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Synthesis of a New Turn Mimic Bearing a β‐Lactam Moiety
Author(s) -
Maier Thomas C.,
Frey Wolfgang U.,
Podlech Joachim
Publication year - 2002
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 - 10.1002/1099-0690(200208)2002:16<2686::aid-ejoc2686>3.0.co;2-1
Subject(s) - chemistry , moiety , turn (biochemistry) , stereochemistry , peptidomimetic , lactam , yield (engineering) , amide , glycine , amino acid , peptide , organic chemistry , biochemistry , materials science , metallurgy
A new turn mimic derived from PLG (prolyl‐leucyl‐glycine amide) containing a β‐lactam in the turn area has been prepared. The β‐lactam moiety was furnished by treating an Fmoc‐protected leucine‐derived diazo ketone 2 with a benzylidene‐protected glycine ester in a photochemically induced Staudinger‐type reaction. The trans ‐substituted β‐lactams 3a / b are formed in 70% yield ( dr 70:30). Separation of the isomers, deprotection and attachment of Fmoc‐proline using the pentafluorphenyl ester activation protocol yielded the protected peptidomimetic 4 in 93% yield. Deprotection and amidation resulted in formation of the target substrate 1 in 82% yield but with a low purity. Better results were obtained using Nsc ({2‐[(4‐nitrophenyl)sulfonyl]ethoxy}carbonyl) as protection for proline. It could be cleaved yielding a spectroscopically pure product 1 whose structure was elucidated by X‐ray crystallographic analysis. It shows an open turn conformation, i.e., the turn is not stabilized by a hydrogen bond between the termini of the turn region. (© Wiley‐VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)