Stereoselective synthesis of highly functionalized thiopeptide thiazole fragments from uronic acid/cysteine condensation products: access to the core dipeptide of the thiazomycins and nocathiacins

• Published in: Tetrahedron Vol. 68; no. 35; pp. 7166 - 7178
• Main Authors: Enck, Sebastian, Tremmel, Peter, Eckhardt, Sonja, Marsch, Michael, Geyer, Armin
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 02.09.2012; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; Carbohydrates with 4, 5, 6, ... C atoms, dissacharides and oligosaccharides; Carbohydrates. Nucleosides and nucleotides; Chemistry; Chemistry, Organic; Cysteine; Exact sciences and technology; General aspects; Heterocyclic compounds; Heterocyclic compounds with n hetero atom and also o and/or s, se, te hetero atoms; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Medical sciences; Organic chemistry; Pharmacology. Drug treatments; Physical Sciences; Polyols; Preparations and properties; Science & Technology; Sugar amino acids; Thiazoles; Thiazolidine lactams; Thiopeptides; Cysteine; Sugar amino acids; Thiazolidine lactams; Polyols; Thiopeptides; Thiazoles; KEY BUILDING-BLOCKS; ORGANIC-CHEMISTRY; ANTIBIOTICS; THIOSTREPTON; PEPTIDE; TUBULYSIN; BIOSYNTHETIC GENE-CLUSTER; MANGANESE-DIOXIDE OXIDATION; CONSTRUCTION; AMYCOLATOPSIS-FASTIDIOSA; Nitrogen heterocycle; Cyclic peptides; Thiazole derivatives; Epimer; Lactam; Oxygen heterocycle; Stereoselectivity; Ester; Functionalization; Oxidation; Polyol; Chemical synthesis; Protection; Sulfur nitrogen heterocycle; Condensation reaction; Lactone; Oside; Natural compound; Sulfur containing aminoacid; Antibiotic; Sulfur peptide; Multigram scale; Absolute configuration; Uronic acid; Dipeptides; Indole derivatives; Thiazolidine derivatives
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.06.022

We present the stereoselective synthesis of various highly functionalized thiazole dipeptides that are found in thiopeptide antibiotics like thiazomycins and nocathiacins. The condensation of an uronic acid with l-cysteine methyl ester delivers along two different protocols the stereopure thiazolidine lactones or lactams on the multigram scale, respectively. Oxidation of the thiazolidine moiety to the thiazole and tailoring of the sugar chains yield the thiazole dipeptide as present in the core motif of the thiopeptide antibiotics, as well as its epimer and a homolog. The modular assembly of the potent natural products and their analogs relies on the synthetic accessibility of adequately protected building blocks of tailored absolute stereochemistry. [Display omitted]