Carboxylic acid-mediated, epoxide-initiated cation-olefin cyclizations and 'A-ring' formation in sterol biosynthesis

This thesis describes a mechanistic study to determine whether epoxide-initiated cation-olefin cyclization of oxiranes such as 2 proceeds via (1) rate-determining proteolysis of the oxirane to generate the C(2) cation followed by electrophilic attack of this cation on the nearest olefin, or (2) concerted oxirane cleavage and cyclization via nucleophilic attack of the olefin on the protonated oxirane. Kinetic measurements and product distributions(DIAGRAM, TABLE OR GRAPHIC OMITTED...PLEASE SEE DAI) from the reactions of substrates 1 - 6 with chloroacetic and trichloroacetic acids in deuteriochloroform solution revealed that in the reaction of 1, which cannot undergo cyclization, the major product (77%) is the 2-hydroxy-2-methyl-3-chloroacetyloctane. The reaction was found to be second-order in acid and third-order overall, which is a marker for an S;These results are consistent with a mechanism which involves participation of a nucleophile in the ring-opening of the protonated oxirane, i.e., oxirane cleavage and cyclization are concerted. They also reflect observations made regarding the enzymic cyclization of 2,3-oxidosqualene (7) to lanosterol, for which evidence has been found to support a synchronous pathway of oxirane cleavage and cyclization in A-ring formation.