5- 25930, antibacterial agent, enantiomers

The antibacterial agent flumequine 280 was synthetized in optically active form by starting with resolution of the two enantiomers of a suitably substituted racemic tetrahydroquinoline through formation of the (lf )-3-bromocamphor-8-sulfonates. After N-alkylation of the (2K)-tetrahydroisoquinoline enantiomer 277 with diethyl ethoxymethylene-malonate to give 278, the quinolizidine system 279 was formed by acylation onto the peri-position. This compound was finally hydrolyzed to afford 280 (Scheme 60) <1999TA1079>. 

As is discussed at a later point in this review, it has been shown that the enantiomer (33) of ofloxacin [81] and the related enantiomer (34) of S-25930 [82] are each significantly more potent antibacterial agents than their respective enantiomers furthermore, the gem-dimethyl analogue (35) is as inactive as the... 

Quinolones possessing a 7-(3-aminopyrrolidin-l-yl) substituent are particularly potent antibacterial agents. However, they often have very low solubility. Based on the observations that the hydroxymethylpyrrolidine (38) is significantly more potent against bacteria than its enantiomer (39) (the hydroxymethyl substituent in (39) apparently has a deleterious effect on activity while the same substituent in (38) has little effect on potency based on comparisons with the unsubstituted pyrrolidine analogue (40)) [84] and the enantiomer (41) is at least as potent as,... 

P,4S,4 S)-Enantiomer of spiro[l,4]oxazino[4,3-a]quinoline 173 is a promising member of a novel class of antibacterial agents with novel mechanism of action (09JA3991). 

Optically active pipecolic acid and its derivatives can be prepared via 4-phenylpyrido[2,l-c][l,4]oxazin-l-one derivatives. Representatives of the third generation of quinoline-3-carboxylic acid antibacterial agents ofloxacin (19), its levorotatory enantiomer, levofloxacin (20), and rufloxacin (21) have gained wide acceptance for the treatment of bacterial infections of the respiratory and urinary tracts, skin, and soft tissues, as well as sexually transmitted diseases, and pazufloxacin (22) is under development. Other 10-aryl-9-fluoro-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-de]-l,4-benzox-azine-6-carboxylic acids and 7//-pyrido[l,2,3-de]-l,4-benzothiazine-6-carboxylic acids exhibit mammalian topoisomerase II inhibitory activity. 

The synthesis of (5 S)-thiolactomycin (792), an enantiomer of an antibacterial agent, makes use of a Wittig olefination early in the sequence as a way of preparing a,jS-unsaturated ester 786 (Scheme 106). The key step in the synthesis is an allyl xanthate-dithiocarbonate rearrangement of 788 to 789. This process occurs upon distillation of 788 at 145 °C (0.4 mm Hg) and gives the desired product 789 in nearly quantitative yield. Chirality transfer is equally efficient, with an enantiomeric excess of at least 98% [222]. 

Polyether lonophores. Isolation and identification of antibiotic X-14885A was reported.Its structure is closely related to A-23187 and cezomycin, members of the pyrrolether class of natural ionophores. Aspects of the discovery and ionophoric properties of the X-14868 complex were described. Another new naturally derived agent, CP-53607 (32), was reported to be effective t ainst coccidia and as a rumen propionic acid stimulant. The C-26 urethane analogs of monensin transported both Rb and Ca. Their antibacterial and anticoccidial activities were also reported as greater than monensin. Microbial conversion of grisorixin by Streptomyces rimosus was found to produce an inactive and detoxified product. A unified stereochemical model of polyether antibiotic structure and biogenesis was proposed. Ibtal synthesis of ionophores continued to be of interest and the unnatural enantiomer of lasalocid A was found to have similar biolc cal properties to the natural product. ... 

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