Cephalosporins to carbapenems: 1-oxygenated carbapenems and carbapenams.
The photo "Wolff" rearrangement of readily available 2-diazoceph-3-em oxides (1) directly affords carbapen-2-ems, allowing a facile entry into a ring system previously accessible only by total synthesis, lengthly semisynthesis or fermentation. The chirality of the cephalosporin is accurately translated into the corresponding carbapenem. The resulting 1-oxocarbapenems (2) were selectively transformed through reduction into 1-oxygenated carbapenems and carbapenams (3 and 4, respectively). On microbiological screening, a carbapenem (3c) was found to possess a broad spectrum of activity. An interesting antibacterial profile was discovered for a carbapenam (26).
Rosati
R L
RL
Pfizer Central Research, Groton, Connecticut 06340.
Kapili
L V
LV
Morrissey
P
P
Retsema
J A
JA
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D015780:Carbapenems / Q000138:chemical synthesis* / Q000494:pharmacology; D055598:Chemical Phenomena; D002621:Chemistry; D004926:Escherichia coli / Q000187:drug effects; D007711:Klebsiella pneumoniae / Q000187:drug effects; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010777:Photochemistry; D011511:Proteus / Q000187:drug effects; D013211:Staphylococcus aureus / Q000187:drug effects; D013845:Thienamycins
D000900:Anti-Bacterial Agents; D015780:Carbapenems; D013845:Thienamycins