A biomimetic domino reaction for the concise synthesis of capreomycidine and epicapreomycidine

Abstract

The non-proteinogenic amino acids capreomycidine and epicapreomycidine are constituents of antibiotically active natural products, but the synthesis of these unusual cyclic guanidine derivatives is challenging. The biosynthesis of capreomycidine has therefore been employed as a guideline to develop a concise biomimetic synthesis of both epimeric amino acids. The resulting domino-guanidinylation-aza-Michael-addition reaction provides the most convenient access to these amino acids in racemic form. Attempts to dissect the domino reaction into two separate transformations for a stereocontrolled version of this synthetic approach have also been made. The synthesized didehydro-arginine derivatives with urethane-protected guanidine moieties did not undergo the aza-Michael-addition anymore. These results may have wider implications for the 1,4-addition of guanidines to α,β-unsaturated carbonyl compounds, particularly to didehydro amino acids.Electronic supplementary materialThe online version of this article (doi:10.1007/s00726-012-1309-8) contains supplementary material, which is available to authorized users.

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

“…Consequently, synthetic routes towards both 3-epimers of 3-hydroxy-L-arginine have been developed which would also enable the preparation of isotopically labelled congeners for biosynthetic studies [ 123 – 124 ]. It should also be noted that a biomimetic domino guanidinylation–aza-Michael-addition reaction for the synthesis of the capreomycidine scaffold has been developed, which only furnished the target structures as stereoisomeric mixtures though [ 125 ].…”

Membrane-interacting properties of the functionalised fatty acid moiety of muraymycin antibiotics

“…Aldehyde 16 was then employed in a sequence of oxime formation (product 17, 92% yield) and reduction to give N-alkyl hydroxylamine 18 (66% yield for the reduction step). As part of our synthetic studies on muraymycins and their analogues, [19][20][21][22][23][24][25][26] we have systematically investigated the preparation of N-alkyl-Nhydroxy-guanidines by guanidinylation 27 of N-alkyl hydroxylamine precursors. 28 A protecting group-free method using guanidinylation reagent 19 turned out to be the best method for this transformation.…”

Muraymycin Nucleoside Antibiotics: Structure-Activity Relationship for Variations in the Nucleoside Unit

“…Synthetic access to the naturally occurring muraymycins is challenging due to structural features such as the non-proteinogenic amino acid L-epicapreomycidine, the aminoribosylated GlyU moiety and the (3S)-3-hydroxy-L-leucine unit. Total syntheses of some naturally occurring muraymycins have been reported though [13,[27][28][29], and synthetic routes towards crucial structural motifs have been developed [30][31][32][33]. Both for potential applications and for more straightforward SAR studies, several simplified muraymycin analogues have been designed [34][35][36][37][38].…”