Concise Total Synthesis of (+)-Bionectins A and C

• Published in: Chemical science (Cambridge) Vol. 4; no. 8; pp. 3191 - 3197
• Main Authors: Coste, Alexis, Kim, Justin, Adams, Timothy C, Movassaghi, Mohammad
• Format: Journal Article
• Language: English
• Published: England 01.08.2013
• Subjects: Amino acids; Friedel-Crafts reaction; Hydroxylation; Mercaptans; Parents; Synthesis; Synthesis (chemistry); X-rays
• ISSN: 2041-6520; 2041-6539
• 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.