Original scientific paper

Mechanism of 1,2-Hydride Shift in Some Carbocations Involved in Steroid Biosynthesis

Valerije Vrček orcid.org/0000-0003-1624-8126 ; Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Ivana Vinković Vrček orcid.org/0000-0003-1382-5581 ; Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia
Olga Kronja ; Faculty of Pharmacy and Biochemistry, University of Zagreb, A. Kovačića 1, 10000 Zagreb, Croatia

Abstract

The mechanism of 1,2-hydride shift in protosteryl C(20) cation (1A) and in dammarenyl C(20) cation (2A) was investigated by the semi-empirical AM1 method and ab initio quantum Chemical calculations (HF/3-21G level). Stationary points 1A/1B and 2A/2B, and the corresponding transition hydrido-bridged structures 1TS and 2TS were located on the energy surface. Process 1A→1B turned out to be energetically more favorable than process 2A→2B by ca. 9 kcal mol-1, mostly due to the unfavorable steric repulsive interaction between the methyl group at C(14) and the β-oriented side chain at C(17) in 1A and the lack of CC-hyperconjugative stabilization in 1A. The exothermicity of processes 1A→1B and 2A→2B was increased by subsequent introduction of substituents (H, Me, i-Pr, and t-Bu) at C(14). The more pronounced trend in 1A→1B proves that the origin of the relative stability of 1B comes from the steric interactions in 1A. Introduction of the halogen atom (F, Cl, and Br), due to its -I effect and relatively small size, changed the direction of the equilibrium 1A_Y/1B_Y, and 1A_Y was found to be by ca. 3 kcal mol-1 more stable than 1B_Y.

Keywords

steroid biosynthesis; quantum-chemical calculations; carbocations; hydride shift

Hrčak ID:

131956

URI

https://hrcak.srce.hr/131956

Publication date:

1.11.2001.

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