Combinatorial Solid-Phase Synthesis of Structurally Complex Thiazolylhydantoines

Abstract

A nine-step (!) solid-phase synthesis and subsequent cleavage with cyclization from the polymeric support were the keys to preparing high-quality molecular libraries of thiazolylhydantoines 1 from modified amino acid building blocks. Each step in the synthesis is different. Because the final cyclization cleaves only molecules that have been successfully constructed, the products obtained are pure. R , R =alkyl; R =aryl, arylO; R =allyl.

Solid-Phase Synthesis of Guanidinium Derivatives from Thiourea and Isothiourea Functionalities

“…The attachment of thiourea groups to a solid phase is used as a precursor of guanidinium groups, as well as peptidomimetics,60 a quencher,61 thiazolylhydantoines,62 and a precursor to 2‐aminothiazole rings 63. The thiourea moiety is converted into guanidinium functionalities in the presence of different coupling reagents: N , N ‐diisopropylcarbodiimide (DIC), mercury( II ) chloride (HgCl 2 ), mercury( II ) oxide (HgO), 2‐chloro‐1‐methylpyridinium iodide (Mukaiyama’s reagent), 1‐(3‐dimethylaminopropyl)‐3‐ethylcarbodiimide hydrochloride (EDC), 2,4‐dinitrofluorobenzene (Sanger’s reagent), and triphenylphosphane dichloride.…”

Design, Synthesis, and Bioactivation of O-Glycosylated Prodrugs of the Natural Nitric Oxide Precursor Nω-Hydroxy-l-arginine

“…For a series of ethyl ester prodrugs (i.e., 3 , 5 , 6 , 8 ), protected l -ornithine 12 was prepared in two steps from commercially available 10 . First, 10 was treated with phthalic anhydride in tetrachloroethylene and then esterified under Steglich conditions with 4-DMAP, EtOH, and EDCI. , The Alloc group could then be introduced by removing the phthalimide with hydrazine and directly reacting the intermediate ornithine ethyl ester with freshly prepared allyloxycarbonyl isothiocyanate (AllocNCS, 13 ) , to furnish thiourea 14b in moderate yield (40%). Attempts to isolate the intermediate failed largely due to rapid cyclization to a δ-lactam.…”

Synthesis of N-urethane protected amino alkyl (S-methyl)-isothiouronium compounds and carbodiimide tethered peptidomimetics: an application for guanidino and substituted guanidino peptidomimetics synthesis

“…Monosubstituted thiourea derivatives can be accessed through the reaction of primary amines with thiocyanates such as KSCN, NH 4 SCN 14 or coupling with benzoyl isothiocyanate followed by deprotection of benzoyl group. 15 Stadlwieser et al, 16 reported the synthesis of resin bound amino ester derived thioureas, wherein amino acid ester was treated with allyloxycarbonyl (Alloc)-isothiocyanate followed by the removal of Alloc group.…”