
C
H
H
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Mg.1,ethynyl.porphin.4-(2-dehydro -1-methyl-5-
(1,4,5-trimethyl-hex-2-en-1-yl) cyclopentan-3-en-1-
yl) but-1,3-dien-N1-yl (45)
Δ H = 0.14816 h
No activation energy was recorded for this addition.
The charge on the adduct was ethyne 0.063, N-
entity -0.507.
3.28 The Formation of Mg.1,6-( 2-dehydro-1-
methyl-5-(1,4,5-trimethyl-hex-2-en-1-yl))
cyclopentan-3-en-1-yl) hex-1,3,5-trien 1-yl
The adducts may bond as,
Mg.1,ethynyl.porphin.4-(2-dehydro -1-methyl-5-
(1,4,5-trimethyl-hex-2-en-1-yl) cyclopentan-3-en-1-
yl) but-1,3-dien-N1-yl . →
Mg.1,6-(2-dehydro-1-methyl-5-(1,4,5-trimethyl-
hex-2-en-1-yl)) cyclopentan-3-en-1-yl) hex-1,3,5-
trien 1-yl.porphin
. (46)
ΔH = -0.14456 h
No activation energy was recorded for this reaction.
The charge on the adduct was 0.161.
The sum of all reactions in the sequence mechanism
may be expressed as,
Mg.porphin + 3 CH3-C ≡ C-H + 6 H-C ≡ C-H +
6H. → Mg.C21H30.porphin
ΔH = -0.31173 h
At this point in the reaction sequence, the side chain
was reduced in size to reduce computation time. It is
subsequently assumed that the enthalpy changes
would not be noticeably changed by the effective
truncation of the side chain.
The revised structure of the molecule in an extended
conformation is as depicted (Fig. 7),
Fig. 7: Mg.1,6-(2-dehydro-5-isopropyl-1-methyl
cyclopentan-3-en-1yl) hex-1,3,5-trien-1-yl.porphin
(truncated)
Two further reactions are needed to close the C-ring
with the truncated side-chain, as follows:
3.29 The Formation of Mg.1,porphin.6-(2-
dehydro-5-isopropyl-1-methyl cyclopentan-3-
en-1yl) hex-1,3,5-trien-N1-yl.
The promotion to the higher N-bound state of the
adduct may be represented as,
Mg.1, 6-(2-dehydro-5-isopropyl-1-methyl
cyclopentan-3-en-1yl) hex-1,3,5-trien-1-yl. porphin
(49) →
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Mg.1.porphin.6-(2-dehydro-5-isopropyl-1-methyl
cyclopentan-3-en-1yl) hex-1,3,5-trien-1-yl
. (47)
ΔH = -0.43743 h
The activation energy was the same as the enthalpy
change. The charge on the adduct was -0.29.
3.30. The Formation of Mg.1,porphin.2-(9H-
1-isopropyl-8-methyl-inden-4-yl) ethen-N1-yl
The cyclisation involving the rotations previously
considered, [16], [40], is represented as,
Mg.1,porphin,6-(2-dehydro-5-isopropyl-1-methyl
cyclopentan-3-en-1yl) hex-1,3,5-trien-1-yl →
Mg.1,porphin.2-(9H-1-isopropyl-8-methyl-inden-4-
yl) ethen-N1-yl (48)
ΔH = -0.12890 h
The activation energy involves rotations, [16], [40],
and the charge on the adduct was -0.34. The closure
of this C-ring determines the trans C-D rings and the
steroid β-methyl substituent at C-13.
This sequence produces the D and C rings of
ergosterol, Fig. 8.
Fig. 8: ergosterol.
3.31 The Formation of Mg.1,propynyl.
porphin.2-(9H-1-isopropyl-8-methyl-inden-4-
yl) ethen-N1-yl
The Mg.1,porphin.2-(9H-1-isopropyl-8-methyl-
inden-4-yl)-ethen-N1-yl may add a further propyne
molecule on the vacant magnesium site as,
propyne + Mg.1,porphin.2-(9H-1-isopropyl-8-
methyl-inden-4-yl) ethen-N1-yl. →
Mg.1,propynyl.porphin.2-(9H-1-isopropyl-8-
methyl-inden-4-yl) ethen-N1-yl (49)
ΔH = -0.15372 h
No activation energy was found for this charge
transfer addition reaction.
The charge on the adducts was: propyne, 0.045, and
the indenyl entity, 0.190.
3.32. The Formation of Mg.1,2-(9H-4-ethen-
N2-yl-1-isopropyl-8-methyl inden-5-yl)
propen-1-yl.porphin.
