Studies on Peptides. CLV. Evaluation of Trimethylsilyl Bromide as a Hard-Acid Deprotecting Reagent in Peptide Synthesis

• Published in: Chemical & pharmaceutical bulletin Vol. 35; no. 9; pp. 3880 - 3883
• Main Authors: FUJII, NOBUTAKA, OTAKA, AKIRA, SUGIYAMA, NAOKI, HATANO, MIKA, YAJIMA, HARUAKI
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 1987; Maruzen; Japan Science and Technology Agency
• Subjects: Amino Acids; Asp-side reaction; Chemical Phenomena; Chemistry; Chromatography, High Pressure Liquid; Exact sciences and technology; hard acid deprotecting reagent; human gastrin-releasing peptide; Indicators and Reagents; Met sulfoxide; Organic chemistry; peptide synthesis; Peptides; Peptides - chemical synthesis; Preparations and properties; soft nucleophile; thioanisole; trifluoromethanesulfonic acid; trimethylsilyl bromide; Trimethylsilyl Compounds; trimethylsilyl trifluoromethanesulfonate; trymethylsilyl bromide; Gastrine releasing peptide; Oligopeptides; Aminoacid; Silicon Organic compounds; Deprotection; Hormone releasing factor; Peptidic synthesis
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.35.3880

Trimethylsilyl bromide (TMSBr) in trifluoroacetic acid (TFA) was found to have the ability to cleave benzyl-type protecting groups, i.e., benzyloxycarbonyl (Z), benzyl (O-Bzl) and p-methoxybenzyl (S-MBzl). The reaction was best accelerated by addition of thioanisole, compared with other soft nucleophiles so far examined. The rate of the cleavage reaction with TMSBr/TFA was judged to be somewhat slower than that with trimethylsilyl trifluoromethanesulfonate/TFA. However, TMSBr/TFA reduced Met (O) efficiently and gave almost no side reaction of Asp (succinimide formation). This deprotecting procedure was applied to the synthesis of human gastrin-releasing peptide.