Taylor James G, Li Xuechen, Oberthür Markus, Zhu Wenjiang, Kahne Daniel E
Department of Chemistry and Chemical Biology, Harvard University, Cambridge, Massachusetts 02138, USA.
J Am Chem Soc. 2006 Nov 29;128(47):15084-5. doi: 10.1021/ja065907x.
Moenomycin A is the only known natural antibiotic that inhibits bacterial cell wall synthesis by binding to the transglycosylases that catalyze formation of the carbohydrate chains of peptidoglycan. We report here the total synthesis of moenomycin A using the sulfoxide glycosylation method. A newly discovered byproduct of sulfoxide reactions was isolated that resulted in substantial loss of the glycosyl acceptor. A general method to suppress this byproduct was introduced, which enabled the glycosylations to proceed efficiently. The inverse addition protocol for sulfoxide glycosylations also proved essential in constructing some of the glycosidic linkages. The synthetic route is flexible and will allow for derivatives to be constructed to further analyze moenomycin A's mechanism of action.
莫能菌素A是唯一已知的天然抗生素,它通过与催化肽聚糖碳水化合物链形成的转糖基酶结合来抑制细菌细胞壁合成。我们在此报告使用亚砜糖基化方法全合成莫能菌素A。分离出一种新发现的亚砜反应副产物,该副产物导致糖基受体大量损失。引入了一种抑制该副产物的通用方法,从而使糖基化反应能够高效进行。亚砜糖基化的反向添加方案在构建一些糖苷键时也被证明是必不可少的。该合成路线具有灵活性,将能够构建衍生物以进一步分析莫能菌素A的作用机制。