32 エリスロノリドAの合成研究

抄録

Erythromycin A (1), produced by the fungus Streptomyces erythreus, is one of the most important compounds among macrolide antibiotics. We now report our recent studies toward the total synthesis of erythronolide A (2), the aglycone of erythromycin A. Stereoselective synthesis of erythro-3-hydroxy-2-alkylpropionates Erythro-3-hydroxy-2-alkylpropionates 13, an important fragment for the synthesis of macrolide antibiotics, were prepared in high stereoselectivity and in high isolated yield by zinc borohydride reduction of the corresponding β-keto esters 10. Stereoselective synthesis of C_8-C_<15> and C_3-C_7 fragments Epoxidation of erythro-hydroxy ester 13e with t-BuOOH-VO(acac)_2 gave the erythro-epoxide 26 exclusively. Subsequent hydrogenation afforded the lactone 28. The ketone 15 corresponding to C_8-C_<15> fragment of erythronolide A (2) was successfully synthesized from the lactone 28, by eight steps: 1) Me_2C(OMe)_2/p-TsOH, 2) LiAlH_4, 3) Ac_2O/Py., 4) DMSO/Ac_2O, 5) K_2CO_3/MeOH, 6) PCC, 7) EtMgBr, 8) PCC. The aldehyde 38 corresponding to C_3-C_7 fragment of 2 was also prepared from β-keto ester 10f in high stereoselectivity.