Solid-phase synthesis of peptidyl thioacids employing a 9-fluorenylmethyl thioester-based linker in conjunction with Boc chemistry.
A method for the synthesis of peptidyl thioacids is described on the basis of 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-chain 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.
Crich
David
D
Centre de Recherche de Gif-sur-Yvette, Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, avenue de la Terrasse, 91198 Gif-sur-Yvette, France. dcrich@icsn.cnrs-gif.fr
Sana
Kasinath
K
D005449:Fluorenes / Q000737:chemistry*; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011137:Polystyrenes / Q000737:chemistry; D012117:Resins, Synthetic / Q000737:chemistry; D013237:Stereoisomerism; D013386:Succinates / Q000737:chemistry*; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry
D005449:Fluorenes; C545378:N-(9-(thiomethyl)-9H-fluoren-2-yl)succinamic acid; D010455:Peptides; D011137:Polystyrenes; D012117:Resins, Synthetic; D013386:Succinates; D013438:Sulfhydryl Compounds