Xu Fan, Smith Myles W
Department of Biochemistry, UT Southwestern Medical Center 5323 Harry Hines Blvd Dallas Texas 75390 USA
Chem Sci. 2021 Sep 23;12(41):13756-13763. doi: 10.1039/d1sc03533a. eCollection 2021 Oct 27.
The indoxyl unit is a common structural motif in alkaloid natural products and bioactive compounds. Here, we report a general method that transforms readily available 2-substituted indoles into 2,2-disubstituted indoxyls nucleophile coupling with a 2-alkoxyindoxyl intermediate and showcase its utility in short total syntheses of the alkaloids brevianamide A (7 steps) and trigonoliimine C (6 steps). The developed method is operationally simple and demonstrates broad scope in terms of nucleophile identity and indole substitution, tolerating 2-alkyl substituents and free indole N-H groups, elements beyond the scope of most prior approaches. Spirocyclic indoxyl products are also accessible intramolecular nucleophilic trapping.
吲哚酚单元是生物碱天然产物和生物活性化合物中常见的结构基序。在此，我们报道了一种通用方法，该方法通过与2-烷氧基吲哚酚中间体进行亲核偶联，将易于获得的2-取代吲哚转化为2,2-二取代吲哚酚，并展示了其在生物碱短叶酰胺A（7步）和三角叶藜碱C（6步）的全合成中的应用。所开发的方法操作简单，在亲核试剂特性和吲哚取代方面具有广泛的适用范围，能够耐受2-烷基取代基和游离的吲哚N-H基团，这是大多数先前方法所无法涵盖的。螺环吲哚酚产物也可通过分子内亲核捕获得到。
