(Cyanomethylene) phosphoranes as carbonyl 1,1-dipole synthons for use in constructing combinatorial libraries
AssigneeYale University
InventorsHarry H. Wasserman, Wen-Bin Ho
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Abstract
The invention is directed to systematic synthetic and testing strategies for .alpha.-keto acids, esters and amides. The method of synthesis comprises (A) reacting (cyanomethylene)triphenylphosphorane with a carbonyl compound selected from carboxylic acids (RCOOH) and acyl chlorides (RCOCl) to make a cyano keto phosphorane, (B) oxidizing said phosphorane and (C) reacting the oxidized product with a nucleophile (NuH) to make the product .alpha.-keto acid, ester or amide. Systematic synthesis and testing are achieved by a modular approach in which arrays of molecules are generated by variation of R and Nu.
Claims6
A method for making a ketone containing compound comprising the steps of
- (A) reacting a (cyanomethylene)triphenylphosphorane with a carbonyl containing compound selected from the group consisting of carboxylic acid of formula RCOOH, acid anhydride derived therefrom or acyl chloride of formula RCOCl, wherein R is a structural diversity element selected from the group consisting from alkyl, cycloalkyl, substituted and unsubstituted aryl, heteroaryl, peptidyl, heteroatom-substituted alkyl and cycloalkyl, to make the corresponding cyano keto phosphorane;
- (B) oxidizing said cyano keto phosphorane to make an .alpha.-ketoacyl cyanide;
- and
- (C) reacting said .alpha.-ketoacyl cyanide with a nucleophile of formula NuH wherein NuH is a structural diversity element selected from the group consisting of amine, amino acid, peptidyl residue, water, H.sub.2 S, alcohol and thiol, to form a ketone-containing compound.
Dependencies are inferred from the claim text.