Evolution of a Strategy for the Unified Synthesis of Enteropeptin Sactipeptides
Shuvendu Saha, Yiwei Zhang, Yesen Cheng, Chi P. Ting
TL;DR
The paper describes the development of a new method to synthesize sactipeptides, a type of antibiotic peptide, using a more efficient and unified approach.
Contribution
The novel contribution is a modular synthesis strategy that enables unified synthesis of enteropeptin sactipeptides through early formation of the thiomorpholine ring.
Findings
Late-stage hydrothiolation of an 8-mer peptide was unsuccessful.
An annulation reaction formed the thiomorpholine ring but with low yield.
A divergent synthesis strategy enabled unified synthesis of enteropeptin sactipeptides.
Abstract
Sactipeptides are a class of natural product peptides with remarkable antibiotic properties that are defined by the presence of thioaminoketals in their structure. Recently, we reported the first total synthesis of a sactipeptide in our synthesis of enteropeptin A. The key to our synthesis involved the use of a dithiophosphoric acid catalyzed Markovnikov hydrothiolation of dehydroamino acids. With this reaction, thioaminoketals found in sactipeptides can be prepared directly from a dehydroamino acid and a cysteine residue. This article summarizes our initial approach toward enteropeptin synthesis and the evolution of our strategy that ultimately enabled the synthesis of these peptide natural products. Our first strategy involved late-stage Markovnikov hydrothiolation of an 8-mer peptide containing a dehydroamino acid and a cysteine residue that was unsuccessful. The second strategy…
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Taxonomy
TopicsSulfur-Based Synthesis Techniques · Chemical Synthesis and Analysis · Click Chemistry and Applications