Total synthesis of thaxtomin A analogues and their intermediates
View Patent ↗Improved synthetic methods for the production of thaxtomin analogs, particularly thaxtomin A, and intermediates therefore such as substituted tryptophans and in particular, 4-nitro-L-tryptophan, and substituted phenyl acrylic acids are disclosed. Bioassays show that the synthetic thaxtomin A is not significantly different from the natural one in herbicidal activity.
1. A method for the synthesis of a thaxtomin or analog thereof having the structure (I)
wherein R1 is NO 2 and R2 is selected from a lower alkyl, hydroxyl, halogen, fluoromethyl, difluoromethyl, trifluoromethyl, nitro, amine, methoxy, fluoromethoxy, difluoromethoxy, and trifloromethoxy, comprising:
(a) reacting a tryptophan amide analog having the structure
with substituted phenyl acrylic acid having the structure
wherein R is selected from a lower alkyl, hydroxyl, halogen, fluoromethyl, difluoromethyl, trifluoromethyl, nitro, amine, methoxy, fluoromethoxy, difluoromethoxy, and trifloromethoxy, or its keto tautomer to obtain a compound having the structure (A2)
wherein R1 is NO 2 and R2 is selected from a lower alkyl, hydroxyl, halogen, fluoromethyl, difluoromethyl, trifluoromethyl, nitro, amine, methoxy, fluoromethoxy, difluoromethoxy, and trifloromethoxy; and
(b) subjecting the compound having the structure (A2) to a cyclization agent to obtain the structure (I).
2. The method according to claim 1 , wherein said thaxtomin analogue is thaxtomin A having the structure
3. The method according to claim 1 , wherein said substituted phenylacrylic acid has the structure
wherein R is OH or its keto tautomer.
4. The method according to claim 3 , wherein said substituted phenylacrylic acid has the structure
5. The method according to claim 1 , wherein the cyclization is by means of an organic base.
6. The method according to claim 5 wherein the organic base is potassium hydroxide.
7. The method according to claim 5 , wherein the organic base is a chiral Lewis base.
8. The method according to claim 5 wherein the organic base is selected from the group consisting of substituted or unsubstituted pyridine, amine, imidazole, benzimidazole, histidine, and phosphazene.