{Reference Type}: Journal Article
{Title}: Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis.
{Author}: Siebert DCB;Sommer R;Pogorevc D;Hoffmann M;Wenzel SC;Müller R;Titz A;
{Journal}: Beilstein J Org Chem
{Volume}: 15
{Issue}: 0
{Year}: 2019
{Factor}: 2.544
{DOI}: 10.3762/bjoc.15.286
{Abstract}: The argyrins are secondary metabolites from myxobacteria with antibiotic activity against Pseudomonas aeruginosa. Studying their structure-activity relationship is hampered by the complexity of the chemical total synthesis. Mutasynthesis is a promising approach where simpler and fully synthetic intermediates of the natural product's biosynthesis can be biotechnologically incorporated. Here, we report the synthesis of a series of tripeptide thioesters as mutasynthons containing the native sequence with a dehydroalanine (Dha) Michael acceptor attached to a sarcosine (Sar) and derivatives. Chemical synthesis of the native sequence ᴅ-Ala-Dha-Sar thioester required revision of the sequential peptide synthesis into a convergent strategy where the thioester with sarcosine was formed before coupling to the Dha-containing dipeptide.