Synthesis and structure-activity relationships of quaternary ammonium cephalosporins with 3-pyrazolylpyridinium derivatives.

Cephalosporins with 3-pyazolylpyridinium at C-3 position, which is supposed to exhibit synergic activity of ceftazidime and cefoselis, were synthesized and their antibacterial activity against gram-positive and gram-negative was inspected.

Rhizobium nodM and nodN genes are common nod genes: nodM encodes functions for efficiency of nod signal production and bacteroid maturation.

Earlier, we showed that Rhizobium meliloti nodM codes for glucosamine synthase and that nodM and nodN mutants produce strongly reduced root hair deformation activity and display delayed nodulation of Medicago sativa (Baev et al., Mol. Gen. Genet. 228:113-124, 1991). Here, we demonstrate that nodM and nodN genes from Rhizobium leguminosarum biovar viciae restore the root hair deformation activity of exudates of the corresponding R. meliloti mutant strains. Partial restoration of the nodulation phenotypes of these two strains was also observed. In nodulation assays, galactosamine and N-acetylglucosamine could substitute for glucosamine in the suppression of the R. meliloti nodM mutation, although N-acetylglucosamine was less efficient. We observed that in nodules induced by nodM mutants, the bacteroids did not show complete development or were deteriorated, resulting in decreased nitrogen fixation and, consequently, lower dry weights of the plants. This mutant phenotype could also be suppressed by exogenously supplied glucosamine, N-acetylglucosamine, and galactosamine and to a lesser extent by glucosamine-6-phosphate, indicating that the nodM mutant bacteroids are limited for glucosamine. In addition, by using derivatives of the wild type and a nodM mutant in which the nod genes are expressed at a high constitutive level, it was shown that the nodM mutant produces significantly fewer Nod factors than the wild-type strain but that their chemical structures are unchanged. However, the relative amounts of analogs of the cognate Nod signals were elevated, and this may explain the observed host range effects of the nodM mutation. Our data indicate that both the nodM and nodN genes of the two species have common functions and confirm that NodM is a glucosamine synthase with the biochemical role of providing sufficient amounts of the sugar moiety for the synthesis of the glucosamine oligosaccharide signal molecules.

Ester-imine condensations: preparation of racemic intermediates for the synthesis of the carbapenem antibiotics PS-5 and PS-6.

The lithium enolates of ethyl butyrate and ethyl isovalerate react with N-p-methoxyphenylcinnamaldimine in tetrahydrofuran (THF)-hexamethylphosphoric triamide (HMPA) to afford predominantly trans beta-lactams 9 (67%) and 20 (78%), respectively. beta-Lactam 9 was converted to PS-5 intermediate 18 in 21% overall yield (8 steps). Beta-lactam 20 was converted to PS-6 analog 28 in 22% overall yield using an eight step sequence.