There have been numerous reports of polycyclic compounds containing 2,3-disubstituted tetrahydroisoquinolonic acids utilizing the Castagnoli–Cushman reaction or CCR, which have shown to hold tremendous potential in drug discovery and development, as antimalarial agents, kinase (CDK8) inhibitors, GPR40 antagonists, topoisomerase I inhibitors, apoptosis inducers, and antidiabetics. However, no such data has been released, and no further progress has been announced for polycyclic 3-unsubstituted tetrahydroisoquinolonic acids, which sparked our interest in this scaffold. The CCR is somewhat limited by the lack of structurally diverse anhydrides and herein we report a general method into these anhydrides utilizing the Stille reaction. The anhydride for the CCR was prepared by formation of the methyl ester 3 of the commercially available 1,4-dihydroxy-2-napthoic acid 2 followed by selective benzylation 4 and triflation 5. A Stille reaction was used to prepare the diester 6 which was converted to the anhydride 8 under standard conditions. Reaction of the anhydride 8 with 1,3,5-triphenyl-1,3,5-triazinane 9 was accomplished under mild reaction conditions to give 3,4-dihydro-2-N-phenyl-4-carboxy-9-benzyloxybenzo[1,2-f] isoquinoline-1-one, 1.

Facile approach to polycyclic 3-unsubstituted tetrahydroisoquinolonic acid

2019 Spring National Meeting

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