Stereochemical Elucidation of Streptorubin B
Stereochemical Elucidation of Streptorubin B
复制标题
DOI：
10.1021/ja109164t
复制
发表时间：
2011-02-16
影响因子：
15
通讯作者：
Challis, Gregory L.
中科院分区：
文献类型：
--
作者：
Haynes, Stuart W.;Sydor, Paulina K.;Challis, Gregory L.
链脲菌素B是由几种放线菌（包括模式生物天蓝色链霉菌A3（2））产生的抗生素前体组中结构显著的成员。该分子的吡咯并凡结构内的跨环张力导致限制性旋转，这产生（非对映异构体）阻转异构体的可能性。链脲菌素B的相对和绝对立体化学都是未知的。NOESY NMR实验用于确定链脲菌素B中心点HCl在溶液中的主要阻转异构体的相对立体化学。我们利用了这一发现与我们的知识链脲菌素B生物合成的S。以确定反阻转异构体的绝对立体化学。2-合成了在C-4'位立体选择性标记氘的十一烷基吡咯，并将其用于S. coelicolor，其不能产生链脲菌素B，因为它在2-十一烷基吡咯生物合成中被阻断，并且其中负责链脲菌素B生物合成的最后两个步骤的基因过表达。通过这种突变合成策略产生的立体选择性氘标记的链脲菌素B中心点HCl的H-1和H-2 NMR分析使我们能够将主要（反）阻转异构体的绝对立体化学指定为7'S。链脲菌素B的HPLC分析。coelicolor在纯手性固定相上的分离和与来自对映选择性合成的链脲菌素B的比较表明，天然产物由（7'S，反式）、（7'S，顺式）和（7 'R，反式）立体异构体的约88：7：5的混合物组成。
Streptorubin B is a structurally remarkable member of the prodiginine group of antibiotics produced by several actinobacteria, including the model organism Streptomyces coelicolor A3(2). Transannular strain within the pyrrolophane structure of this molecule causes restricted rotation that gives rise to the possibility of (diastereomeric) atropisomers. Neither the relative nor the absolute stereochemistry of streptorubin B is known. NOESY NMR experiments were used to define the relative stereochemistry of the major atropisomer of streptorubin B center dot HCl in solution as anti. We exploited this finding together with our knowledge of streptorubin B biosynthesis in S. coelicolor to determine the absolute stereochemistry of the anti atropisomer. 2-Undecylpyrrole stereoselectively labeled with deuterium at C-4' was synthesized and fed to a mutant of S. coelicolor, which was unable to produce streptorubin B because it was blocked in 2-undecylpyrrole biosynthesis, and in which the genes responsible for the last two steps of streptorubin B biosynthesis were overexpressed. H-1 and H-2 NMR analysis of the stereoselectively deuterium-labeled streptorubin B center dot HCl produced by this mutasynthesis strategy allowed us to assign the absolute stereochemistry of the major (anti) atropisomer as 7'S. HPLC analyses of streptorubin B isolated from S. coelicolor on a homochiral stationary phase and comparisons with streptorubin B derived from an enantioselective synthesis showed that the natural product consists of an approximately 88:7:5 mixture of the (7'S, anti), (7'S, syn), and (7'R, anti) stereoisomers.