1211774-34-3Relevant academic research and scientific papers
Function-oriented synthesis of simplified caprazamycins: Discovery of oxazolidine-containing uridine derivatives as antibacterial agents against drug-resistant bacteria
Ii, Kensuke,Ichikawa, Satoshi,Al-Dabbagh, Bayan,Bouhss, Ahmed,Matsuda, Akira
scheme or table, p. 3793 - 3813 (2010/07/16)
The rational simplification of the caprazamycin (CPZ) class of nucleoside natural products was carried out to address their molecular complexity. First, analogues 6-8, where the diazepanone ring of the CPZ was removed and a lipophilic side chain was attached to either the C-7′ or N 6′ atom, were used to investigate the conformation-activity relationship. On the basis of this relationship, we designed the oxazolidine-containing uridine derivatives 18-21 by restricting the conformation of 6-8. As a result, the tBu ester derivatives 20 were found to be the most active against a range of bacterial strains containing VRE with a potency similar to that of the parent CPZs. This study provides a novel strategy for the development of a new type of antibacterial agent effective against drug-resistant bacteria.
Total synthesis of (-)-muraymycin D2 and its epimer
Tanino, Tetsuya,Ichikawa, Satoshi,Shiro, Motoo,Matsuda, Akira
experimental part, p. 1366 - 1377 (2010/05/02)
Chemical Equetion Presentation Full details of the first total synthesis of (-)-muraymycin (MRY) D2 and its epimer, the antibacterial nucleoside natural product, are described. Key strategic elements of the approach include the preparation of the urea dipeptide moiety found in the muraymycins containing an L-epi-capreomycidine via a nitrene C-H insertion of the sulfamate 10 and the fully protected muraymycin skeleton at a late stage by an Ugi four-component reaction. Thus, the nitrene C-H insertion of the sulfamate 10 with 10 mol % of Rh2(esp)2 catalyst gave the cyclic sulfamates 11a and 11b in 47% yield (11a:11b = 1:2.0). Construction of the cyclic guanidine skeleton was effected through the HgBr2-promoted cyclization of 42 followed by desulfonylation upon acetolysis of the oxathiazinane ring to give 43 in good yield. The amine obtained by selective removal of the Cbz group of the alcohol 44 was reacted with MeSC(=O)-L-Val-O-t-Bu (38) to provide 45, which was oxidized to the carboxylic acid 46. Reaction of 46, isonitrile 51, isovaleraldehyde, and 2,4-dimethoxybenzylamine furnished the desired Ugi products, the final deprotection of which successfully afforded (-)-MRY D2 and epi-MRY D2 (53) after HPLC separation of the diastereomers. This approach would afford ready access to a range of analogues simply by altering each component.
