Coste Alexis, Kim Justin, Adams Timothy C, Movassaghi Mohammad
Massachusetts Institute of Technology, Department of Chemistry, 77 Massachusetts Avenue 18-292, Cambridge, MA 02139-4307, USA.
Chem Sci. 2013 Aug;4(8):3191-3197. doi: 10.1039/C3SC51150B.
The concise and efficient total synthesis of (+)-bionectins A and C is described. Our approach to these natural products features a new and scalable method for -β-hydroxytryptophan amino acid synthesis, an intramolecular Friedel-Crafts reaction of a silyl-tethered indole, and a new mercaptan reagent for epipolythiodiketopiperazine (ETP) synthesis that can be unravelled under very mild conditions. In evaluating the impact of C12-hydroxylation, we have identified a unique need for an intramolecular variant of our Friedel-Crafts indolylation chemistry. Several key discoveries including the first example of permanganate-mediated stereoinvertive hydroxylation of the α-stereocenters of diketopiperazines as well as the first example of a direct triketopiperazine synthesis from a parent -dipeptide are discussed. Finally, the synthesis of (+)-bionectin A and its unambiguous structural assignment through X-ray analysis provides motivation for the reevaluation of its original characterization data and assignment.
本文描述了（+）-生物连接素A和C的简洁高效全合成。我们合成这些天然产物的方法具有一种新的、可扩展的β-羟基色氨酸氨基酸合成方法、一种硅烷基连接吲哚的分子内傅克反应，以及一种用于表聚硫二酮哌嗪（ETP）合成的新型硫醇试剂，该试剂可在非常温和的条件下解开。在评估C12-羟基化的影响时，我们发现对我们的傅克吲哚化化学的分子内变体有独特需求。讨论了几个关键发现，包括二酮哌嗪α-立体中心的高锰酸盐介导的立体反转羟基化的首个实例，以及从母体二肽直接合成三酮哌嗪的首个实例。最后，（+）-生物连接素A的合成及其通过X射线分析的明确结构归属为重新评估其原始表征数据和归属提供了动力。
