Ab initio MO study on the difference of solvent effect between exo and endo stereoisomers of aflatoxin B-1 8,9-oxide for S(N)2 type nucleophilic ringopening

Ab initio MO calculation was performed to study the solvent effect for S(N) 2 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-tetrahydrofuror[ 2,3-b]oxireno [2,3-d]furan (I) and (1aR, 2aS, 5aR, 2bS)-1a, 2a, 5a, 5b-tetr ahydrofuro[2,3-b]oxireno [2,3-d]furan (ZI). H2O was considered to be the co ordinating molecule to oxirane oxygen, on which negative charge grows as th e 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 re action of I, H2O molecules can coordinate to oxirane oxygen with little ste ric congestion, however, TSs for the reaction of II suffers severe steric c ongestion for solvation. (2) For the reaction of TI, approach of solvating H2O molecules to oxirane oxygen is sterically restricted to occur from only three directions (outside, backside, and frontside). Consequently, solvati on must be accompanied with unfavorable reorganization of stable hydrogen b onding network in H2O solvent. (3) The energy difference between the most s table exo and endo-attacking TS tends to increase as the number (n = 0-3) o f coordinating H2O increases. These calculational results suggest that solv ent effect clearly makes endo-attacking of nucleophile predominant. (C) 200 0 Elsevier Science B.V. All rights reserved.