A novel glycopeptide carrying a 3-oxazolin-5-one ring obtained by intra-molecular cyclization.

The structure of a product, isolated during the synthesis of the semisynthetic glycopeptide MDL 63,246, was elucidated on the basis of spectroscopic methods and proved to be a novel glycopeptide containing a 3-oxazolin-5-one ring between positions 36 and 38. Subjected to acid hydrolysis this compound gave the corresponding pseudo aglycone and aglycone derivatives which maintained the original oxazolinone structure. Tested for antibacterial activity, these compounds showed a moderate activity against Gram-positive and inactive against Gram-negative bacteria.

Isolation and structure elucidation of 7,8-dideoxy-6-oxo-griseorhodin C produced by Actinoplanes ianthinogenes.

A novel product, isolated from a culture broth of Actinoplanes ianthinogenes fermented for producing purpuromycin, was purified and its structure established on the basis of physico-chemical data and chemical reactions. The new product resulted to be structurally related to griseorhodins, a group of hydroquinonic antibiotics obtained from Streptomyces californicus. This compound showed a weak activity against Gram-positive and resulted inactive against Gram-negative bacteria and Candida albicans.

Semisynthetic derivatives of purpuromycin as potential topical agents for vaginal infections.

Purpuromycin (1) is an antibiotic with a broad spectrum of antimicrobial activity, encompassing bacteria, fungi, and protozoa, particularly those involved in vaginal infections. With the aim of enhancing the solubility and reducing the serum binding, a chemical program of modifications was undertaken on the natural compound, and a new interesting series of derivatives at the naphthoquinone system was synthesized and evaluated as potential topical agents for vaginal infections. In particular three semisynthetic derivatives, 7'-amino (8a), 7'-methylamino (8b), 7'-ethylamino (8c), of 7'-demethoxypurpuromycin seemed to be the most promising. They were tested for in vitro activity against three of the most important vaginal pathogens and showed activity similar to that of purpuromycin against Candida isolates while they were significantly more active against Trichomonas vaginalis and Gardnerella vaginalis, which are cultured in media containing blood or serum. This is probably due to the fact that the activity of the derivatives is less antagonized by these supplements than that of purpuromycin.

Polymorphism-structure relationships of rifamexil, an antibiotic rifamycin derivative.

The polymorphism of rifamexil, a rifamycin derivative, has been investigated by thermomicroscopy, differential thermal analysis (differential scanning calorimetry-thermogravimetry), IR spectroscopy, and X-ray powder diffraction. Two crystalline forms, an amorphous material, and three solvates have been studied. The crystal structures of two solvates have also been determined by single-crystal X-ray techniques. Although the overall conformation of rifamexil is very similar in the two compounds, marked differences occur between the two crystal packings, due to differences both in the mutual orientation of the molecules and in the rifamexil-solvent interactions. Multivariate statistical methods have been used to identify the principal structural parameters determining the biological activity of the rifamycins.

Isolation and structure determination of the main related substances of teicoplanin, a glycopeptide antibiotic.

Teicoplanin is a complex formed by five closely related glycopeptides and by a small amount of a hydrolysis product. Minor quantities of related substances are also present. Two of them (named RS-1 and RS-2) were isolated and purified starting from the tailing fractions of a teicoplanin batch. Preparative reversed-phase liquid chromatography on large low-pressure and medium high-pressure scales, concentration, desalting, and freeze-drying steps were applied. 300 mg of RS-1 and 900 mg of RS-2 were obtained in a purity grade (about 90%) sufficient for structural investigation. Starting from considerations on the HPLC retentivity and on biosynthesis, the structures were assigned on the basis of 1H-N.M.R. spectra and homonuclear CO-SY 2D experiments, FAB-MS spectrometry, and GC-MS of the esters of the fatty acids obtained by hydrolysis. RS-1 and RS-2 are teicoplanins having 10-methyl-undecanoic acid and n-dodecanoic acid, respectively as fatty acid chains. No major difference in the in vitro activity of these teicoplanins emerged in comparison with teicoplanin complex.

Antiinflammatory properties of a series of 4-amino-5-arylpyrazoles.

A series of ethyl 4-amino-5-arylpyrazol-3-yl carboxylates were prepared from arylacetonitriles and ethyl diazoacetate. The compounds were evaluated for their analgesic and antiinflammatory properties, that were not, however, sufficiently interesting to justify the further development of the compounds. The synthesis of the compounds could be a useful extension of the original report by A. Bertho on the reaction between ethyl cyanoacetate and ethyl diazoacetate to yield diethyl 4-aminopyrazole-3,5-dicarboxylate.

Synthesis and pharmacological evaluation of a series of analgesic and antiinflammatory 4-aminopyrroles.

The synthesis and the pharmacological evaluation of a series of analgesic, antiinflammatory beta-aminopyrroles is described. Qualitative structure activity relationships are discussed. One of the compounds reported in the study is a candidate for toxicological and clinical trials.

Synthesis and anti-inflammatory properties of some pyrrolo(1H,3H)[3,4-d]pyrimidin-2-ones and pyrrolo(1H,6H)[3,4-d]pyrimidin-2-ones.

The unequivocal synthesis of some terms belonging to the two isomeric classes of the pyrrolo(1H,3H)[3,4-d]pyrimidin-2-ones and of the pyrrolo(1H,6H)[3,4-d]pyrimidin-2-ones is reported. Some of these compounds are active in inhibiting the development of the carrageenin edema, of the granuloma cotton pellet and of the adjuvant arthritis in the rat when administered orally.

Synthesis and pharmacological properties of derivatives of pyrrolo(3,4-d)pyrimidines and pyrrolo(3,4-b)pyridines (I).

The synthesis of variously substituted pyrrolo[3,4-d]pyrimidines and pyrrolo[3,4-b]pyridines is reported. Some of the compounds act as reducers of the carrageenin edema in the rat and as inhibitors of prostaglandin biosynthesis in a microsomal preparation of bovine seminal vesicles.