45 30員環ポリエンマクロライド抗生物質ロキサチシンの全合成(口頭発表の部)

抄録

The total synthesis of the polyene macrolide antibiotic roxaticin (1) is reported. Roxaticin is an oxo pentaene macrolide isolated from an unidentified streptomycete strain similar to Streptomycetes ruber and shows antifungal activity. The stereostructure was determined by X-ray crystal analysis, which revealed the presence of an alternating polyol chain containing both syn and anti-1,3-diol units. The polyol fragment was prepared by a three-fold convergent route. The optically pure building blocks 10 and (R)-and (S)-11 were prepared from (S)-malic acid and (S)-and (R)-glycidol, respectively. These chiral building blocks were assembled efficiently in a reiterative manner which included dithiane-epoxide coupling and 1,3-asymmetric reduction to give the protected polyol 28. Selective manipulation of the terminal 1,2-diol unit protected with diphenylmethylene ketal yielded the aldehyde 3. The small fragment 2 was prepared by the Evans' asymmetric aldol reaction. The Julia coupling reaction of 2 with 3 gave the polyol fragment 37, which was transformed into hydroxy aldehyde 39. The Wittig-Horner reaction of tetraene ester 4 and 39 provided the protected seco-ester 40. The macrocyclic ring was closed by lactonization using the Yamaguchi-Yonemitsu method, and acid-catalyzed deprotection completed the synthesis of roxaticin.