Pristinamycin reaction with acid chlorides

In contrast to the reaction of pristinamycin 11 with acid anhydrides, where acylation was only observed with acetic anhydride, the reaction of pristinamycin IIa with acid chlorides (Scheme 10) was demonstrated to be of greater synthetic utility. However, the course of acylation depended strongly on the reactivity of the acid chloride. For example, the reaction of pristinamycin 11 with ethyl malonyl chloride in the presence of triethylamine or pyridine resulted in a quantitative conversion by tic into the ester (50, R = CH2C02Et, 60% isolated yield) whereas the use of more reactive acyl chlorides, for example ethyl chloroformate resulted in acylation of the 37-ketone function as its enol ether (see Sect. 5.4.2). If the acylation reagents were used in excess, a diacylated derivative pf the enol form of pristinamycin 11 (51) was obtained. 

Acylations of the hydroxy function of the picolinic acid residue occurred readily using standard acylation procedures reaction of pristinamycin with acid chlorides or anhydrides in the presence of pyridine or triethylamine afforded the corresponding esters (15) and the use of N or 0-chlorocarbonyl reagents afforded carbamates or carbonates. 

A limited number of semi-synthetic 36-0-acyl pristinamycin 11 derivatives were prepared by acylation of the 36-hydroxy group with acid anhydrides or acid chlorides under classical acylation conditions [114]. In all cases the trienone (47) was formed as a byproduct (a large number of the reactions afforded the trienone as the only identifiable product), and isolation of the 36-0-acyl pristinamycin 11 derivatives was often difficult reflecting their ease of transformation into the trienone. 

Reaction of pristinamycin 11 with N-chlorocarbonyl reagents proceeded in a similar manner to the reaction with ethyl malonyl chloride, for example reaction with N-(chIorocarbonyl)isocyanate afforded after acidic work-up the carbamate (50, R = NH2) and reaction with iV-methylpiperazinylcarbonyl... 

---