Hormaomycin analogues by precursor-directed biosynthesis -: Synthesis of and feeding experiments with amino acids related to the unique 3-(trans-2′-nitrocyclopropyl)alanine constituent

被引：18

作者：

Kozhushkov, SI ^{[1
]}

Zlatopolskiy, BD ^{[1
]}

Brandl, M ^{[1
]}

Alvermann, P ^{[1
]}

Radzom, M ^{[1
]}

Geers, B ^{[1
]}

de Meijere, A ^{[1
]}

Zeeck, A ^{[1
]}

机构：

[1] Univ Gottingen, Inst Organ & Biomol Chem, D-37077 Gottingen, Germany

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2005年 / 2005卷 / 05期

关键词：

aldol reactions; amino acids; biosynthesis; hormaomycin; isotopic labeling; natural products; synthetic methods;

D O I：

10.1002/ejoc.200400608

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The deuterium-labeled racemic 3-(trans-2'-nitrocyclopropyl)alanine (rac-[D-2]-3) and 3-(trans-2'-aminocyclopropyl)alanine (rac-[D-2]4) as well as non-labeled rac-3-[trans-2-(hydroxycarbonyl)cyclopropyl]alanine (rac-5a) and rac-3-[trans-2-(methoxycarbonyl)cyclopropyl]alanine (rac-5b) were prepared in 43, 18, 88 and 49% overall yield, respectively, along a general synthetic route applying alkylations of the lithium enolate of tert-butyl (diphenylmethylene)aminoacetate (O'Donnel's glycine equivalent 11) as a key step. Feeding experiments with these amino acids and Streptomyces griseoflavus (strain W 384) revealed that rac-[D-2]-3, rac-5a and rac-5b are incorporated to give hormaomycin 1b and its analogue 23, respectively, while rac-[D-2]-4 is not. Feeding of rac-2-(trans-2'-nitrocyclopropyl)glycine (rac-6) unexpectedly gave the 5-nitronorvaline-containing hormaomycin analogues 25a-c. This is rationalized as arising from a cyclopropyl to homoallyl anion rearrangement followed by enzymatic hydrogenation of the double bond. These experiments provided new insights into the substrate specificity of the enzyme which assembles hormaomycin. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).

引用

页码：854 / 863

页数：10

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