A new mechanistic scenario for the photochemical transformation of ergosterol: an MC-SCF and MM-VB [molecular mechanics-VB] study

The photochemical reaction network and photoequilibrium involved in the commercial synthesis of vitamin D and centered on ergosterol, precalciferol, lumisterol, tachysterol, and the toxisterols obtained by overirradiation have been studied using MM-VB. The six active electrons of the 1,3,5-hexatriene moiety are treated quantum mechanically via valence bond theory VB, and the remainder of the molecule is treated via molecular mechanics, MM. The results are then confirmed on the model system 1,3,5-hexatriene using MC-SCF computations at the 4-3 IG level with a CAS space of six orbitals and six electrons. A general mechanistic scenario that focuses on precalciferol as the hub of the photochemical reaction network and photoequilibrium has been documented. The central feature of this scenario is the existence of three 'structural bottlenecks' through which the excited-state system must pass in order to return to the ground state. These structural bottlenecks are conical intersections or actual crossings of the ground and excited states where a fully efficient radiationless decay from the excited state to the ground state becomes possible. The optimized molecular structures at the conical intersections contain an integral allyl system located along the centers C2-C3-C4 of the hexatriene moiety in two of the conical intersection structures and along the centers C4-C5-C6 in the third. In both cases the carbon frame centered on the remaining carbon centers of the hexatriene moiety (i.e., C1, C4, and C5 in one case and C1, C2, and C3 in the other) is twisted or pyramidalized in such a way that the three sp hybrid orbitals are virtually orthogonal to each other and to the allylic system. These structures can be described as tetraradicaloid with three localized unpaired electrons and a fourth delocalized unpaired electron in an quasi-planar allyl-like fragment. The occurrence of the many different photorearrangement products in the precalciferol reaction network is completely rationalized by the many possible spin recouplings that can occur in this tetraradicaloid as it emerges on the ground-state surface at the conical intersection. Thus the main branches of the ergosterol photochemistry (leading to lumisterol and tachysterols) are based upon pathways involving the passage through these conical intersections.