Thermal atropisomerism of aglucovancomycin derivatives:: Preparation of (M,M,M)- and (P,M,M)-aglucovancomycins
Thermal atropisomerism of aglucovancomycin derivatives:: Preparation of (M,M,M)- and (P,M,M)-aglucovancomycins
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DOI：
10.1021/ja981928i
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发表时间：
1998-09-09
影响因子：
15
通讯作者：
Jin, Q
中科院分区：
文献类型：
--
作者：
Boger, DL;Miyazaki, S;Jin, Q
万古霉素降解为一系列含有关键官能团修饰的葡糖万古霉素衍生物，并研究了它们的热阻转异构性。在所有情况下，在CD和AB立体化学不受影响的条件下观察到DE环系统阻转异构体的选择性异构。观察到CD和DE环系统的竞争性逆羟醛环裂解（CD > DE），但可以通过选择溶剂和热条件（DE环系统）来最小化或通过醇保护（CD环系统）来排除。类似地，通过从Asn残基损失氨而形成的竞争性主链琥珀酰亚胺可以通过选择热条件来最小化或通过羧酰胺保护来防止。本文报道了天然葡万古霉素（M，M，M）-2及其非天然DE阻转异构体（P，M，III）-2的再合成。公开了关键衍生物及其非天然DE环系统P-非对映异构体的比较抗微生物活性。
The degradation of vancomycin to a series of aglucovancomycin derivatives containing modifications in key functional groups and a study of their thermal atropisomerism are detailed. In all of the cases, selective isomerism of the DE ring system atropisomers was observed under conditions where the CD and AB stereochemistries were unaffected. Competitive retro aldol ring cleavage of the CD and DE ring systems (CD > DE) was observed but could be minimized by the choice of solvent and thermal conditions (DE ring system) or precluded by alcohol protection (CD ring system). Similarly, competitive main chain succinimide formation through the loss of ammonia from the Asn residue could be minimized by the choice of thermal conditions or prevented by carboxamide protection. Resynthesis of natural aglucovancomycin, (M,M,M)-2, and its unnatural DE atropisomer (P,M,III)-2 from 6 are described. The comparative antimicrobial activity of the key derivatives and their unnatural DE ring system P-diastereomers are disclosed.