Daniel Bouzard

Fluoronaphthyridines and quinolones as antibacterial agents. 2. Synthesis and structure-activity relationships of new 1-tert-butyl 7-substituted derivatives.

A number of 7-substituted-1-tert-butyl-6-fluoroquinolone-3-carboxylic acids and 7-substituted-1-tert-butyl-6-fluoro-1,8-naphthyridine-3-carboxylic acids have been prepared and tested for antibacterial activities. Among those the 7-aminopyrrolidinyl 20b and the 7-diazabicyclo naphthyridine 18b are the most potent compounds in vitro and in vivo. Physicochemical data and acute toxicity are also discussed. Compound 18b, BMY 40062, exhibits the most favorable overall properties, considering in vitro and in vivo microbiological activity, its low toxicity, and pharmacokinetic profile, and was selected for clinical evaluation.

Stereoselective addition reactions to chiral N-benzylidene-p-toluenesulfinamides. Application to the synthesis of optically active 1,2-diphenylethylamines

Abstract An efficient and enantiospecific synthesis of substituted 1,2-diphenylethylamines 5 from benzaldehydes is described using a recyclable chiral auxiliary.

Recent Advances in the Chemistry of Quinolones

Nalidixic acid was first introduced in therapy in 1963, about 15 years later a new generation of quinolones with broader spectrum of activity appeared: the fluoroquinolones; since then about 6000 new analogs have been disclosed and about 20 derivatives are marketed or in advanced development.

Synthesis and reactivity of a N-aryl-2-vinyltetrahydro-4-oxoquinoline

Abstract Ethyl 2-ethenyl-6,7-methylenedioxy-1,2,3,4,-tetrahydro-1-(3′,4′,5′-trimethoxyphenyl)-4-oxoquinoline-3-carboxylate 1 was prepared by the reaction of vinylcuprate on ethyl 1,4-dihydro-6,7-methylenedioxy-1-(3′,4′,5′-trimethoxyphenyl)-4-oxoquinoline-3-carboxylate 9. Different quinolones and a tetrahydro-4-oxoquinoline have been obtained by oxidation of 1. Depending on the reagent, the initial addition occurs either at only one of the reactive functions, namely the vinyl double bond or the enolate, or at both. New unexpected 1,2-dihydroquinolines were synthesized in attempts at protecting the diol obtained by reduction of 1.

Enantioselective synthesis of 1,2-acetonide of (2S,3R)-3-N-boc-3-amino-4-phenyl-1,2-butanediol

Abstract An efficient and stereocontrolled preparation of the (2 S ,3 R )-1,2-acetonide 15 , from hydrazone 10 , leading to a (D)-phenylalaninol derivative, potentially useful for the design of HIV protease inhibitors, is described.

4-Hydroxy-2-methyl-3(2H)-isothiazolone-1,1-dioxide as protecting group of 4-(N-methylaminosulfonyl)methylphenylhydrazine during Fischer indole synthesis

Abstract Protection of the benzylic position of 4-methylaminosulfonylmethylphenyl hydrazine 6 with a 4-hydroxy-2-methyl-3(2 H )-isothiazolone-1,1-dioxide group allowed the preparation of indole 3 without formation of side-product.

Synthesis of a new bridged diamine 3,6-diazabicyclo [3.2.0] heptane: Applications to the synthesis of quinolone antibacterials.

Abstract Diprotected 3,6-diazabicyclo [3.2.0] heptane has been prepared by an highly efficient process. Selective deprotection, followed by condensation with 7-halogenoquinolones led to the naphthyridones 10 and 13 and the quinolone 14 .

Studies Toward the Stereocontrolled Synthesis of a Key Azetidinone-Acid Intermediate in the Preparation of a New Carbapenem

Abstract An efficient and stereocontrolled preparation of the key a/etidinone-acid 5a is described.

Synthesis, in vitro and in vivo antibacterial activity of 7-(7-methyl-2,5-diazabicyclo [2.2.1]heptane) naphthyridone derivatives as analogs of BMY 40062

Abstract The synthesis and the antimicrobial activities of chiral (1 R ,4 R ,7 S )- and (1 S ,4 S ,7 S )-[7-methyl-2,5-diazabicyclo[2.2.1]-heptan-2-yl] analogs of BMY 40062 are reported. The new derivatives have been found to be less active in vitro but as active in vivo (im) than BMY 40062. The 1 R ,4 R ,7 S substituent seems promising for the design of powerful new antibiotics.

Synthesis of chiral α-substituted N-[((2S)-2-hydroxy-2-phenyl)-ethyl]-2-phenylglycine derivatives by diastereocontrolled alkylation of (6 R)-2,3,5,6-tetrahydro-3,6-diaryl-N-[(2′R)-(2′-methyl)phenyl-methyl]-4H-1,4-oxazin-2-ones

Abstract The synthesis of α-substituted N-[((2S)-2-hydroxy-2-phenyl)-ethyl]-2-phenylglycine derivatives is reported. The key step of the sequence is the highly diastereoselective alkylation of (6R)-2,3,5,6-tetrahydro-3,6-diaryl-N-[(2′R)-(2′-methyl)phenylmethyl]-4H-1,4-oxazin-2-ones after deprotonation with t-BuOK. Opening of the resulting oxazinone with ethanolic KOH, followed by hydrogenolysis of the corresponding N-[(2R)-(2-methyl)phenylmethyl] compound to furnish the expected 2-phenylglycine derivative, is also described.