Timothy W. Strohmeyer

Preparation of novel tricyclic diazo carbapenems: Application of inverse electron demand Diels-Alder reactions of 3,6-bis(methylthio)-1,2,4,5-tetrazine

Abstract The syntheses of novel tricyclic diazo carbapenem precursor 17 , and the deprotected carbapenems 2 and 3 are described. The construction of the tricyclic carbapenem was accomplished by an intramolecular nucleophilic substitution of the diazine sulfone 16 which was obtained from an inverse electron demand Diels-Alder reaction of the alkynyl azetidinone 13 with 3,6-bis(methylthio)-1,2,4,5-tetrazine (4) .

Synthesis and structure-activity relationships of novel THF 1β-methylcarbapenems II

Abstract A series of twelve highly active aminomethyl-THF 1β-methylcarbapenems 3a-1 were synthesized. Of these, carbapenems 3a-f demonstrated a spectrum of antimicrobial activity comparable to those of imipenem and meropenem with the exception of only moderate anti-pseudomonal activity. Most importantly, they demonstrated moderate intrinsic oral activity against an E. coli infection in mice.

An intramolecular addition-elimination strategy for the synthesis of carbapenems

Abstract The synthesis of 2-[(4-fluorophenylsulfonyl)methyl] carbapenem carboxylate 20 is described. The key step is a base mediated addition-elimination ring closure of a iodovinyl sulfone 12.

Synthesis and structure-activity relationships of some novel oxetane carbapenems

Six disubstituted oxetane carbapenems were synthesized and their antibacterial profile compared with the lead amino methyl THF carbapenem as well as imipenem. The oxetane carbapenems had comparable or less activity against the Gram(−) bacteria and had reduced activity against Gram(+) bacteria in comparison with imipenem and the THF carbapenem CL 191, 121, but were highly stable to hydrolysis by hog kidney dehydropeptidase (DHP).

Mono and bis double ester prodrugs of novel aminomethyl-THF 1β-methylcarbapenems

Mono and bis double ester prodrugs of aminomethyl THF 1β-methylcarbapenems 1 were synthesized. Mono double ester derivatives (2, 4 and 7) did not demonstrate significantly improved oral activity due to the presence of the charged species. However, bis double ester derivatives (3 and 5) demonstrated enhanced oral activity.

Suppression of Ethyl Migration in the Synthesis of 2,5-Anhydro-1-Amino-1,4-Dideoxy-3-Thio-D-Threo-Pentitol Hydrochloride, A Key Intermediate for Oral the 1β-Methylcarbapenems

Abstract A reproducible synthesis of 2,5-anhydro-1-amino-1,4-dideoxy-3-thio-D-threo-pentitol hydrochloride (2b) via the Staudinger reaction with triethyl phosphite was developed. An unexpected ethyl migration from an oxygen to the nitrogen of iminophosphorane 7 was observed.