482598-87-8Relevant academic research and scientific papers
Synthesis of a new turn mimic bearing a β-lactam moiety
Maier, Thomas C.,Frey, Wolfgang U.,Podlech, Joachim
, p. 2686 - 2689 (2007/10/03)
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-prohne 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]jethoxy}-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.
