Design and Enantioselective Synthesis of β‑Vinyl Tryptamine Building Blocks for Construction of Privileged Chiral Indole Scaffolds

The highly efficient and stereo-specific synthesis of the enantioenriched versatile building blocksnamely, β-vinyltryptaminesby rhodium-catalyzed allylic substitutions of vinylaziridines and indoles is presented. Besides indoles, pyrroles can also serve as competent carbon nucleophiles in the current reaction, which is different from the previous works. To demonstrate the synthetic utility of our method, up to 11 natural product and pharmaceutically relevant chiral indole scaffolds were synthesized in highly efficient reaction sequences. Notably, asymmetric formal synthesis of a potent constrained analogue of MS-245 and a nNOS and 5-HT1B/1D receptor inhibitor are also reported.

本文报道了通过铑催化乙烯基氮丙啶与吲哚（indole）的烯丙基取代反应，实现对映体富集的多功能构筑单元——即β-乙烯基色胺——的高效立体专一性合成。除吲哚外，吡咯亦可作为本反应中有效的碳亲核试剂，这与既往研究成果有所不同。为验证本方法的合成实用性，我们通过高效反应序列合成了多达11种与天然产物及药物相关的手性吲哚骨架。值得注意的是，本文还报道了强效MS-245受限类似物，以及一种神经型一氧化氮合酶（nNOS）与5-羟色胺1B/1D（5-HT1B/1D）受体抑制剂的不对称形式合成。