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The Biosynthesis of 3‐( trans ‐2‐Nitrocyclopropyl)alanine, a Constituent of the Signal Metabolite Hormaomycin
Author(s) -
Brandl Melanie,
Kozhushkov Sergei I.,
Zlatopolskiy Boris D.,
Alvermann Petra,
Geers Bernadette,
Zeeck Axel,
de Meijere Armin
Publication year - 2005
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200400493
Subject(s) - chemistry , stereochemistry , yield (engineering) , alanine , lithium diisopropylamide , lysine , alkylation , amino acid , metabolite , organic chemistry , deprotonation , biochemistry , ion , materials science , metallurgy , catalysis
Feeding experiments with Streptomyces griseoflavus using deuterium‐labeled racemic 3,3‐[D 2 ]‐ ( 6b ), 4,4‐[D 2 ]‐ ( 6c ), 5,5‐[D 2 ]‐ ( 6d ), and 6,6‐[D 2 ]‐lysine ( 6e ), and 3‐amino‐5‐(2‐amino‐1,1‐dideuterioethyl)‐4,5‐dihydrofuran‐2‐one dihydrochloride ( 34· 2HCl) were carried out in order to obtain detailed information about the hitherto unknown biosynthetic pathway from lysine to the unusual amino acid 3‐( trans ‐2′‐nitrocyclopropyl)alanine [(3‐Ncp)Ala] ( 2 ), which is a building block of hormaomycin 1a . The corresponding lysine dihydrochlorides were prepared in 33, 24, 19, and 30% overall yield, respectively, along a new efficient general synthetic route applying an alkylation of the lithium enolate of O′Donnel’s glycine equivalent 7 as a key step. In the attempted preparation of 5,5‐[D 2 ]‐4‐hydroxylysine ( 29 ), the respective γ‐lactone ( 34· 2 HCl) was obtained in five steps with 10% overall yield. The distribution of isotope labels in hormaomycins 1b − d led to the formulation of a reasonable cyclization mechanism of 2‐amino‐4‐hydroxy‐6‐(hydroxyimino)hexanoic acid, an ψ‐oxime analogue of 4‐hydroxylysine. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)