Solid Phase Synthesis of Peptidyl Thioacids Employing a 9-Fluorenylmethyl Thioester-Based Linker in Conjunction with Boc Chemistry

摘要

A method for the synthesis of peptidyl thioacids is described based on the use of the N-[9-(thiomethyl)-9H-fluoren-2-yl]succinamic acid and cross-linked aminomethyl polystyrene resin. The method employs standard Boc chemistry SPPS techniques in conjunction with 9-fluorenylmethyloxycarbonyl protection of side chain alcohols and amines, and 9-fluorenylmethyl protection of side chains acids and thiols. Cleavage from the resin is accomplished with piperidine, which also serves to remove the side chain protection and avoids the HF conditions usually associated with the resin cleavage stage of Boc chemistry SPPS. The so-obtained thioacids are converted to simple thioesters in high yield by standard alkylation according to well-established methods.