Chiral vinylogous amino sulfonic acids (vs-amino acids) were synthesized starting from either L-or D-alpha-amino acids via N-Boc-alpha-amino aldehydes. Wittig-Homer reaction with methyl (or ethyl) diethylphosphoryl methanesulfonate and nBuLi gave the corresponding alpha,beta-unsaturated sulfonates in high yield and complete (E) stereoselectivity. Cleavage of the methyl (ethyl) ester was effected by treatment of the sulfonates with nBu(4)NI in refluxing acetone. Treatment of the nBu(4)N(+) sulfonate salts with SO2Cl2/PPh3/CH2Cl2 gave the corresponding sulfonyl chlorides as stable chromatographable compounds. The synthetic sequence proved successful not only starting from alpha-amino acids carrying unfunctionalized side-chains (Ala, Val, Phe, Leu, Pro), but also with functionalized alpha-amino acids (Ser, Tyr, Gin) 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 alpha-amino acids and vs-amino acids. Proteinogenic alpha-amino acids were incorporated at both the C-terminal and the N-terminal position.

Synthesis of chiral vinylogous sulfonamidopeptides (vs-peptides) / C.M.A. Gennari, C. Longari, S. Ressel, B. Salom, A. Mielgo. - In: EUROPEAN JOURNAL OF ORGANIC CHEMISTRY. - ISSN 1434-193X. - 1998:6(1998), pp. 945-959. [10.1002/(SICI)1099-0690(199806)1998:6<945::AID-EJOC945>3.0.CO;2-3]

Synthesis of chiral vinylogous sulfonamidopeptides (vs-peptides)

C.M.A. Gennari
Primo
;
1998

Abstract

Chiral vinylogous amino sulfonic acids (vs-amino acids) were synthesized starting from either L-or D-alpha-amino acids via N-Boc-alpha-amino aldehydes. Wittig-Homer reaction with methyl (or ethyl) diethylphosphoryl methanesulfonate and nBuLi gave the corresponding alpha,beta-unsaturated sulfonates in high yield and complete (E) stereoselectivity. Cleavage of the methyl (ethyl) ester was effected by treatment of the sulfonates with nBu(4)NI in refluxing acetone. Treatment of the nBu(4)N(+) sulfonate salts with SO2Cl2/PPh3/CH2Cl2 gave the corresponding sulfonyl chlorides as stable chromatographable compounds. The synthetic sequence proved successful not only starting from alpha-amino acids carrying unfunctionalized side-chains (Ala, Val, Phe, Leu, Pro), but also with functionalized alpha-amino acids (Ser, Tyr, Gin) 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 alpha-amino acids and vs-amino acids. Proteinogenic alpha-amino acids were incorporated at both the C-terminal and the N-terminal position.
Iterative synthesis; N-Boc-α-amino aldehydes; Pseudopeptides; Sulfonamides; Vinylogous sulfonamidopeptides
Settore CHIM/06 - Chimica Organica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/177134
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