[Back]

U. Jordis, J. Phopase:
"Preparation of modified amino acids, especially N-oxalyl amino acid hydrazides, and their use as building blocks for peptide and amino acid mimetics and analogs";
Patent: WO, No. 2007095980 A1; submitted: 11-24-2006, granted: 08-30-2007.

Abstract

The invention is related to the prepn. of N-oxalyl amino acid hydrazides and their use as building blocks for peptide and amino acid mimetics and analogs, esp. R4R3N-N(R2)-COXN(R1)COCOR5 [X = unsubstituted 5-11 membered heteroarylene, (un)substituted alk(en/yn)ylene, cycloalkylene, 3-20 membered heterocyclylene, excluding 1,6-naphthyridinylenes; R5 = SR10, OR10, NR10R11, provided NR10R11 is not the amide functionality of an amino acid hydrazide, or R5 can form with R2 or R3 a bond or an 8-10 membered heterocyclyl; R10 and R11 = independently H, (un)substituted cycloalkyl, aryl, alk(en/yn)yl, 3-14 membered heterocyclyl or heteroaryl; R3R4 = a double bond to a group R12; R12 = (un)substituted cycloalkyl, alk(en/yn)yl, 3-14 membered heterocyclyl or heteroaryl; R2 = H, R12; preferably R2 = H; R1, R3, R4 = independently H, aryl, R12; optionally at least two of R1-R4 and X can form a (preferably monocyclyl) 3-10 membered ring; with provisos], and their esters, amides, salts, stereoisomers and racemates, by reacting a precursor L1COXNR1L2 with a hydrazine or hydrazine deriv. R4R3N-NR2L3 and an oxalic acid, ester or deriv. L4COCOR5, in any order [L1-L4 = independently arbitrary leaving groups or H, preferably L4 = Cl, OH, an activated ester or an anhydride]. Thus, a 10-step combined liq. and solid phase synthesis from N-(benzyloxycarbonyl)-L-phenylalanine hydrazide via amidation of [(S)-1-[[2-((S)-2-amino-3-phenylpropionyl)hydrazino]carbonyl]ethyl]carbamic acid tert-Bu ester (prepn. given) with Me oxalyl chloride was given for Boc-Phe-Ala-NPheO-OH.

Amino Acids, Peptides, Solid phase synthesis, peptidomimetics