Improved Synthesis of the New Furo[3,2-h]isoquinoline Alkaloids TMC-120B and TMC-120A, and Their Inhibitory Activities against IFN-γ and IL-4 Production

Abstract

In our synthetic route of TMC-120B (2), the synthetic intermediate, methyl [7-(methoxycarbonyl)-3-methyl-8-isoquinolyloxy]acetate (8) was newly synthesized in seven steps along with an improvement of the overall yield.The catalytic hydrogenation of TMC-120B (2) was also improved.Inhibition of interferon-!and interleukin-4 production by TMC-120A (1), TMC-120B (2), and their derivative 4 was evaluated.The results indicated that these compounds are selective inhibitors of Th1 cell function.