Synthesis and structure–activity relationships of novel lincomycin derivatives. Part 2. Synthesis of 7(S)-7-deoxy-7-(4-morpholinocarbonylphenylthio)lincomycin and its 3-dimensional analysis with rRNA
| Autor: | Takashi Watanabe, Ko Kumura, Kazutaka Ueda, Keiichi Ajito, Eijiro Umemura, Yoko Hirai, Satomi Masaki, Mikio Yamamoto, Yoshinari Wakiyama |
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| Rok vydání: | 2015 |
| Předmět: |
0301 basic medicine
Antiparasitic medicine.drug_class Stereochemistry 030106 microbiology Biology 01 natural sciences Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound Biosynthesis Drug Discovery medicine Respiratory Tract Infections Pharmacology chemistry.chemical_classification Bacteria 010405 organic chemistry Clindamycin Aryl Bacterial Infections Glycopeptide Anti-Bacterial Agents Lincomycin 0104 chemical sciences chemistry RNA Ribosomal Thiol SN2 reaction Mitsunobu reaction medicine.drug |
| Zdroj: | The Journal of Antibiotics. 69:428-439 |
| ISSN: | 1881-1469 0021-8820 |
| DOI: | 10.1038/ja.2015.125 |
| Popis: | Lincomycin derivatives, which possess a hetero ring at the C-7 position via sulfur atom, were synthesized by three types of reactions: (1) Mitsunobu reaction of 2,3,4-tris-O-(trimethylsiliyl)lincomycin (1) with the corresponding thiol, (2) SN2 reaction of 7-O-methanesulfonyl-2,3,4-tris-O-(trimethylsiliyl)lincomycin (2) with the corresponding thiol and (3) Pd-catalyzed cross-coupling reaction of 7-deoxy-7-epi-7-mercaptolincomycin (35) with the corresponding aryl halides. As a result, compound 28 had potent antibacterial activities against major pathogens, which caused respiratory infections, even compared with clindamycin. On the other hand, compound 38 showed most potent activities against a variety of Streptococcus pneumoniae with erm gene. |
| Databáze: | OpenAIRE |
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