105318-41-0Relevant academic research and scientific papers
Synthesis and structure-activity relationships of a novel oral carbapenem, CS-834
Miyauchi, Masao,Endo, Rokuro,Hisaoka, Masafumi,Yasuda, Hiroshi,Kawamoto, Isao
, p. 429 - 439 (1997)
We have studied an ester prodrug of a carbapenem to develop a potent orally active β-lactam antibiotic. A variety of 1β-methylcarbapenem derivatives have been synthesized. We have found that some derivatives having an amide group in the C-2 side chain show potent and well balanced antibacterial activities as well as high stability against dehydropeptidase-I. Oral absorption of derivatives has been optimized by modifying the C-3 ester promoiety. Pivaloyloxymethyl (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[(R)-5-oxopyrrolidin-3-ylthio]-1 -carbapen-2-em-3-carboxylate, CS-834, has been selected as the most promising compound for further evaluation.
Efficient method for the deprotection of tert-butyldimethylsilyl ethers with TiCl4-Lewis base complexes: Application to the synthesis of 1β-methylcarbapenems
Iida, Akira,Okazaki, Hiroki,Misaki, Tomonori,Sunagawa, Makoto,Sasaki, Akira,Tanabe, Yoo
, p. 5380 - 5383 (2007/10/03)
TiCl4-Lewis base (AcOEt, CH3NO2) complexes smoothly deprotected tert-butyldimethylsilyl (TBDMS) ethers. The reaction velocity with these complexes, which seemed less reactive due to the influence of Lewis bases, was considerably greater than that with TiCl4 alone. Selective desilylations between aliphatic and aromatic TBDMS ethers (1 and 5), between 1 and benzyl, allyl, tosyl, methoxyphenyl, and chloroacetyl ethers (13, 14, 15, 16, and 17), and between TBDMS and TBDPS ethers (18 and 19) were successfully performed. Desilylation of TBDMS-aldol, acyloin, and β-lactam analogues 9-12 proceeded smoothly due to anchimeric assistance by the neighboring carbonyl groups. The present method was successfully applied to the practical synthesis of 1β-methylcarbapenems 20a′-f′.
