Synthesis of UDP-Glucose:
Disclosed is a novel enantiomeric synthesis ceramide-like inhibitors of UDP-glucose: N-acylsphingosine glucosyltransferase. Also disclosed are novel intermediates formed during the synthesis.
1. A method of preparing a sphingosine-like compound represented by the following structural formula:
said method comprising the stop of reacting a cyclic starting material with HNR 2 R 3 ,said starting material represented by the following structural formula:
thereby forming an intermediate represented by the following structural formula:
and hydrolyzing the amino acetal group of the intermediate, thereby forming an acyclic compound represented by the following structural formula:
reacting the acyclic compound with an amide reducing agent, thereby forming an amine compound represented by the following structural formula:
debenzylating the —NHCH(—CH 2 OH)R 5 group of the amine compound, thereby forming a sphingosine-like compound represented by the following structural formula:
wherein:
R 1 is a substituted or unsubstituted aromatic group;
R 2 and R 3 are independently —H, a substituted or unsubstituted aliphatic group or, taken together with the nitrogen atom to which they art bonded, are a substituted or unsubstituted non-aromatic heterocyclie ring; and
R 5 is a substituted or unsubstituted aromatic group.
2. The method of claim 1 wherein the amine compound is debenzylated by hydrogenation.
3. The method of claim 2 wherein the amine compound is debenzylated by hydrogenation under a hydrogen atmosphere with a catalytic amount of a hydrogenation catalyst.