Efficient Synthesis of Enantiopure Pyrrolizidinone Amino Acid
Enantiopure (3S,5R,8S)-3-[N-(Boc)amino]-1-azabicyclo[3.3.0]octan-2-one 8-carboxylic acid (1) was synthesized in nine steps and 16% overall yield from aspartate β-aldehyde 7. Carbene-catalyzed acyloin condensation of 7, followed by acetylation and samarium iodide reduction, gave linear precursor (2S,...
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Published in | Journal of organic chemistry Vol. 68; no. 18; pp. 6988 - 6996 |
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Main Authors | , |
Format | Journal Article |
Language | English |
Published |
WASHINGTON
American Chemical Society
05.09.2003
Amer Chemical Soc |
Subjects | |
Online Access | Get full text |
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Summary: | Enantiopure (3S,5R,8S)-3-[N-(Boc)amino]-1-azabicyclo[3.3.0]octan-2-one 8-carboxylic acid (1) was synthesized in nine steps and 16% overall yield from aspartate β-aldehyde 7. Carbene-catalyzed acyloin condensation of 7, followed by acetylation and samarium iodide reduction, gave linear precursor (2S,7S)-α,ω-diamino-4-oxosuberate 11, which was converted to N-(Boc)aminopyrrolizidin-2-one carboxylic acid 1 by a reductive amination/lactam cyclization sequence. X-ray analysis of (3S,5R,8S)-methyl N-(Boc)aminopyrrolizidin-2-one carboxylate 21 showed that its internal backbone dihedral angles (ψ = −149°, φ = −49°) were in good agreement with the ideal values for a type II‘ β-turn. Proton NMR experiments on N ‘-methyl-N-(Boc)aminopyrrolizidin-2-one carboxamide 23 demonstrated significantly different NH chemical displacements and temperature coefficients suggestive of solvent shielded and exposed hydrogens indicative of a turn conformation. Because pyrrolizidinone amino acids can serve as conformationally rigid dipeptide surrogates, this synthesis should facilitate their application in the exploration of conformation−activity relationships of various biologically active peptides. |
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Bibliography: | istex:037B337E8E1846A41378DA5547D6E53D416B2E88 ark:/67375/TPS-8H89MJLH-N ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3263 1520-6904 |
DOI: | 10.1021/jo034739d |