title: Improved synthesis of capuramycin and its analogues.
abstract: Capuramycin and its congeners are considered to be important lead molecules for the development of a new drug for multidrug-resistant (MDR) Mycobacterium tuberculosis infections. Extensive structure-activity relationship studies of capuramycin to improve the efficacy have been limited because of difficulties in selectively chemically modifying the desired position(s) of the natural product with biologically interesting functional groups. We have developed efficient syntheses of capuramycin and its analogues by using new protecting groups, derived from the chiral (chloro-4-methoxyphenyl)(chlorophenyl)methanols, for the uridine ureido nitrogen and primary alcohol. The chiral nonracemic (2,6-dichloro-4-methoxyphenyl)(2,4-dichlorophenyl)methanol derivative is a useful reagent to resolve rac-3-amino-1,3-dihydro-5-phenyl-2H-1,4-benzodiazepin-2-one, the (S)-configuration isomer of which plays a significant role in improving the mycobactericidal activity of capuramycin.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee Health Science Center, 881 Madison, Memphis, TN 38163-0001 (USA), Fax: (+1) 901-448-6940.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Shajila
authors.initials: S
authors.lastname: Siricilla
authors.forename: Bilal A
authors.initials: BA
authors.lastname: Aleiwi
authors.forename: Michio
authors.initials: M
authors.lastname: Kurosu
mesh_terms: D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D015394:Molecular Structure; D009161:Mycobacterium / Q000737:chemistry* / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000617:Aminoglycosides; D000995:Antitubercular Agents; C049983:capuramycin
keywords: capuramycin; drug design; mycobacterium tuberculosis; peptidoglycan biosynthesis; protecting groups; total synthesis