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β‐Lactam‐Containing Cyclopeptide Analogs
Author(s) -
Maier Thomas C.,
Podlech Joachim
Publication year - 2004
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.200400295
Subject(s) - chemistry , moiety , peptidomimetic , saponification , stereochemistry , yield (engineering) , peptide , nuclear magnetic resonance spectroscopy , cleavage (geology) , lactam , amino acid , cyclic peptide , organic chemistry , biochemistry , materials science , geotechnical engineering , fracture (geology) , engineering , metallurgy
Cyclic peptide analogs containing a β‐lactam moiety were prepared. Reacting Fmoc‐protected amino acid‐derived diazo ketones 1 , 2 with benzylidene‐protected amino esters 3 , 4 in a photochemically induced Staudinger‐type reaction, trans ‐substituted β‐lactams 5a/b and 6a/b were formed in 35−70% yield ( dr 60:40−70:30). N ‐Terminal chain elongation to the respective acyclic precursors 14 , 17a/b and 19a/b was achieved using conventional peptide synthesis (i.e. the pentafluorophenyl ester protocol). After saponification, activation as pentafluorophenyl esters and subsequent cleavage of the N ‐terminal Boc‐protecting group, the pre‐strained (3 R ,4 S )‐configured isomers could be cyclized without the need for high dilution or prolonged reaction times. Contrary to this, the (3 S ,4 R )‐configured isomers did not cyclize but gave polymeric material. The conformational stability of the cyclic peptidomimetics 16 , 20 , and 21 which were obtained in high yield, was elucidated by means of NMR spectroscopy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)