The Biosynthesis of 3‐( trans ‐2‐Nitrocyclopropyl)alanine, a Constituent of the Signal Metabolite Hormaomycin

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)