摘要：

The first total synthesis of madindolines A and B, potent selective inhibitors of interleukin 6 (IL-6), has been achieved by stereoselective aldol reaction, ring-closing metathesis, reductive amination, followed by an asymmetric oxidative ring closure of indole, and resulted in determination of their absolute stereochemistries. We have further developed a more efficient second-generation synthesis, which is suitable for gram-scale preparation of these compounds, by stereoselective acylation of ester 34, followed by an intramolecular acylation of ester 32 with allylsilane (19% yield over 9 steps). Synthetic [ H]-madindoline A bound to gp-130, selectively. Furthermore, synthetic madindoline A markedly inhibited osteoclastogenesis in vitro and bone resorption in ovariectomized mice in vivo.

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