Epoxycarboxamide compound, azide compound, and amino alcohol compound, and process for preparing alpha-keto amide compound using them
The present invention is to provide manufacturing intermediates which can be led to useful α-ketoamide compounds having protease-inhibiting activity extremely economically and stereoselectively, and to provide epoxycarboxamide compounds, azide compounds and amino alcohol compounds represented by the following formulae: wherein R 1 and R 2 each represents alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group; R 3 represents alkyl group, alkenyl group, aromatic hydrocarbon group, heterocyclic group, R 6 —O— or R 7 —N(R 8 )—; where R 6 represents alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group; R 7 and R 8 each represents hydrogen atom, alkyl group, alkenyl group, aromatic hydrocarbon group or heterocyclic group, and, R 4 and R 5 represent the same groups as R 7 and R 8 , respectively, and R 4 and R 5 optionally form a ring together; and X represents —O— or —N(R 9 )—, where R 9 represents hydrogen atom or alkyl group, and X optionally forms a ring together with R 4 or R 5 , and processes for preparing α-keto amide compound using the same.
1. An epoxycarboxamide compound of the formula (I):
wherein
(A) R 1 is a substituted or unsubstituted, straight, branched or cyclic alkyl group, the substituent for the alkyl group being
a substituted or unsubstituted aromatic hydrocarbon group,
a substituted or unsubstituted heterocyclic group,
a substituted or unsubstituted alkoxy group,
a substituted or unsubstituted alkylthio group,
a substituted or unsubstituted aryloxy group, or
a substituted or unsubstituted arylthio group; and
R 2 is
a substituted, straight, branched or cyclic alkyl group, the substituent for the alkyl group being
a hydroxyl group,
an oxo group,
a halogen atom,
a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms,
a substituted or unsubstituted heterocyclic group,
a nitro group,
a substituted or unsubstituted amino group,
a substituted or unsubstituted sulfonyl group,
a substituted or unsubstituted alkoxy group,
a substituted or unsubstituted alkylthio group,
a substituted or unsubstituted aryloxy group,
a substituted or unsubstituted arylthio group,
an acyl group,
a substituted or unsubstituted alkoxycarbonyl group,
a substituted carbamoyl group,
a substituted sulfonamide group,
a substituted amide group,
a mercapto group, or
a cyano group;
wherein when R 2 is a substituted methyl group, the substituent for the methyl group is
a hydroxyl group,
a halogen atom,
a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms,
a substituted or unsubstituted heterocyclic group,
a substituted or unsubstituted amino group,
a substituted or unsubstituted alkoxy group,
a substituted or unsubstituted alkylthio group,
a substituted or unsubstituted aryloxy group,
a substituted carbamoyl group,
a substituted sulfonamide group,
a substituted amide group, or
a mercapto group;
wherein when R 2 is a substituted, branched 3-methylbutyl group or a substituted branched 2-methylpropyl group, the substituent for the 3-methylbutyl group or 2-methylpropyl group in R 2 is
a hydroxyl group,
an oxo group,
a halogen atom,
a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms,
a substituted or unsubstituted heterocyclic group,
a nitro group,
a substituted or unsubstituted amino group,
a substituted or unsubstituted sulfonyl group,
a substituted or unsubstituted alkoxy group,
a substituted or unsubstituted alkylthio group,
a substituted or unsubstituted aryloxy group,
a substituted or unsubstituted arylthio group,
an acyl group,
a substituted alkoxycarbonyl group,
a substituted carbamoyl group,
a substituted sulfonamide group,
a substituted amide group,
a mercapto group, or
a cyano group; or
(B) R 1 is
an unsubstituted alkyl group selected from the group consisting of:
a methyl group,
an ethyl group,
a n-propyl group,
a 1-methylethyl group,
a cyclopropyl group,
a n-butyl group,
a t-butyl group,
a 2-methylpropyl group,
a 1-methylpropyl group,
a 1,1-dimethylethyl group, and
a cyclobutyl group; or
a substituted alkyl group,
the substituent for the alkyl group being a substituted or unsubstituted heterocyclic group, a substituted or unsubstituted alkoxy group, a substituted or unsubstituted alkylthio group, a substituted or unsubstituted aryloxy group, or a substituted or unsubstituted arylthio group; and
R 2 is an unsubstituted, straight, branched or cyclic alkyl group.
