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对3-羟基-6-O-甲基红霉素(Ⅳ)的合成进行了研究,可采用3条路线制得。路线1以克拉霉素(Ⅲ)为原料,在稀盐酸中水解脱去克拉定糖制得Ⅳ。该路线中,缩酮化副反应不可避免,w〔半缩酮副产物(Ⅴ)〕=9.3%。该文以克拉霉素的前体2,′4″-O-二(三甲基硅烷基)-6-O-甲基红霉素A 9-O-(1-异丙氧基环己基)肟(Ⅰ)为原料,两步(路线2)或一步(路线3)反应制得Ⅳ。路线2,Ⅳ的总收率为72.8%,w(Ⅳ)=94.8%,w(Ⅴ)<1%;路线3,Ⅳ的收率为81.7%,w(Ⅳ)=93.4%,w(Ⅴ)<1%。这两条路线均可有效地抑制副产物Ⅴ的生成,制得高纯度目标产物Ⅳ,而且都以克拉霉素的前体为原料,可与克拉霉素联产,大大简化了合成工艺,具有产业化前景。
The synthesis of 3-hydroxy-6-O-methylerythromycin (IV) has been studied and can be prepared using three routes. Route 1 to clarithromycin (Ⅲ) as raw materials, in dilute hydrochloric acid hydrolysis stripping sugar system Ⅳ. In this route, the ketalization side reaction is unavoidable and w (hemiketal byproduct (V)] = 9.3%. In this paper, Clarithromycin precursor 2, ’4’ -O-bis (trimethylsilyl) -6-O-methylerythromycin A 9-O- (1-isopropoxycyclohexyl) The total yield of route 2, IV was 72.8%, w (Ⅳ) = 94.8%, w (Ⅴ) <1 (1) %; The yields of route 3 and IV are 81.7%, w (Ⅳ) = 93.4% and w (Ⅴ) <1% respectively. Both of these routes can effectively inhibit the formation of byproduct Ⅴ and produce high purity target product Ⅳ, but also to Clarithromycin precursor as raw material, with clarithromycin co-production, greatly simplifying the synthesis process, with industrialization prospects.