Stefano Biondi

Highly Diastereoselective Synthesis of 4-N-Methylformamidino Trinem (GV129606), a Potent Antibacterial Agent

Abstract In this paper a highly diastereoselective synthesis of 4-N-methylformamidino trinem 3 is reported. The route offers advantages compared to that previously used, i.e. the higher overall yield, the robustness, the avoidance of toxic reagents. Most of the compounds were isolated by precipitation, therefore reducing the number of chromatographic separations. The efficient conversion of 4-N-methylamino trinem 11 into GV129606 3, was obtained by a new methodology in which a scavenger resin was used. The route presented in this paper allowed the preparation of the material required for early development studies and demonstrates the versatility of cyclohexenyl azetidinone 12 in the synthesis of 4-substituted trinems.

Synthesis and biological evaluation of 4-alkoxy substituted trinems. Part I

Abstract Synthesis of new 4-alkoxy substituted trinems 4, 5, 6, 7 and 8 together with their antibacterial profiles compared to imipenem and GV104326 ( 2 ) are described. The good antibacterial profile observed for derivatives 4–7 encouraged further exploration of these derivatives.

Synthesis and biological activity of novel tricyclic β-lactams

Abstract The synthesis and the preliminary data on microbiological activity of some tricyclic β-lactam derivatives ( 4 ), analogues of synthetic “trinems”, is described. Compound 14 , key intermediate in the synthesis of 18 , was stereoselectively obtained from its unsubstituted analogue, 12b , in 4 steps through enolphosphate 13 .

SYNTHESIS AND BIOLOGICAL EVALUATION OF 4-ALKOXYSUBSTITUTED TRINEMS. PART II

Abstract The synthesis and the microbiological evaluation of a novel series of substituted tricyclic β-lactam derivatives (trinems, former named tribactams) is reported. Suitable basic groups were introduced within the key C-4 side chain with the aim of improving the antibacterial activity of this class of new antibiotics to Pseudomonas spp.. Among the different compounds prepared, basic derivatives 2 and 3 showed improved activity with respect to GV 104326 1 against these highly resistant strains.

Synthesis and Structure-Activity Relationships of α-Amino-γ-lactone Ketolides: A Novel Class of Macrolide Antibiotics.

An efficient synthesis of α-amino-γ-lactone ketolide (3) was developed, which provided a versatile intermediate for the incorporation of a variety of aryl and heteroaryl groups onto the C-21 position of clarithromycin via HBTU-mediated amidation. The biological data for this important new class of macrolides revealed significantly potent activity against erythromycin-susceptible strains as well as efflux-resistant and erythromycin MLSB-resistant strains of S. pneumoniae and S. pyogenes. In addition, ketolide 11o showed excellent in vitro antibacterial activity against H. influenzae strain as compared to telithromycin. These results indicate that C-21 substituted γ-lactone ketolides have potential as a next generation macrolide antibiotics.

Synthesis and antibacterial activity of some thio trinems

Abstract The synthesis and antibacterial activity of some trinems having a sulfur atom in various positions of ring C are presented.

Synthesis and antibacterial, activity of 4-ureido trinems

Abstract This article describes studies carried out on the synthesis and biological activity of 4-ureido trinems 1 obtained by the condensation of various isocyanates and the intermedite 6. Among others, 4-N-methyl-N-alkyl ureido trinems showed a promising antimicrobial activity against Gram-negative bacteria.

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF TRINEMS BEARING NITROGEN DERIVATIVES AT C(4)

Optimization of the antibacterial activity of 4-amino trinem, obtained through chemical modification of the basicity of the amino group at position 4, has led to the identification of a very interesting compound characterized by a broad spectrum of activity includingPseudomonas aeruginosa.