Solid-supported synthesis of cryptand-like macrobicyclic peptides.
A straightforward method for the solid-supported synthesis of cryptand-like bicyclic peptides (1-5) on a backbone amide linker has been described. For the branching, two novel easily available building blocks, viz. N-(4-methoxytrityl)-N-(2-nitrobenzenesulfonyl)-protected N,N-bis(2-aminoethyl)-beta-alanine (6) and N-(9-fluorenylmethoxycarbonyl) protected iminodiacetic acid monoallyl ester (7), have been employed. The key steps of the synthesis are as follows: (i) stepwise coupling of one amino acid and 6 to the secondary amino group of the linker; (ii) removal of the 2-nitrobenzenesulfonyl group and SPPS by the Fmoc chemistry, using 7 as the penultimate and tert-butoxycarbonyl (Boc) protected glycine as the last amino acid; (iii) removal of the 4-methoxytrityl protection and subsequent SPPS by the Fmoc chemistry; (iv) removal of the allyl and Fmoc groups, followed by cyclization; and (v) removal of the Boc and tert-butyl groups, followed by cyclization. Final cleavage from the support and removal of benzyl-derived protecting groups gives the desired bicyclic products.
Department of Chemistry, University of Turku, FIN-20014 Turku, Finland. pasi.virta@utu.fi
Pasi
P
Virta
Harri
H
Lönnberg
D000577:Amides / Q000737:chemistry; D000596:Amino Acids / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid; D020650:Combinatorial Chemistry Techniques; D004988:Ethers, Cyclic / Q000737:chemistry*; D007769:Lactams / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D012545:Schiff Bases / Q000737:chemistry*
D000577:Amides; D000596:Amino Acids; D004988:Ethers, Cyclic; D007769:Lactams; D010456:Peptides, Cyclic; D012545:Schiff Bases; C444241:cryptand