Ryosuke Ushijima

An efficient synthesis of the side chain intermediate of BO-2502A, a new 1β-methyl carbapenem, via diastereoselective lactamization as a key step

Abstract The BO-2502A side chain intermediate 3 was prepared via the diastereoselective lactamization of the in situ prepared amino diacid anhydride 14 as a key step. The diastereoselectivity of this step was found to be 53:1 (96% de).

DIASTEREOSELECTIVE SYNTHESIS OF THE KEY INTERMEDIATE OF THE BO-2727 SIDE CHAIN

Abstract The key intermediate of the BO-2727 side chain 3 was prepared diastereoselectively by two alternative methods: via the aldol reaction of (2S,4R)-N-Boc- tert -butyldimethylsilyloxyprolinal 5 with in-situ -generated ketene acetal 9 in the presence of TiCl 4 (95% de) and via the catalytic hydrogenation of β-keto amide 6i using (S)-BINAP-Ru as a catalyst (98% de).

An efficient asymmetric synthesis of the mercaptopyrrolidine side chain of an important β-methyl carbapenem antibiotic

Abstract An efficient asymmetric synthesis of the mercaptopyrrolidine side chain 2 1s described. The β-ketoester 4 is hydrogenated diastereoselectively to give the (R)-β-hydroxyester 5. The remaining functional groups are installed via a thiol Mitsunobu reaction and a reduction of a secondary amide to produce 2 in 34% overall yield from BOC-L-trans-4-hydroxyproline methylester 3 (Scheme 1).

Novel dithiocarbamate carbapenems1 with anti-MRSA activity

Abstract A new series of carbapenems, in which disubstituted-aminothiocarbonylthio moiety, directly attached to the C-2 position, were prepared and evaluated for their antibacterial potency. These analogs showed potent activity against high-level MRSA. Among them, 9e and 9i were found to exhibit good in vivo efficacy comparable to that of vancomycin, for mouse septicemia model with high-level MRSA.