Chisato Sato

Novel efficient synthesis of 1-azabicyclo[1.1.0]butane and its application to the synthesis of 1-(1,3-thiazolin-2-yl)azetidine-3-thiol useful for the pendant moiety of an oral 1β-methylcarbapenem antibiotic L-084

1-Azabicyclo[1.1.0]butane 2 was successfully synthesized by treatment of 2,3-dibromopropylamine hydrobromide 4 with organolithium compounds and was readily converted to 1-(1,3-thiazolin-2-yl)azetidine-3-thiol hydrochloride 1 and versatile azetidine derivatives 9 and 10.

Syntheses and Pharmacokinetic Studies of Prodrug Esters for the Development of Oral Carbapenem, L-084

We discovered an orally active carbapenem, L-084, through pharmacokinetic studies on various prodrug esters of (1R,5S,6S)-6-[(R)-1-hydroxyethyl]-1-methyl-2-[1-(1,3-thiazolin-2-yl)azetidin-3-yl]thio-1-carbapen-2-em-3-carboxylic acid (LJC11,036). L-084 showed a strong antimicrobial activity against Gram-positive and Gram-negative bacteria and exhibited the highest intestinal absorption among synthesized prodrugs of LJC11,036.

A biogenetically patterned total synthesis of prostaglandin E1

Abstract Methyl 11-tert-butyldimethylsilyloxyeicosa-8(Z), 12(E), 14(E)-trienoate was stereoselectively cyclized by treatment with Hg(OCOCF3)2 to give a properly functionalized PG skeleton, which was converted to PGE1 in good over all yield.