180675-60-9Relevant academic research and scientific papers
Synthesis of chiral vinylogous sulfonamidopeptides (vs-peptides)
Gennari, Cesare,Longari, Chiara,Ressel, Stefano,Salom, Barbara,Mielgo, Antonia
, p. 945 - 959 (2007/10/03)
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 nBuLi 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 nBu4NI in refluxing acetone. Treatment of the nBu4N+ sulfonate salts with SO2Cl2/PPh3/CH2Cl2 gave the corresponding sulfonyl chlorides as stable chromatographable 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 vstripeptides 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.
