Ab initio MO study on the difference of solvent effect between exo and endo stereoisomers of aflatoxin B_1 8,9-oxide for S_N2 type nucleophilic ring opening

摘要

Ab initio MO calculation was performed to study the solvent effect for S_N2 type nucleophilic oxirane ring opening of Aflatoxin B_1 8,9-oxide (1) by using model compounds, (1aS, 2aS, 5aR, 5bR)-1a, 2a, 5a, 5b-tetrahydrofuro[2,3-b]oxireno[2,3-d]furan (I) and (1aR, 2aS, 5aR, 5bS)-1a, 2a, 5a, 5b-tetrahydrofuro[2,3-b]oxireno[2,3-d]furan (II). H_2O was considered to be the coordinating molecule 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) In the reaction of I, H_2O molecules can coordinate to oxirane oxygen with little steric congestion, however, TSs for the reaction of II surfaces severe steric congestion for solvation. (2) four the reaction of II, approach of solvating H_2O molecules to oxirane oxygen is sterically restricted to occur from only three directions (outside, backside, and frontside). Consequently, solvation must be accompanied with unfavorable reorganization of stabile hydrogen bonding network in H_2O solvent. (3) The energy difference between the most stable exo and endo-attacking TS tends to increase as the number (n = 0 - 3) of coordinating H_2O increases. These calculational results suggest that solvent effect clearly makes endo-attacking of nucleophile predominant.