Synthesis of an advanced intermediate of alfa-alloenduracididine from allylglycine

Abstract

α-Alloenduracididine, 3-(2-amino-4,5-dihydro-1Himidazole-4-yl)-2-aminopropionic acid)1 and its diastereoisomer, enduracididine 2, are two nonproteinogenic amino acids isolated in 1968 from Streptomyces fungicidicus as part of a cyclopeptide the enduracidine, which has antibiotic activity.1,2 α-Alloenduracididine, which can be viewed as a constrained analogue of arginine,3 belongs to a family of natural amino acids having the terminal guanidine nitrogen atom linked to the methylene backbone. Most of these amino acids are components of peptide antibiotics isolated from extracts of microorganisms and include: β-hydroxyenduracididine and β-hydroxyalloenduracididine (constituents of (α-ε)-mannopeptimycins),3 tetrahydrolathyrine, capreomycidine (constituent of capreomycins). Our laboratory has recently completed the first total synthesis and determination the absolute configuration of tetrahydrolathyrine.4 Here, we described an efficient synthetic route to acess the α-alloenduracididine by synthesis of an advanced intermediate amino alcohol 11, obtained as diastereoisomers mixture (11a and 11b). Amino alcohol intermediate was synthesized, in eight steps, from ethyl (R)-N-Boc-allylglycinate 4 in satisfactory yields from 4. Studies concerning the oxidation of the amino alcohol to the amino acid and determination of the absolute configuration at C4 of each diastereoisomer are in progress.

Keywords

• amino acids
• alloenduracididine
• guanidines
• synthesis