US 6,632,942 B2 · Asymmetric synthesis of piperazic acid and derivatives thereof

Abstract

This invention provides a concise, asymmetric synthesis of piperazic acid and derivatives thereof, whereby either the (3S)- or (3R)-enantiomeric form may be obtained with high optical purity. (3S)-piperazic acid is derived from D-glutamic acid through an (R)-2,5-dihydroxyvalerate ester intermediate. After the hydroxy groups are converted to suitable leaving groups, such as mesylates, the ester is treated with a bis-protected hydrazine to provide the desired (3S)-piperazic acid derivative. The (3R) enantiomer of piperazic acid may be similarly obtained starting with L-glutamic acid. The method may also be used to obtain piperazic acid derivatives that have moderate optical purity or are racemic. By this method, piperazic acid derivatives may be obtained that are useful as intermediates for pharmacologically active compounds. For example, certain intermediates of this invention are useful for preparing caspase inhibitors, particularly inhibitors of ICE, through additional steps known in the art.

Claims46

Dependent claims

A method for preparing a compound having the formula:

wherein:
R is hydrogen or a carboxyl protecting group;
and
each R1 and R2 are independently selected from hydrogen or an amino protecting group, wherein R1 and R2 may be taken together to form a fused bicyclic or tricyclic amino protecting group;
provided that R1 and R2 are not simultaneously hydrogen;
said process comprising the steps of:
(a) providing a compound of formula II:
wherein —OR4 is a suitable leaving group;
and
(b) treating II with a compound of formula III:
in the presence of a suitable organic solvent and a suitable base to produce I.

8 more elements

Dependencies are inferred from the claim text.

Asymmetric synthesis of piperazic acid and derivatives thereof

Life of this patent

Asymmetric synthesis of piperazic acid and derivatives thereof

Life of this patent

Abstract

Claims46