Chemical modification of peptides containing .gamma.-carboxyglutamic acid

Abstract

At acidic pH the -proton of the -carboxyglutamic acid (Gla) side chain undergoes rapid exchange. We have utilized the reactivity of the resulting enol form to develop a method for the chemical modification of peptide-bound Gla residues. Reaction of Gla peptides with a morpholine-formaldehyde mixture at pH 4.5 yields the Mannich base adduct. Fragmentation of the Mannich base occurs rapidly in 50% aqueous DMF to yield carbon dioxide, morpholine, and the corresponding -methyleneglutamyl residue.

Scalable Total Syntheses of N-Linked Tryptamine Dimers by Direct Indole−Aniline Coupling: Psychotrimine and Kapakahines B and F

“…The copper/zinc-mediated coupling proved to be reliable on a large scale if the iodoalanine 121 was synthesized and used quickly due to slow decomposition. Methyl ester hydrolysis of the alkyne and peptide coupling to H 2 N-Ala-Leu-OBn proceeded with high efficiency to provide tripeptide 116 .…”

Enantiospecific Total Syntheses of Kapakahines B and F

“…7 Tripeptide 4 was prepared on decagram scale by hydrolysis of 6, followed by coupling with H 2 N-Ala-Leu-OBn. 8 The total synthesis of 1 and 2 was completed as shown in Scheme 2. Thus, protected dipeptide 3 is reacted with o-iodoaniline and N-iodosuccinimide in the absence of an acid-scavenger to afford the indole-aniline coupled product 7 in 65% yield as a single diastereomer.…”

“…The preparation of tripeptide 4 , as depicted in Scheme , utilizes Knochel’s method to convert serine-derived 5 to the silyl alkyne 6 . Tripeptide 4 was prepared on decagram scale by hydrolysis of 6 , followed by coupling with H 2 N-Ala-Leu-OBn . The total synthesis of 1 and 2 was completed as shown in Scheme .…”