The Mg.1,propynyl.porphin.2-(9H-1-isopropyl-8-
methyl-inden-4-yl) ethen-N1-yl may cyclise with
the formation of the trans B-C bridge as,
Mg.1,propynyl.porphin.2-(9H-1-isopropyl-8-
methyl-inden-4-yl) ethen-N1-yl →
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Mg.1,2-(9H-4-ethen-N2-yl-1-isopropyl-8-methyl
inden-5-yl ) propen-1-yl.porphin (50)
ΔH = 0.00153 h
The potential energy surface for the bonding is
shown as,
Fig. 9: The potential energy surface showing the
contraction of the C(CH3)-C(H) bond between the
propyne adduct and the N-bound entity as the N-
C(H) bond of the inden-4-yl bond to the porphin
ring is enlarged. The reactant is at (2.6,1.6), the
product at (1.6,1.6). The N-C dissociated product at
(1.6,2.2). The energy is -1882 + X h.
The graph (Fig. 9) does not show any discernable
activation energy for the bonding.
The charge on the adduct was -0.186.
3.33 The Formation of Mg.1,des-A-
6,7,11,12,15,16-hexa-dehydro-20-methyl
pregnan-5-yl.porphin
The Mg.1,2-(9H-4-ethen-N2-yl-1-isopropyl-8-
methyl inden-5-yl ) propen-1-yl.porphin
may cyclise as,
Mg.1,2-(9H-4-ethen-N2-yl-1-isopropyl-8-methyl
inden-5-yl ) propen-1-yl.porphin →
Mg.1,des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-5-yl.porphin (51)
ΔH = -0.06217 h
No activation energy could be recorded during the
scan for this bonding. The charge on the adduct was
0.114
3.34 The Formation of Mg.1,porphin. des-A-
6,7,11,12,15,16-hexa-dehydro-20-methyl
pregnan-5-yl.
The Mg.1,des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-5-yl.porphin may be excited to a
higher energy state as,
Mg.1,des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-5-yl.porphin →
Mg.1,porphin.des-A-6,7,11,12,15,16-hexa-dehydro-
20-methyl pregnan-5-yl. (52)
ΔH = 0.02609 h
The activation energy was the same as the enthalpy
change. The charge on the adduct was 0.34.
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3.35 The Formation of Mg.1,ethynyl.
porphin.des-A-6,7,11,12,15,16-hexa-dehydro-
20-methyl pregnan-N5-yl.
The Mg.1,porphin.des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-5-yl.
may add a further ethyne adduct as,
ethyne + Mg.1,porphin.des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-5-yl.
→
Mg.1,ethynyl. porphin.des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-N5-yl (53)
ΔH = -0.03189 h
No activation energy was recorded for this bonding
addition.
The charge on the ethyne adduct was 0.083, and that
on the phenanthrenyl entity 0.575. These change at
the transition state for the adducts to bond.
3.36 The Formation of Mg.1,2-(des-A-
6,7,11,12,15,16-hexa-dehydro-20-methyl
pregnan-10-yl)-ethen-1-yl.porphin
The Mg.1,ethynyl.porphin.des-A-6,7,11,12,15,16-
hexa-dehydro-20-methyl pregnan-N5-yl. may bond
as,
Mg.1,ethynyl.porphin.des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-N5-yl.
→
Mg.1,2-(des-A-6,7,11,12,15,16-hexa-dehydro-
pregnan-10-yl)-ethen-1-yl.porphin (54)
ΔH = -0.02728 h
The form of the potential energy surface for the
bonding is shown in Fig. 10.
Fig. 10: The reactant is near (3.0,1.5), the product at
(1.6,1.5). The saddle point is near (2.5,1.9). The N-
C dissociated product at (1.5,2.0). The energy is -
1954 + X h.
The activation energy for bonding was 0.03 h, that
for scission, 0.11 h.
The charge on the adduct was 0.053.
3.37 The Formation of Mg.1,porphin.1,2-(
des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-10-yl)-ethen-N1-yl.
Excitation of the Mg.1,2-(des-A-6,7,11,12,15,16-
hexa-dehydro-pregnan-10-yl)-ethen-1-yl.porphin
may lead to severance of the Mg-C bond and
promotion of the adduct to the higher energy state
as,
Mg.1,2-(des-A-6,7,11,12,15,16-hexa-dehydro-
pregnan-10-yl)-ethen-1-yl.porphin →
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Mg.1,porphin.2-(des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-10-yl) ethen-N1-yl.
(55)
ΔH = -0.02678 h
The activation energy was the same as the enthalpy
change. The charge on the adduct was 0.212.
