Atom-economical synthesis of the N(10)-C(17) fragment of cyclotheonamides via a novel Passerini reaction-deprotection-acyl migration strategy.
[reaction: see text]. A novel variant of the atom-economical Passerini reaction between suitably protected argininal, dipeptide isonitrile, and proline components afforded adduct 13. Orthogonal N-deprotection of 13 led, via a smooth O- to N-acyl migration, to 14, which constitutes the N(10)-C(17) fragment of the cyclotheonamide family of serine protease inhibitors. Each reaction in this three-step protocol proceeds in good yield and under very mild conditions.
Owens
T D
TD
Department of Medicinal Chemistry, Corvas International, Inc., 3030 Science Park Road, San Diego, California 92121, USA.
Semple
J E
JE
D000215:Acylation; D000818:Animals; D000991:Antithrombins / Q000138:chemical synthesis; D010446:Peptide Fragments / Q000138:chemical synthesis; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D011161:Porifera / Q000737:chemistry; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis*
D000991:Antithrombins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D015842:Serine Proteinase Inhibitors; C096691:cyclotheonamide C; C096692:cyclotheonamide D; C096693:cyclotheonamide E; C112727:cyclotheonamide E2; C112728:cyclotheonamide E3; C081986:cyclotheonamide A