Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• 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. Keywords: antibiotic; argyrin

• relationship for the natural argyrins A–H revealed argyrin B as most potent derivative (2, IC50 0.08 µg/mL). In 1996, two cyclic peptides with a similar sequence but a proposed regioisomer of the methoxytryptophan were reported as antibiotics A21459A and B [7][10]. Later, it was shown that A21459A and B are

• identical to argyrin A and B, respectively, and their structure was revised with respect to the position of the methoxy substituent [6]. Argyrin A demonstrated a high efficacy against a panel of P. aeruginosa multidrug resistant (MDR) strains and the argyrins were shown to bind to elongation factor G (EF-G

Studies on the synthesis of peptides containing dehydrovaline and dehydroisoleucine based on copper-mediated enamide formation

• Franziska Gille and
• Andreas Kirschning

Beilstein J. Org. Chem. 2016, 12, 564–570, doi:10.3762/bjoc.12.55

• microbial sources. Typical examples are myxovalargin (1), argyrin (2) and nisin (3, Scheme 1). Dehydroamino acids and peptides are characterized by the presence of an olefinic double bond conjugated with the carboxyl or peptidic carbonyl group. Besides being α,β-unsaturated acids or amides, respectively

• typically this is achieved by elimination when a leaving group occupies the β-position [2]. Especially peptides containing dehydroalanine as found in argyrin (2) can be prepared from a precursor that contains a selenide substituent in the β-position [3]. Peptides that bear the doubly branched dehydroamino

• ), argyrin A (2) and nisin (3) (in myxovalargin dehydroamino acids and neighboring amino acids are numbered). The Buchwald cross-coupling reaction in the preparation of peptides containing dehydroamino acids 4. Syntheses of vinyl iodides 10 and 11. Preparation of vinyl iodides 24–29 (Cbz = benzyloxycarbonyl