3.38 The Formation Mg.1,ethynyl. porphin.2-
(des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-10-yl)-ethen-1-yl
The Mg.1,porphin.2-(des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-10-yl) ethen-1-yl may
add a further ethyne molecule as,
ethyne + Mg.1,porphin.2-(des-A-6,7,11,12,15,16-
hexa-dehydro-20-methyl pregnan-10-yl) ethen-1-yl
. →
Mg.1,ethynyl.porphin.2-(des-A-6,7,11,12,15,16-
hexa-dehydro-20-methyl pregnan-10-yl) ethen-N1-
yl (56)
ΔH = 0.07456 h
The charge on the ethyne was 0.01, and that on the
phenanthrenyl adduct 0.212.
3.39 The Formation of Mg.1,4-(des-A-
6,7,11,12,15,16-hexa-dehydro-20-methyl
pregnan-10-yl) but-1,3-dien-1-yl.porphin
The Mg.1,ethynyl.porphin. 2-(des-A-
6,7,11,12,15,16-hexa-dehydro-20-methyl pregnan-
10-yl) ethen-N1-yl may bond as,
Mg.1,ethynyl.porphin.2-(des-A-6,7,11,12,15,16-
hexa-dehydro-20-methyl pregnan-10-yl) ethen-N1-
yl →
Mg.1,4-(des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-10-yl) but-1,3-dien-1-yl.porphin
(57)
ΔH = -0.13497 h
The activation energy for bonding was 0.03 h , and
for the reverse reaction 0.11 h. The charge on the
adduct was 0.210.
3.40 The Formation of Mg.1,porphin.4-(des-
A-6,7,11,12,15,16-hexa-dehydro-20-methyl
pregnan-10-yl) but-1,3-dien-N4-yl.porphin
The Mg.1,4-(des-A-6,7,11,12,15,16-hexa-dehydro-
20-methyl pregnan-10-yl) but-1,3-dien-1-yl.porphin
may be promoted to the higher energy state as,
Mg.1,4-(des-A-6,7,11,12,15,16-hexa-dehydro-20-
methyl pregnan-10-yl) but-1,3-dien-1-yl.porphin
→
Mg.1,porphin.4-(des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-10-yl) but-1,3-dien-N4-
yl. (58)
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ΔH = -0.02089 h
The charge on the adduct was 0.231.
3.41 The Formation of Mg.1,porphin. 3-dehydro
1,2,6,7,11,12,15,16-nonan-dehydro-pregnan-4-
y.porphin.
The Mg.1,porphin.4-des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-10-yl) but-1,3-dien-N4-
yl may bond as,
Mg.1,porphin.4-(des-A-6,7,11,12,15,16-hexa-
dehydro-20-methyl pregnan-10-yl) but-1,3-dien-N4-
yl. →
Mg.1,porphin 1,2,3,6,7,11,12,15,16-nonan-dehydro-
20-methyl pregnan-4-yl (59)
ΔH = 0.01564 h
No activation energy to close the ring was recorded
The charge on the adduct was -0.321.
3.42 The Formation of Mg.1,porphin.3-
hydroxy-20-methyl-1,2,6,7,11,12,15,16-octa-
dehydro- pregnan-N4-yl).
The Mg.1,porphin 1,2,3,6,7,11,12,15,16-nonan-
dehydro-20-methyl pregnan-4-yl. maybe
susceptible to reaction with hydroxyl radicals or
anions in the environment, [24], as,
H2O → H+ + OH-1 ΔH = 0.67114 h
H2 → 2H. ΔH = 0.13826 h
Mg.1,porphin 1,2,3,6,7,11,12,15,16-nonan-dehydro-
20-methyl pregnan-4-yl.
+ OH- →
Mg.1,porphin.3-hydroxy-20-methyl
1,2,6,7,11,12,15,16-octa-dehydro-pregnan-N4-yl)-
(60)
ΔH = -0.14300 h
As the molecule is in the excited state then this
reaction is more favourable. The charge on the
adduct was 0.287.
3.42.1 The Formation of Mg.1,porphin.
1,2,6,7,11,12,15,16-octa-dehydro-1-hydroxy-20-
methyl pregnan-4-yl).porphin
In the formation of the cholecalciferol A-ring
substituents, there is an equally facile reaction at the
C3-site with hydroxyl anion, or at the C1 and C3-
sites with hydroxyl radical. This may occur whether
the B-ring forms or not.
