Theoretical Study on the Solvent Effect for SN2 Type Oxirane Ring Opening of exo- and endo-Aflatoxin B1 8,9-Oxide

Toshiya OKAJIMA* and Akane HASHIKAWA

Department of Chemistry, Faculty of Culture and Education, Saga University; 1 Honjo-machi, Saga-shi 840-8502 Japan

Ab initio MO Calculation was performed to study the solvent effect for SN2 type nucleophilic oxirane ring opening of aflatoxin B1 8,9-oxide by using model compounds, (2S, 3R, 3aR, 6aS)-3a, 6a-dihydrofuro[2,3-b]furan 2,3-oxide (I) and (2R, 3S, 3aR, 6aS)-3a, 6a-dihydrofuro[2,3-b]furan 2,3-oxide (II). H2O molecules were considered for the solvation to oxirane oxygen, on which negative charge grows as the reaction proceeds. Stationary points including transition structures (TSs) were optimized with no geometrical constraint at the RHF/3-21G basis set. Relative energies were evaluated at Becke3LYP/3-21G level based on the RHF/3-21G geometries.
Calculation clarified the following points:
(1) Although H2O molecules can coordinate to oxirane oxygen without steric congestion for the reaction of I, II suffers severe steric repulsion between coordinating H2O molecules and the fused dihydrofuran moiety. On the basis of the model study, experimentally observed higher reactivity of exo isomer of AFB1 oxide than endo for nucleophilic reactions can be explained by the difference of solvent effect between them.
(2) For the reaction of II, coordination of H2O molecules to oxirane oxygen is limited to occur from only three directions (outside, backside, and inside). Judging from the energetics of single and two H2O coordinating systems, coordinating capability of H2O to oxirane oxygen (that is, stabilizing ability of TS) is in the order of outside>backside>inside coordination, implying that the steric repulsion between H2O and AFB1 unit is in the order of outside<backside<inside.
(3) The energy difference between the most stable exo- and endo-attacking TS tends to increase as the number of coordinating H2O (n value) increases, clearly suggesting that solvent effect makes endo-oxirane (I) much more reactive for nucleophilic ring opening reaction.
(4) In the reaction of I, the activation energies drastically became small as the number of coordinating H2O to oxirane oxygen increases. On the other hand, in the reaction of II activation energy for three-H2O coordinating system became larger than that for two H2O coordinating system, which is attributable to the steric congestion between B ring and solvating H2O to oxirane oxygen.

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