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 an acylated ceramide compound represented by the following structural formula:
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 are bonded, are a substituted or unsubstituted non-aromatic heterocyclic ring; and
R 7 is a substituted or unsubstituted aliphatic group;
said method comprising the steps of:
a) reacting an acyclic compound represented by the following structural formula:
with an amide reducing agent, thereby forming an amine compound represented by the following structural formula:
b) 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:
c) acylating the primary amine group of the sphingosine-like compound, thereby forming the acylated ceramide compound.
2. A method of preparing an acylated ceramide compound represented by the following structural formula:
R 1 is para-hydroxyphenyl or
R 7 is a C7-C10 alkyl group;
said method comprising the steps of:
a) reacting an acyclic compound represented by the following structural formula:
with an amide reducing agent, thereby forming an amine compound represented by the following structural formula:
b) debenzylating the —NHCH(—CH 2 OH)(phenyl) group of the amine compound, thereby forming a sphingosine-like compound represented by the following structural formula:
c) acylating the primary amine group of the sphingosine-like compound, thereby forming the acylated ceramide compound.
3. The method of claim 2 , wherein the ceramide compound is represented by the following structural formula:
and the sphingosine-like compound is represented by the following structural formula
4. The method of claim 3 , wherein the sphingosine-like compound is acylated with CH 3 (CH 2 ) 6 COX, wherein X is a leaving group, thereby forming the ceramide compound.
5. The method of claim 4 , wherein X is —Cl or N-hydroxysuccinimidyl.