Mg.1,porphin 1,2,3,6,7,11,12,15,16-nonan-dehydro-
20-methyl pregnan-4-yl + OH-1 →
Mg.1,porphin. 2,3,6,7,11,12,15,16-octa-dehydro-1-
hydroxy-20-methyl pregnan-N4-yl)-
(61)
ΔH(MP2) = - 0.07767 h
Mg.1,porphin 1,2,3,6,7,11,12,15,16-nonan-dehydro-
20-methyl pregnan-4-yl + 2 OH. →
Mg.1,porphin. 2,6,7,11,12,15,16-heptan-dehydro-
1,3-dihydroxy-20-methyl pregnan-N4-yl
(62)
ΔH(MP2) = - 0.05233 h
3.43. The Formation of Mg.1,porphin.
1,2,5,6,7,8,11,12,15,16-deca-dehydro-3-
hydroxy-20-methyl pregnan-4-yl).porphin-
Mg.1,porphin.1,2,6,7,11,12,15,16-octa-dehydro-3-
hydroxy-20-methyl pregnan-4-yl).porphin- may lose
hydrogen by hydrogen free radical abstraction as,
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Mg.1,porphin.1,2,6,7,11,12,15,16-octa-dehydro-3-
hydroxy-20-methyl pregnan-4-yl).porphin- + 2H..
→ 2H2 +
Mg.1,porphin.1,2,5,6,7,8,11,12,15,16-deca-dehydro-
3-hydroxy-20-methyl pregnan-N4-yl).porphin-
(63)
ΔH = -0.12282 h
The charge on the adduct was 0.700.
This abstraction may alternately operate at the C8
and C9 to form the lanosterol group, [23].
3.44 The Formation of
1,2,5,6,7,8,11,12,15,16-deca-dehydro-3-
hydroxy-20-methyl pregnane
The Mg.1,porphin. 1,2,5,6,7,8,11,12,15,16-deca-
dehydro-3-hydroxy-20-methyl pregnan-N4-
yl).porphin- may react with a proton to release the
adduct from the catalyst as a neutral molecule as,
Mg.1,porphin.1,2,5,6,7,8,11,12,15,16-deca-dehydro-
3-hydroxy-20-methyl pregnan-4-yl).porphin- + H+
→ Mg.porphin +
1,2,5,6,7,8,11,12,15,16-deca-dehydro-3-hydroxy-
20-methyl pregnane (64)
ΔH = -0.62914 h
3.45 The Formation of 1,2,5,6,7,8,11,12,15,
16-deca-dehydro-3-hydroxy-ergostane
At this point in the synthesis with the catalyst
separated, the fully extended side-chain was
restored for the molecule to be depicted as,
Fig. 11: 1,2,5,6,7,8,11,12,15,16-deca-dehydro-3-
hydroxy-ergostane
Further hydrogenation allows the natural substance
to be designated as,
1,2,5,6,7,8,11,12,15,16-deca-dehydro-3-hydroxy-
ergostane + 3H2 →
3-hydroxy-ergostane (65)
ΔH = -0.05264 h
3.46 The Formation ergocalciferol (Vitamin
D2)
The ergosterol may under photolysis give Vitamin
D2, as in the synthetic reaction, [3]. The prebiotic
synthesis may have proceeded similarly.
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Although the B-ring closure is not necessary to form
ergocalciferol, it is assumed here that the B-ring
closed and it is necessary for the scission of the
steroid C9-C10 bond to occur as shown in, Fig. 12,
for the potential energy diagram of Mg.1,porphin.
1,2,5,6,7,8, 11,12,15,16-deca-dehydro-3-hydroxy-
20-methyl pregnan-N4-yl). The potential energy
diagram indicates that the internal coordinates
chosen as stretching of this bond accompanied by a
rotation of the dihedral angle, C5-C6-C7-C8, in the
presence of a hydroxyl anion near a C19 hydrogen
atom. there is a feasible scission of the C9-C10 bond
with an activation energy of 0.15 h, well within the
range of the first excitation of the molecule, 0.24 h.
It also indicates that considerably more activation
energy is required to produce the trans, C5-C6-C7-
C8, isomer. No abstraction of the methyl hydrogen
atom occurs at a hydroxyl anion distance of 1.4 A,
but at 1.0 A, abstraction occurs.
Fig. 12: The potential energy diagram for
Mg.1,porphin.1,2,5,6,7,8, 11,12,15,16-deca-
dehydro-3-hydroxy-20-methyl pregnan-N4-yl). The
y-axis shows the stretching of the C9-C10 bond,
whilst the x-axis shows rotation around the dihedral
angle, C5-C6-C7-C8. The energy is -2180 + X h.
The scission appears also as free radical-mediated
with scission of the C9-C10 bond and contraction of
the C19 hydrogen – C10 coordinate.
