2 光学活性な昆虫幼若ホルモン類の合成(口頭発表の部)

抄録

Juvenile Hormones (JH's) have attracted much attention of synthetic chemists since their discovery in 1960's. Only few enantioselective syntheses, however, have been reported because the construction of the epoxide moiety in enantiomerically pure state was difficult. We developed several biochemical conversions to obtain chiral building blocks, and thought that JH's could also be synthesized by utilizing those methods. Herein we describe the syntheses of all known JH's in enantiomerically pure state. As the precursor of the epoxide moiety was chosen the 1,2-diol system, which could be constructed from E by means of ring opening. The alcohol 2a, which could be obtained by baker's yeast reduction of the corresponding diketone, was the starting material of JH III synthesis. The Baeyer-Villiger oxidation of the acetate derived from 2a afforded 3 bearing a hidden 1,2-diol moiety. After the ring opening of 3, its carbon-chain elongation was executed to afford 7. The final step was the formation of the epoxide ring. The use of methanesulfonic anhydride as a mesylating reagent successfully excluded the participation of nucleophilic chloride ion in the reaction mixture, resulting in no racemization at the chiral center to give pure (+)-JH III. The unnatural (-)-JH III could also synthesized from 7. As for other JH's, (+)-2b was required as the common starting material. After screening some yeast strains, Pichia terricola KI 0117 was found to be a suitable one for the selective reduction of 8. By employing the similar procedure as for JH III, (+)-JH 0, I and II were synthesized. The alcohol (+)-2b was successfully converted into (-)-2b, and the synthesis of the unnatural (-)-JH I was also attained. The remaining JH to be synthesized was 4-Me JH I (1e). The additional chiral center was introduced by diastereoselective alkylation of 13 with 11 to afford 14. After several functional group modification, the desired 1e was synthesized. The present samples of both the enantiomers of JH I and JH III were employed for the bioassay, and the results showed that the natural enantiomers show 5,000 to 10,000 times stronger activities than those of unnatural ones.