Diastereoselective synthesis of UDP-glucose: N-acylsphingosine glucosyltransferase inhibitors
AssigneeGenzyme Corporation
InventorBradford H. Hirth
Life of this patent
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Abstract
Disclosed is a method of preparing a composition comprising a compound represented Structural Formula (I): 1 The method comprises the step of reacting an aldehyde compound R10CHO with an isonitrile compound represented by Structural Formula (II): 2
Claims36
A method of preparing a composition comprising a compound represented Structural Formula (I):
- 11
- wherein:
- R10 is a substituted or unsubstituted aromatic group, provided that when R20 and R30 are both —H, then R10 is not 3-pyridyl, phenyl or 4-nitrophenyl;
- and
- R20 and R30 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;
- said method comprising the step of reacting an aldehyde compound R10CHO with an isonitrile compound represented by Structural Formula (II):
- 12
- said method being carried out in the absence of a chiral inducing agent.
A method of preparing a product composition comprising a compound represented by Structural Formula (IV):
- 19
- wherein:
- R10 is a substituted or unsubstituted aromatic group;
- and
- R20 and R30 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;
- said method comprising the step of reacting a starting composition with an amide reducing agent, thereby forming the product composition, wherein the starting composition comprises a compound represented by Structural Formula (III):
- 20
A method of preparing a composition comprising a ceramide-like compound represented by the following structural formula:
- 21
- wherein R7 is a C8-C18 alkyl group;
- said method comprising the steps of:
- a) reacting an aldehyde compound represented by the following structural formula:
- 22
- with an isonitrile compound represented by the following structural formula:
- 23
- thereby forming a composition comprising a heterocyclic compound represented by the following structural formula:
- 24
- b) hydrolyzing the oxazoline group in the heterocyclic compound formed in step a), thereby forming a composition comprising an amide compound represented by the following structural formula:
- 25
- c) reacting the amide compound formed in step b) with lithium aluminum hydride, thereby forming a composition comprising a cyclic amine compound represented by the following structural formula:
- 26
- d) and acylating the primary amine group in the cyclic amine compound formed in step c) with R7COX, wherein is X is —Cl or an N-hdyroxysuccinimdyl group and R7 is a C8-C18 straight chained alkyl group, thereby forming the composition comprising the ceramide-like compound.
A compound represented by Structural Formula (VI):
- 27
- the enantiomer of the compound, a racemic mixture of the compound and enantiomer, and salts thereof, wherein R11 is a substituted or unsubstituted phenyl group.
A compound represented by the following structural formula:
- 28
- the enantiomer of the compound, a racemic mixture of the compound and enantiomer, and salts thereof.
A compound represented by Structural Formula (VII):
- 29
- the enantiomer of the compound, a racemic mixture of the compound and enantiomer, and salts thereof, wherein R12 is a phenyl group substituted with —OCH2CH2O—, halo, OH, —O(lower alkyl), lower alkyl thiol, —O(phenyl), —OCH2-(phenyl), lower alkyl, amino, lower alkyl amino and lower dialkyl amino.
A compound represented by the following structural formula:
- 30
- the enantiomer of the compound, a racemic mixture of the compound and enantiomer, and salts thereof.
Dependencies are inferred from the claim text.