Based upon the idea of the stepwise mechanism of biomimetic olefin cyclimtion and enzymatic cyclization of oxidosqualene via conformationally flexible cationic intermediates, significant attention has been focused on each step of sterol biosynthesis. Today, the biosyntheses of phytosterols such as dammaranoid, lupanoid, oleananoid, and tirucallanoid are explained by the cyclization of oxidosqualene via a bicyclic cation 1, tricyclic 6/6/5-cation (pre-C ring cation) 2, secondary 6/6/6-cation 3, and 6/6/6/5 cation 4. In the animal kingdom, steroids are also constructed through the corresponding boat-form B-ring intermediates. Transformation of 1 to 2 is selective cyclization to 6/5 trans fused system even though 6/5 cis is generally more stable. Transformation of 2 to 3 involves ring expansion of a tertiary cationic substrate into a secondary cation, namely, an anti-Markovnikov cation. We have investigated the possibilities of the transformations of 1 to 2 and 2 to 3 as a chemical reaction by preparing model cations. When bicyclic tert-alcohol 8 was treated with BF_3 ・Et_2O, 6/6/5-tricyclic compound 10 and 11 were formed and the structures were confirmed by X-ray analysis. Thus the trans selective 6/5 cyclization took place via cation 12. Now we will be able to state that 6/5 trans selective cyclization from 1 to 2 does not depend upon any special enzyme effect. This may be due to the steric repulsion between the angular methyl and C-12 and C-13 methylenes for 6/5 cis cyclization as illustrated in 13. Next problem to be solved is the Markovnikov' wall. We chose a diol 18 as the model compound and investigated the chemical behavior of the generated cation 19. Most of the Lewis acids such as BF_3・Et_2O, SnCl_4, Sc(OTf)_3, FeCl_3, or TiF_4, and CF_3SO_3H leads to a hydride shift to cation 20 leading spiro cyclic ether 21. This hydride shift corresponds to the initiation of the backbone rearrangement on the D-ring of steroid On the other hand, TiCl_4, selectively induces rearrangement to secondary cation 22 by the ring expansion that corresponds to the C-ring formation of sterol biosynthesis, and afforded cis-ether 23, along with chlorides 24 and 25. AlCl_3 and ZrCl_4 induce further rearrangement into six-membered ring tert-cation 29 and afforded only isomeric cis-ether 26. Thus, the transformation of 2 to 3 will also be able to achieve without enzyme.
