Ab initio calculations for elucidation of the lanosterol 14 alpha-demethylation mechanism

Abstract

M. Akhtar, I.A. Watkinson, A.D. Rahimtula, D.C. Wilton, K.A. Munday, Biochem. J. 111 (1969) 757-761], and the pathway via intermediate formyloxy proposed by Alexander et al. [K. Alexander, M. Akhtar, R.B. Boar, J.F. McGhie, D.H.R. Barton, J. Chem. Sec. Chem. Commun. (1972) 383-386

R.T. Fischer, J.M. Trzaskos, R.L. Magolda, S.S. Koo, C.S, Brosz, B. Larsen, J. Biol. Chem. 266 (10) (1991) 6124-6132]. We conclude that the formyloxy pathway is more feasible than the carboxylic acid pathway based on an analysis of frontier orbitals, hardness/softness and reactivity parameters. (C) 2000 Elsevier Science B.V. All rights reserved.

Ab initio calculations at the RHF/6-31G level were performed with the SPARTAN program in order to elucidate the best pathway through which norlanosterol could be biosynthesized from lanosterol (demethylation). Two possible main pathways have been reported: the pathway via intermediate carboxylic acid proposed by Olson and Akhtar [J.A. Olson, M. Lindberg, K. Bloch, J. Biol. Chem. 226 (1957) 941-956