Modular approaches to lankacidin antibiotics
| Autor: | Lingchao Cai, Yanmin Yao, Ian B. Seiple, Seul Ki Yeon |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular Staphylococcus aureus medicine.drug_class Antibiotics Computational biology Microbial Sensitivity Tests 010402 general chemistry Lankacidins Crystallography X-Ray 01 natural sciences Biochemistry Streptomyces Catalysis Article Micrococcus Polyketide Colloid and Surface Chemistry Models medicine Cancer Crystallography biology Molecular Structure business.industry Chemistry Molecular Stereoisomerism General Chemistry Modular design biology.organism_classification Antimicrobial 0104 chemical sciences Anti-Bacterial Agents Infectious Diseases Chemical Sciences X-Ray Macrolides business Bacillus subtilis |
| Zdroj: | J Am Chem Soc Journal of the American Chemical Society, vol 142, iss 35 |
| Popis: | Lankacidins are a class of polyketide natural products isolated from Streptomyces spp. that show promising antimicrobial activity. Owing to their complex molecular architectures and chemical instability, structural assignment and derivatization of lankacidins are challenging tasks. Herein we describe three fully synthetic approaches to lankacidins that enable access to new structural variability within the class. We use these routes to systematically generate stereochemical derivatives of both cyclic and acyclic lankacidins. Additionally, we access a new series of lankacidins bearing a methyl group at the C4 position, a modification intended to increase chemical stability. In the course of this work, we discovered that the reported structures for two natural products of the lankacidin class were incorrect, and we determine the correct structures of 2,18-seco-lankacidinol B and iso-lankacidinol. We also evaluate the ability of several iso- and seco-lankacidins to inhibit the growth of bacteria and to inhibit translation in vitro. This work grants insight into the rich chemical complexity of this class of antibiotics and provides an avenue for further structural derivatization. |
| Databáze: | OpenAIRE |
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