42 (+)-ストレプタゾリンの全合成(口頭発表の部)

抄録

Streptazolin (1), originally discovered in 1981 from cultures of Streptomyces viridochromogenes, has the striking structural feature of an unusual ring system 2-azabicyclo[4.3.0]nonane (pyrindine) and an internal urethane unit both rarely distributed in nature. The isolation and characterization of this antibiotic were complicated by its tendency to undergo polymerization in concentrated form due to the presence of the conjugated diene part. We present the stereoselective synthesis of (+)-streptazolin (1) and (-)-4a,5-dihydrostreptazolin (5) by a new strategy utilizing a palladium-based approach under the nonreductive and reductive conditions, respectively, for constructing the pyrindine core skeleton bearing the Z ethylidene group. The chiral imide 21 was converted to the enyne compound 29 via N-acyliminium ion cyclization of the acetoxy lactam 25, partial reduction of 26 with DIBALH-BuLi, and formation of the dibromoolefin 28. Subsequent removal of the benzyl protecting group followed by basic treatment provided the cyclic carbamate 31, which was subjected to palladium(II)-catalyzed cyclization under the reductive conditions using polymethylhydrosiloxane as a hydride source to afford (-)-4a,5-dihydrostreptazolin (5). On the other hand, palladium-catalyzed cyclization of 31 under the nonreductive conditions led to the formation of (-)-Δ^5-streptazolin (32). Attempted isomerization of the 1,4-diene system in 32 did not resulted in any of desired streptazolin (1) with 1,3-diene system. We thus turned to the nonreductive cyclization of the bicyclic enyne compound 29. The best result in the palladium-catalyzed bicyclization of 29 was obtained when treated with 30 mol % Pd(OAc)_2 and N,N'-bis(benzylidene)ethylenediamine (BBEDA) as the ligand in benzene at reflux, thus affording a 93: 7 mixture of the 1,2,4a, 6,7,7a-hexahydro-5H-1-pyrindine (Z)-34 along with its isomerized product (Z)-35 in 84% total yield. The isomerization of the 1,4-diene in (Z)-34 to the 1,3-diene was successfully achieved by treatment with triiron dodecacarbonyl to generate the stable tricarbonyl(η^4-1,3-diene)iron complex 36, which was then converted to the glycol 37. Treatment of 37 with sodium methoxide followed by ordinary chromatography on silica gel resulted in isolation of chemically and enantiomerically pure (+)-streptazolin (1).