Final Demonstration of the Co-Identity of Lipiarmycin A3 and Tiacumicin B (Fidaxomicin) through Single Crystal X-ray Analysis.

Lipiarmycin A3 and tiacumicin B possess the same chemical structure and have been considered identical till recently, when some authors have suggested the possibility of a minor difference between the chemical structures of the two antibiotics. In this work we performed a comparative X-ray analysis of lipiarmycin A3 and tiacumicin B. Although the commercial samples of the aforementioned compounds crystallize into two different crystal systems-evidently due to the different crystallization conditions-their chemical structures are identical.

The Co-identity of Lipiarmycin A3 and Tiacumicin B.

The co-identity of the antibiotics lipiarmycin A3 obtained from Actinoplanes deccanensis and tiacumicin B obtained from Dactylosporangium aurantiacum was unambiguously demonstrated through a number of experimental means. Spectroscopic analyses performed on both the antibiotics themselves and on their derivatives showed no difference between the two series of compounds. Moreover, unambiguous confirmation of the postulated identity of the two compounds was achieved by chemical degradation of lipiarmycin A3 and isolation of (3S,4R)-pentane-1,3,4-triol triacetate whose relative configuration was assigned by comparison with the authentic erythro and threo pentane-1,3,4-triol triacetates, obtained by chemical synthesis.

The co-identity of lipiarmycin A3 and tiacumicin B.

The co-identity of the antibiotics lipiarmycin A3 obtained from Actinoplanes deccanensis and tiacumicin B obtained from Dactylosporangium aurantiacum was unambiguously demonstrated through a number of experimental means. Spectroscopic analyses performed on both the antibiotics themselves and on their derivatives showed no difference between the two series of compounds. Moreover, unambiguous confirmation of the postulated identity of the two compounds was achieved by chemical degradation of lipiarmycin A3 and isolation of (3S,4R)-pentane-1,3,4-triol triacetate whose relative configuration was assigned by comparison with the authentic erythro and threo pentane-1,3,4-triol triacetates, obtained by chemical synthesis.

Synthesis and structure-activity relations in the class of 2-(pyridyl)penems.

The isosteric CH----N substitution in the class of 2-arylpenems results in improved antibacterial activity, with retention of the favorable characteristic of stability towards renal dehydropeptidase. High therapeutic efficacy was demonstrated in experimental mice septicemias with the 2-(3-pyridyl) derivative 2b and its orally absorbed acetoxymethyl ester prodrug 4n.