Synthesis of Combinatorial Libraries of Vinylogous Sulfonamidopeptides (vs-Peptides)

✍ Scribed by Cesare Gennari; Chiara Longari; Stefano Ressel; Barbara Salom; Umberto Piarulli; Simona Ceccarelli; Antonia Mielgo

• Publisher: John Wiley and Sons
• Year: 1998
• Tongue: English
• Weight: 409 KB
• Volume: 1998
• Category: Article
• ISSN: 1434-193X
• DOI: 10.1002/(sici)1099-0690(199811)1998:11<2437::aid-ejoc2437>3.0.co;2-8

✦ Synopsis

Chiral vinylogous sulfonamidopeptides (vs-peptides) were nitrogen atom so as to reduce the acidity of the monomers and of the oligomers and increase their in vivo bioavailability. synthesized on TentaGel resin employing (S)-and (R)-N-Bocvinylogous sulfonyl chlorides 2a-i as building blocks. This synthetic methodology was employed to increase the diversity in a library of di-N-alkylated vs-dipeptides 26. The Glycine and two different photocleavable molecules were used as linkers, and the corresponding cleavage conditions electron-withdrawing capability of the sulfonamido group pointed to the use of vinylogous sulfonamidopeptides as were optimized. According to preliminary studies in solution and on solid phase, three libraries were synthesized with the Michael acceptors. The sodium enolate of dimethyl malonate was used as nucleophile to obtain N-Boc-γ-lactams 35 in "split-mix synthesis" method. Taking advantage of the acidic character of the sulfonamides (RSO 2 -NHR: pK a = 10-11), moderate yields and good diastereoselectivity. mild conditions were developed to alkylate the sulfonamide