The asymmetric synthesis of β-lactam antibiotics -II. The first enantioselective synthesis of the carbacephalosporin nucleus.

The application of asymmetric ketene-imine cycloadditions to the first enantioselective synthesis of the carbacephalosporin nucleus is described.     

The synthesis of prostaglandin E1 and related substances

The authors describe in detail the conversion of 4 isometric exo-substituted bicyclo (3.1.0) hexanones 1a, 1b, 2a and 2b (R=CH3) to 4 prostaglandins of the E series, including crystalline dl-prostaglandin E1 (PGE1). Oxidative solvolysis of the keto esters 1a and 2a and of the desired keto acids 1a and 2a (R=H) according to the method of Just and Simonovitch resulted in a good yield of the mixture of vic-glycols of unrearranged carbon skeleton. The presence of dl-PGE1, or dl-8-iso PGE1 or their methyl esters was not detected in either case. Analysis of the unalkylated ketones 5a and 5b under the same and other conditions yielded unrearranged vic-glycols 6 as essentially the only product. A reaction sequence produced dl-8-isoprostaglandin E1, the 15-epimers of these prostaglandins, and dl-PGA1 and dl-PGB1 methyl esters.     

Design and synthesis of ansamycin antibiotics

Ansamycin antibiotics are a class of microbial metabolites that exhibit an array of biological activities. This review covers the synthetic chemistry and biological activity of benzenic ansamycins from 1989 to 2007. In the first section, synthetic approaches to the C15-benzene ansamycins (geldanamycin and related) are discussed. Access to the C17-benzene ansamycins (or ansatrienins) is disclosed in the second half of this article.     

Bioactive polymers 61. synthesis and characterization of some retard antibiotics

Ampicillin and chloramphenicol were coupled on xanthan by activation by dicyclohexyl-carbodiimide. Drug release from the support was studied in vitro for ampicillin, and in vitro and in vivo conditions for chloramphenicol.     

Nuclear analogs of β-lactam antibiotics I. The synthesis of 6β-amidocyclonocardicins

A synthesis of a cyclic analog of the β-lactam antibiotic nocardicin A and a new synthon for N-unsubstituted azetidinones is described.     

Micellar electrokinetic capillary chromatography of macrolide antibiotics. Separation of tylosin, erythromycin and their related substances.

The separation of tylosin by micellar electrokinetic capillary chromatography with a mixed micelle system is described. Good selectivity was obtained with sodium phosphate buffer (80 mM, pH 7.5) containing 20 mM sodium cholate and 7 mM cetyltrimethylammonium bromide (CTAB). This method permits tylosin to be separated from its closely related substances within 15 min. The influences of type of buffer, buffer pH, the concentrations of sodium cholate and CTAB were investigated. The robustness of the method was examined for tylosin by means of a full-fraction factorial design. Quantitative results are presented. Using a similar buffer system (80 mM sodium phosphate, pH 6.0, 20 mM sodium cholate and 5 mM CTAB), separation of erythromycin and its main related substances was also obtained. However, detection sensitivity and resolution are not sufficient for analysis of related substances in erythromycin commercial samples.     

Pursuing effective Gram-negative antibiotics: The chemical synthesis of negamycin

In this Digest paper, various approaches toward chemical synthesis of negamycin, a natural dipeptide-like antibiotic, were summarized. The strategy and tactics in each individual synthesis were highlighted. Although the chemical structure of negamycin is relatively simple, the promising bioactivity against Gram-negative bacteria with a novel mechanism of action renders it as an intriguing lead compound for medicinal development.     

The efficient synthesis of chiral key intermediates for monobactam antibiotics

Chemical asymmetric syntheses of the key intermediates (4,6,8) for the synthesis of monobactam antibiotics (SQ 26776 (azthreonam), sulfazecin, and SQ 26180) are accomplished from (±)-4-phenylsulfonyl-2-azetidinone.     

The application of highly stereoselective aldol condensations to the synthesis of β-lactam antibiotics.

Stereoselective aldol condensations of fully protected glycine and 3-butyryl thiazolidine-2-thiones with achiral aldehydes afforded β-hydroxyesters suitable for elaboration to key intermediates for the synthesis of β-lactam antibiotics.