2. The epoxycarboxamide compound according to claim 1 , wherein the compound of formula (I) has the formula:
wherein R 1 and R 2 are as defined in claim 1 .
3. The epoxycarboxamide compound according to claim 1 , wherein the compound of formula (I) has the formula:
wherein R 1 and R 2 are as defined in claim 1 .
4. The epoxycarboxamide compound according to claim 1 , wherein the compound of formula (I) has the formula:
wherein R 1 and R 2 are as defined in claim 1 .
5. The epoxycarboxamide compound according to claim 1 , wherein the compound of formula (I) has the formula:
wherein R 1 and R 2 are as defined in claim 1 .
6. The epoxycarboxamide compound according to claim 1 , wherein R 1 is an unsubstituted alkyl group.
7. An epoxycarboxamide compound of the formula (I):
wherein
(A) R 1 is an n-butyl group; and
R 2 is
a substituted, straight, branched or cyclic alkyl group, the substituent for the alkyl group being
a hydroxyl group,
an oxo group,
a halogen atom,
a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms,
a substituted or unsubstituted heterocyclic group,
a nitro group,
a substituted or unsubstituted amino group,
a substituted or unsubstituted sulfonyl group,
a substituted or unsubstituted alkoxy group,
a substituted or unsubstituted alkylthio group,
a substituted or unsubstituted aryloxy group,
a substituted or unsubstituted arylthio group,
an acyl group,
a substituted or unsubstituted alkoxycarbonyl group,
a substituted carbamoyl group,
a substituted sulfonamide group,
a substituted amide group,
a mercapto group, or
a cyano group; or
(B) R 1 is an n-butyl group; and
R 2 is an unsubstituted, straight, branched or cyclic alkyl group.
8. An epoxycarboxamide compound of the formula (I):
wherein R 1 is a substituted or unsubstituted, straight, branched or cyclic alkyl group, and
the substituent for the alkyl group is
a substituted or unsubstituted aromatic hydrocarbon group,
a substituted or unsubstituted heterocyclic group,
a substituted or unsubstituted alkoxy group,
a substituted or unsubstituted alkylthio group,
a substituted or unsubstituted aryloxy group, or
a substituted or unsubstituted arylthio group; and
R 2 is a substituted or unsubstituted cyclic alkyl group, and
the subsubstituent for the alkyl group is
a hydroxyl group,
an oxo group,
a halogen atom,
a substituted or unsubstituted, straight, branched or cyclic alkenyl group having 2 to 6 carbon atoms,
a substituted or unsubstituted heterocyclic group,
a nitro group,
a substituted or unsubstituted amino group,
a substituted or unsubstituted sulfonyl group,
a substituted or unsubstituted alkoxy group,
a substituted or unsubstituted alkylthio group,
a substituted or unsubstituted aryloxy group,
a substituted or unsubstituted arylthio group,
an acyl group,
a substituted or unsubstituted alkoxycarbonyl group,
a substituted carbamoyl group,
a substituted sulfonamide group,
a substituted amide group,
a mercapto group, or
a cyano group.
9. The epoxycarboxamide compound according to claim 8 , wherein R 2 is a substituted or unsubstituted cyclohexyl group.
10. The epoxycarboxamide compound according to claim 8 , wherein a substituent for the cyclic alkyl group of R 2 is a hydroxyl group.
11. The epoxycarboxamide compound according to claim 10 , wherein R 2 has the formula: