Total synthesis of narbonolide and biotransformation to pikromycin
Total synthesis of narbonolide and biotransformation to pikromycin
复制标题
DOI：
10.1021/jo062047u
复制
发表时间：
2006-12-22
影响因子：
3.6
通讯作者：
Fecik, Robert A.
中科院分区：
文献类型：
--
作者：
Venkatraman, Lakshmanan;Salomon, Christine E.;Fecik, Robert A.
据报道，改进了纳博内酯的全合成及其生物转化为匹克霉素。该全合成利用分子内 Nozaki-Hiyama-Kishi 偶联，显着提高了大环化产率 (90-96%)，并允许区分 C3 和 C5 氧化态。委内瑞拉链霉菌的 pikAI 缺失突变体用于通过体内糖基化和氧化将合成的纳波内酯生物转化为匹克霉素。合成化学和工程生物转化的结合为合成具有生物学意义的新型大环内酯类似物带来了巨大的希望。
An improved total synthesis of narbonolide and its biotransformation to pikromycin is reported. This total synthesis utilized an intramolecular Nozaki-Hiyama-Kishi coupling that significantly improved macrocyclization yields (90-96%) and allowed for differentiation of the C3- and C5-oxidation states. A pikAI deletion mutant of Streptomyces Venezuelae was used to biotransform synthetic narbonolide to pikromycin by glycosylation and oxidation in vivo. This integration of synthetic chemistry and engineered biotransformations holds great promise for the synthesis of novel macrolide analogues of biological interest.