Department of Chemistry, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Nat Chem. 2018 Jan;10(1):85-90. doi: 10.1038/nchem.2863. Epub 2017 Sep 18.
The selective (and controllable) modification of complex molecules with disparate functional groups (for example, natural products) is a long-standing challenge that has been addressed using catalysts tuned to perform singular transformations (for example, C-H hydroxylation). A method whereby reactions with diverse functional groups within a single natural product are feasible depending on which catalyst or reagent is chosen would widen the possible structures one could obtain. Fluoroarylborane catalysts can heterolytically split Si-H bonds to yield an oxophilic silylium (RSi) equivalent along with a reducing (H) equivalent. Together, these reactive intermediates enable the reduction of multiple functional groups. Exogenous phosphine Lewis bases further modify the catalyst speciation and attenuate aggressive silylium ions for the selective modification of complex natural products. Manipulation of the catalyst, silane reagent and the reaction conditions provides experimental control over which site is modified (and how). Applying this catalytic method to complex bioactive compounds (natural products or drugs) provides a powerful tool for studying structure-activity relationships.
用催化剂来选择性（可控）地修饰具有不同官能团（例如天然产物）的复杂分子，这是一个长期存在的挑战，目前已经有方法可以解决这个问题，该方法可以通过调节催化剂来执行单一的转化（例如，C-H 羟化）。如果有一种方法可以根据所选择的催化剂或试剂来实现单一天然产物中具有不同官能团的反应，那么就可以拓宽可能获得的结构范围。氟芳基硼烷催化剂可以异裂 Si-H 键，生成亲电性的硅鎓（RSi）等价物以及还原（H）等价物。这些反应性中间体共同作用可以还原多种官能团。外加的膦路易斯碱进一步修饰催化剂的种类，以及减弱硅鎓离子的活性，从而实现对复杂天然产物的选择性修饰。通过对催化剂、硅烷试剂和反应条件的操控，可以实现对修饰位点（以及修饰方式）的实验控制。将这种催化方法应用于复杂的生物活性化合物（天然产物或药物），为研究结构-活性关系提供了一种强大的工具。
