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US 2006/0235226 A1Published application
Synthesis of diketopiperazines
AssigneeNereus Pharmaceuticals, Inc.
InventorYoshio Hayashi
Life of this patent
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Abstract
Disclosed herein are methods for synthesizing diketopiperazines with enantiomeric excess by inducing cyclization of an α-keto acid with an acid catalyst.
Claims12
A method of preparing a compound of formula I:
- comprising reacting an acid catalyst with a compound of formula II in such a manner so as to produce the compound of formula I with an enantiomeric excess greater than about 50%:
- wherein:
- R1, R2, and R3 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, alkoxy, acyl, arylalkyl, heteroarylalkyl, alkyloxycarbonyloxy, ester, arylalkoxy, alkoxy, or alkylthio;
- mono-substituted, poly-substituted or unsubstituted variants of the following residues:
- acyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, cycloalkoxy, aryl, heteroaryl, heterocycloalkyl, carbonyl, carbonylacyl, amino, aminocarbonyl, amide, aminocarbonyloxy, nitro, azido, phenyl, hydroxyl, arylthio, oxysulfonyl, carboxy, and cyano;
- R4 and R5 are separately selected from the group consisting of hydrogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 heteroalkyl, C2-6 aminoalkyl, C2-6 haloalkyl, C1-6 alkoxycarbonyl, aryl-C1-6-alkyl, or C2-6 hydroxyalkyl;
- mono-substituted, poly-substituted or unsubstituted variants of the following residues:
- C3-8 cycloalkyl, —C(O)—C5-6 aryl substituted with C1-3 alkyl or halo, C5-6 aryl, C5-6 heteroaryl, C5-6 cycloalkyl, and C5-6 heterocycloalkyl;
- any bond represented by a dashed and solid line represents a bond selected from the group consisting of a single bond and a double bond;
- and
- any carbon-carbon double bond has a configuration selected from the group consisting of cis and trans.
13 more elements
A method of preparing a compound of formula II:
- comprising performing the following reaction:
- wherein:
- R1, R2, and R3 are separately selected from the group consisting of hydrogen;
- halogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-C24 alkyl, C2-C24 alkenyl, C2-C24 alkynyl, alkoxy, acyl, arylalkyl, heteroarylalkyl, alkyloxycarbonyloxy, ester, arylalkoxy, alkoxy, or alkylthio;
- mono-substituted, poly-substituted or unsubstituted variants of the following residues:
- acyloxy, aryloxycarbonyloxy, cycloalkyl, cycloalkenyl, cycloalkoxy, aryl, heteroaryl, heterocycloalkyl, carbonyl, carbonylacyl, amino, aminocarbonyl, amide, aminocarbonyloxy, nitro, azido, phenyl, hydroxyl, arylthio, oxysulfonyl, carboxy, and cyano;
- and
- R4 and R5 are separately selected from the group consisting of hydrogen;
- mono-substituted, poly-substituted or unsubstituted, straight or branched chain variants of the following residues:
- C1-6 alkyl, C2-6 alkenyl, C2-6 alkynyl, C2-6 heteroalkyl, C2-6 aminoalkyl, C2-6 haloalkyl, C1-6 alkoxycarbonyl, aryl-C1-6-alkyl, or C2-6 hydroxyalkyl;
- mono-substituted, poly-substituted or unsubstituted variants of the following residues:
- C3-8 cycloalkyl, —C(O)—C5-6 aryl substituted with C1-3 alkyl or halo, C5-6 aryl, C5-6 heteroaryl, C5-6 cycloalkyl, and C5-6 heterocycloalkyl.
11 more elements
Dependencies are inferred from the claim text.