Lactones
The present disclosure relates to novel lactones such as dihydropyrrole-fused furanones, a novel palladium-catalyzed carbonylation method to make the novel lactones, and method of using the novel lactones as anti-fungal and/or anti-bacteria agents.
1. A compound of formula (I)
or any salt thereof, wherein
R 1 is H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, hydroxyl, C1-C6 straight or branched alkoxyl, —C(X)—R 10 , —C(X)—OR 11 , —SO 2 R 12 , —C(X)NR 13 R 14 , or a nitrogen-protecting group, wherein the alkyl, aryl or heteroaryl is optionally substituted with one or more —NO 2 , halogen, CF 3 , or phenyl;
R 2 , R 3 , R 4 , and R 5 are independently H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, hydroxyl, halogen, or C1-C6 straight or branched alkoxyl, wherein the alkyl, aryl or heteroaryl is optionally substituted with one or more —NO 2 , halogen, CF 3 , or phenyl;
R 6 , R 7 are independently H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, C1-C6 straight or branched alkoxyl, wherein R 6 , R 7 may form a C3-C10 carbon ring or heterocyclic ring comprising N, O, or S, and when the heterocyclic formed by R 6 and R 7 has N, the N is optionally attached to C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, —C(X)—R 10 , —C(X)—OR 11 , —SO 2 R 12 , —C(X)NR 13 R 14 , or a nitrogen-protecting group;
R 10 -R 14 are independently H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, wherein the alkyl, aryl, or heteroaryl is optionally substituted with one or more C1-C4 straight or branched alkyl, —NO 2 , halogen, or CF 3 ; and
X is O or S.
2. The compound of claim 1 , wherein the compound is made by a method comprises reacting a compound of formula A with carbon monoxide, a palladium catalyst, a ligand, and an oxidant in a solvent to provide the compound of formula I:
3. The compound of claim 1 , wherein the compound is selected from the group consisting of:
4. The compound of claim 1 , wherein the compound is used as an anti-bacteria or anti-fungal agent.
5. A method of preparing the compound of formula (I) of claim 1 , wherein the method comprises reacting a compound of formula A with carbon monoxide, a palladium catalyst, a ligand, and an oxidant in a solvent to provide the compound of formula I:
R 1 is H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, hydroxyl, C1-C6 straight or branched alkoxyl, —C(X)—R 10 , —C(X)—OR 11 , —SO 2 R 12 , —C(X)NR 13 R 14 , or a nitrogen-protecting group, wherein the alkyl, aryl or heteroaryl is optionally substituted with one or more —NO 2 , halogen, CF 3 , or phenyl;
R 2 , R 3 , R 4 , and R 5 are independently H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, hydroxyl, halogen, or C1-C6 straight or branched alkoxyl, wherein the alkyl, aryl or heteroaryl is optionally substituted with one or more —NO 2 , halogen, CF 3 , or phenyl;
R 6 , R 7 are independently H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, C1-C6 straight or branched alkoxyl, wherein R 6 , R 7 may form a C3-C10 carbon ring or heterocyclic ring comprising N, O, or S, and when the heterocyclic formed by R 6 and R 7 has N, the N is optionally attached to C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, —C(X)—R 10 , —C(X)—OR 11 , —SO 2 R 12 , —C(X)NR 13 R 14 , or a nitrogen-protecting group;
R 10 -R 14 are independently H, C1-C8 straight or branched alkyl, C3-C8 cycloalkyl, C6-C10 aryl, C4-C10 heteroaryl, wherein the alkyl, aryl, or heteroaryl is optionally substituted with one or more C1-C4 straight or branched alkyl, —NO 3 , halogen, or CF 3 ; and
X is O or S.