The following sequence of reactions appears
feasible after the scission of the C9-C10 bond to
release the catalyst from the ercalciol precursor
(truncated and not fully hydrogenated), Fig. 13, as,
Mg.1,porphin.1,2,5,6,7,8,11,12,15,16-deca-dehydro-
3-hydroxy-20-methyl pregnan-N4-yl).porphin- +
H+ → Mg.porphin +
Fig. 13: 1,2,10,11,15,16-hexa-dehydro ercalciol
(66)
ΔH = -0.59035 h
It is assumed that the above formation of a
dehydrogenated ercalciol, [2], is equivalent to the
formation of ergocalciferol
3.47 The Formation of cholecalciferol (Vitamin
D3)
The reactant for the formation of cholecalciferol is
7-dehydrocholesterol, which differs from ergosterol
in the D-ring side chain being fully hydrogenated
and having one less methyl group replaced by a
hydrogen atom. For the truncated molecules
considered here, the reaction should be similar.
The present-day metabolic products of
cholecalciferol, [3], 25-hydroxycholecalciferol and
1,25-dihydroxycholecalciferol should have all been
freely available at the time of the prebiotic synthesis
of ergocalciferol and cholecalciferol.
4 Conclusion
Steroids have been regarded as composed of
isoprene units, [3], but catalysis suggests that at an
earlier prebiotic time, the isoprene units themselves
may have been formed by the copolymerization of
the interstellar gases ethyne and propyne, inevitably,
according to the laws of chemistry. These are also
both readily available from the reaction of carbides
and allylides in aqueous solution, [25]. The catalyst
used here, Mg.porphin, essential to present
biochemistry, should have enabled the synthesis of
ergosterol at the time of photosynthesis, [26], at
some 3.4 billion years, and vitamin D is recorded in
phytoplankton in the ocean as photosynthesizing
vitamin D for more than 500 million years, [27],
[28]. The catalyst, here taken as Mg.porphin
formed from the same atmosphere, [12], enables
individual steps in the sequence to be activated to a
limit of about 0.21 h, dependent on the radiation
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level present in prebiotic times and the temperature.
It is a surface, photochemically activated catalyst for
a wide range of substrates that only weakly interact
with it as charge transfer or van der Waal
complexes, [21], [22]. It can severely limit the
configurations that are preferentially available to a
growing polymer as here. It provides a plausible
explanation for the three trans bridges: C:D/B:C/A:
B, the steroid C10, C13, and C17 β-substituents, the
3-hydroxyl substituent, the dehydrogenation and the
stereochemistry, where steric effects and charges in
the presence of the exciting magnetic field may have
been determinant.
The very many configurations possible from the
three fused rings allow 23 gross morphological
structures, but these need not be strong contenders
for the vitamin D receptors (VDRs) presently
studied, [29]. Also, the energy change between axial
and equatorial substituents appears minimal, [30].
The production of derivatives that may select
specific enhanced outcomes is considerable, [31],
and several have been approved. It is some
justification for the proposed sequence that the
derivatives involving the 1 and 25 hydroxyl groups
together with the scission of the A-B ring system by
ultraviolet light (UVB), [32], are predicted and
accessible, as is the most stable form of the
ergosterol in the predominantly chair or quasi-chair
conformation, [33].
The formation of the prebiotic steroids essential to
the biochemistry of plants, [34], and mammals, [35],
but not insects, [36], preceded their incorporation
into molecular evolution and biochemistry some 350
million years ago, at least, [37], and their stability
and importance over such a time period are
apparent.
Until the bonding energies of the VDRs are
calculated the alteration and manipulation of the
sequence will be less informed. Mutations, [4], [38]
also affect this on an experimental basis and are a
fruitful field of research. Ab initio studies greatly
augment experimental research and provide a
satisfactory understanding of the prebiotic world.
Further work at a higher accuracy may alter the
values given here.
Acknowledgments:
Appreciation is expressed to Gaussian Corporation.
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Contribution of Individual Authors to the
Creation of a Scientific Article (Ghostwriting
Policy)
Nigel Aylward has written, reviewed, and actively
participated in all the publication stages of this
manuscript.
Sources of Funding for Research Presented in a
Scientific Article or Scientific Article Itself
BMS Education Services Company, Sea Meadow
House, Road Town, Tortola, BRITISH VIRGIN
ISLANDS funded my study.
Conflict of Interest
The author has no conflict of interest to declare that
is relevant to the content of this article.
Creative Commons Attribution License 4.0
(Attribution 4.0 International, CC BY 4.0)
This article is published under the terms of the
Creative Commons Attribution License 4.0
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