Hemi-synthesis of three new armed antibiotics analogs of Calcimycin (A23187) and determination of theirs acidity constants by potentiometric method

A new series of three calcimycin derivatives cd3,cd5 and cd7 have been synthesizedby the condensation reaction of calcimycin (a23187) with ethyl 5-chloro-5-oxopentanoate,ethyl 7-chloro-7-oxoheptanoate and 9-chloro-9-oxononanoate in an equimolar ratio. the potentiometric studies show the presence of four species following the increase in ph,lh3+,lh2,lh- and l2-. we used a preferment program of simulation hyperquad which is very fast and gives acidity constants with a good correlation coefficient σ. distribution curves show a good predominance of the species lh2 for all analogues at biological ph. adjunction of aliphatic carboxylic arm at the benzoxazole nitrogen dramatically increases the acidity of the carboxylic function of 3 log units,which is enormous. this is mainly due to the attractive effect of the amide in α benzoxazole group,which relocates the link,than the aliphatic carboxylic function. profile structure are reinforced by three binding sites,the benzoxazole group by the mean of the carboxylic function and the pyrazole nitrogen and acetopyrole group by the intermediary of the keto function. the hydrogen bond breaking-established in two sides around of the benzoxazole group by steric hindrance may also explain the increased acidity of the acid function of the benzoxazole moiety. the spectroscopic data (ir nmr) and crystallographic study confirm these findings.