title: 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.
abstract: 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.
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Yoshinari
authors.initials: Y
authors.lastname: Wakiyama
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Kumura
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Eijiro
authors.initials: E
authors.lastname: Umemura
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Satomi
authors.initials: S
authors.lastname: Masaki
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Ueda
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Hirai
authors.affiliation: Pharmaceutical Research Center, Meiji Seika Pharma Co., Ltd., Yokohama, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Ajito
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D002981:Clindamycin / Q000494:pharmacology; D008034:Lincomycin / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012335:RNA, Ribosomal / Q000235:genetics; D012141:Respiratory Tract Infections / Q000188:drug therapy / Q000382:microbiology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D012335:RNA, Ribosomal; D002981:Clindamycin; D008034:Lincomycin