118235-03-3Relevant academic research and scientific papers
Total synthesis of the didemnins; IV. Synthesis of the peptolide ring and construction of the side chain
Schmidt,Kroner,Griesser
, p. 294 - 300 (2007/10/02)
A total synthesis of didemnins A, B, and C (1-3) which enables these highly cytotoxic cyclopeptides to be prepared in decigram amounts is described. The β-keto acid unit (hydroxyisovaleryl)propionic acid derivative (Hip, 6) was prepared by acylation of dibenzyl methylmalonate and subsequent cleavage of the benzyl groups by the action of boron trichloride. The free β-keto acid 6 was activated by the DCC method and allowed to react with the leucine ester 7 to furnish the amide 8. Activation, deprotection, and ring closure of the linear peptide 19 by means of the pentafluorophenyl ester method in a two-phase system gave rise to the didemnin ring skeleton in 75% yield within a few minutes. The respective side chains were then attached to the didemnin ring easily and in high yields by activation of Z-(R)-N-methylleucine as its 3-cyano-2-pyridylthiol ester followed by reaction with Z-lactylproline chloride and Z-lactic acid chloride.
Amino Acids and Peptides; 67. Easy Preparation and Use of Benzyloxycarbonyl Derivatives of Amino Acid Chlorides and α-Hydroxycarboxylic Acid Chlorides
Schmidt, Ulrich,Kroner, Matthias,Beutler, Ulrich
, p. 475 - 477 (2007/10/02)
N-Benzyloxycarbonyl amino acid chlorides and α-benzyloxycarbonyloxy carboxylic acid chlorides are readily available by treating the corresponding carboxylic acids with 1-chloro-N,N,2-trimethyl-1-propen-1-amine.They can be immediately reacted with O-, N- and C-nucleophiles to afford peptides, ketones and esters.
