A Computational Study of a Prebiotic Synthesis of Ergosterol, Ergocalciferol & Cholecalciferol (Vitamin D2 and D3)

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.