新型乳酰亚胺霉素类似物为两栖链霉菌中乳酰亚胺霉素的生物合成提供了见解。
New lactimidomycin congeners shed insight into lactimidomycin biosynthesis in Streptomyces amphibiosporus.
作者信息
Ju Jianhua, Seo Jeong-Woo, Her Yeng, Lim Si-Kyu, Shen Ben
机构信息
Division of Pharmaceutical Sciences, University of Wisconsin National Cooperative Drug Discovery Group, and Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53705-2222, USA.
出版信息
Org Lett. 2007 Dec 6;9(25):5183-6. doi: 10.1021/ol702249g. Epub 2007 Nov 13.
Lactimidomycin (LTM, 1) is a macrolide antitumor antibiotic with a glutarimide side chain from Streptomyces amphibiosporus ATCC53964. To further develop LTM and related analogues as drug candidates we have (i) improved LTM production by approximately 20 fold, (ii) identified three new metabolites (2-4) possibly involved in the LTM biosynthetic pathway; (iii) found 3 to be identical with a previously identified isomigrastatin precursor, (iv) determined the absolute stereochemistry of LTM, and (v) produced new LTM rearrangement products 2a-d and 4a-d.
乳酰亚胺霉素（LTM，1）是一种来自两栖链霉菌ATCC53964的带有戊二酰亚胺侧链的大环内酯类抗肿瘤抗生素。为了进一步开发LTM及其相关类似物作为候选药物，我们已（i）将LTM产量提高了约20倍，（ii）鉴定出三种可能参与LTM生物合成途径的新代谢产物（2 - 4）；（iii）发现化合物3与先前鉴定的异迁移他汀前体相同，（iv）确定了LTM的绝对立体化学结构，以及（v）产生了新的LTM重排产物2a - d和4a - d。
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