Caudill Laboratories, Department of Chemistry , University of North Carolina at Chapel Hill , Chapel Hill , North Carolina 27599-3290 , United States.
Chemical and Analytical Development - Novartis Pharma AG , Basel , Switzerland.
Org Lett. 2019 May 3;21(9):3451-3455. doi: 10.1021/acs.orglett.9b01245. Epub 2019 Apr 17.
Site selective amide reductions of the cyclic undecapeptide, cyclosporine A, have been developed using the combination of a heteroleptic borane catalyst and a silane reductant. Tertiary silane MeEtSiH provides two unique cyclosporine A derivatives, one of which can be readily diversified in subsequent reactions. The secondary silane EtSiH enables divergent reactivity that uses a free hydroxyl group to direct the reduction. The transient O-silyl hemiaminal intermediate of this reduction can additionally be trapped by reducing to the amine or by reductive cyanation.
已开发出一种使用杂化硼烷催化剂和硅烷还原剂的组合，实现了环十一肽，环孢菌素 A 的选择性酰胺还原。叔硅烷 MeEtSiH 提供了两种独特的环孢菌素 A 衍生物，其中一种可以在后续反应中轻松多样化。仲硅烷 EtSiH 使反应具有不同的反应性，利用游离的羟基来导向还原。这种还原的瞬态 O-硅基半亚胺中间体还可以通过还原为胺或通过还原氰化来捕获。
