Premium
Synthesis of Chiral Vinylogous Sulfonamidopeptides (vs‐Peptides)
Author(s) -
Gennari Cesare,
Longari Chiara,
Ressel Stefano,
Salom Barbara,
Mielgo Antonia
Publication year - 1998
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/(sici)1099-0690(199806)1998:6<945::aid-ejoc945>3.0.co;2-3
Subject(s) - chemistry , amino acid , tripeptide , sulfonyl , side chain , amine gas treating , residue (chemistry) , acetone , organic chemistry , stereochemistry , biochemistry , alkyl , polymer
Chiral vinylogous amino sulfonic acids (vs‐amino acids) were synthesized starting from either L‐ or D‐α‐amino acids via N ‐Boc–α‐amino aldehydes. Wittig‐Horner reaction with methyl (or ethyl) diethylphosphoryl methanesulfonate and n BuLi gave the corresponding α,β‐unsaturated sulfonates in high yield and complete ( E ) stereoselectivity. Cleavage of the methyl (ethyl) ester was effected by treatment of the sulfonates with n Bu 4 NI in refluxing acetone. Treatment of the n Bu 4 N + sulfonate salts with SO 2 Cl 2 ‐PPh 3 ‐CH 2 Cl 2 gave the corresponding sulfonyl chlorides as stable chromato‐graphable compounds. The synthetic sequence proved successful not only starting from α‐amino acids carrying unfunctionalized side‐chains (Ala, Val, Phe, Leu, Pro), but also with functionalized α‐amino acids (Ser, Tyr, Gln) provided that the side chains were suitably protected. The sulfonyl chlorides were coupled with the amine salts to give vs‐dipeptides. Amine hydrochlorides were prepared from N ‐Boc derivatives by treatment with HCl in methanol or ethyl acetate. The process was further iterated to give vs‐tripeptides and vs‐tetrapeptides. The above procedure was also used to synthesize “mixed” peptides, which incorporate both proteinogenic α‐amino acids and vs‐amino acids. Proteinogenic α‐amino acids were incorporated at both the C‐terminal and the N‐terminal position.