Depsipeptide synthesis.
Naturally occurring cyclic depsipeptides, peptides that contain one or more ester bonds in addition to the amide bonds, have emerged as an important source of pharmacologically active compounds or promising lead structures for the development of novel synthetically derived drugs. This class of natural products has been found in many organisms, such as fungi, bacteria, and marine organisms. It is very well known that cyclic depsipeptides and their derivatives exhibit a diverse spectrum of biological activities, including insecticidal, antiviral, antimicrobial, antitumor, tumor-promotive, anti-inflammatory, and immunosuppressive actions. However, they have shown the greatest therapeutic potential as anticancer and particularly antimicrobial agents. Difficulties associated with isolation and purification of larger quantities of this class of natural products and, particularly, unlimited access to their synthetic analogs significantly hampered cyclic depsipeptides exploitation as lead compounds for development of new drugs. As an alternative, total solution or solid-phase peptide synthesis of these important natural products and combinatorial chemistry approaches can be employed to elucidate structure-activity relationships and to find new potent compounds of this class. In this chapter, methods for formation of depsipeptide ester bonds, hydroxyl group protection, and solid-phase reaction monitoring are described.
Stawikowski
Maciej
M
Department of Chemistry & Biochemistry, Florida Atlantic University, Boca Raton, USA.
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D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D017576:Daptomycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D047630:Depsipeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004951:Esterification; D006900:Hydroxylation; D007202:Indicators and Reagents; D008967:Molecular Biology / Q000379:methods; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D052616:Solid Phase Extraction
D000900:Anti-Bacterial Agents; D047630:Depsipeptides; D007202:Indicators and Reagents; D010456:Peptides, Cyclic; C041438:ramoplanin; D017576:Daptomycin