IsoPilopic acid

An a-D-glucopyranoside derivative (14) has been converted into + )- R)-2,3-bisacetoxymethylpentyl acetate (15) by conventional carbohydrate reactions. Compound (15) has also been previously obtained by lithium aluminium hydride reduction of (-H )-isopilopic acid (16) followed by acetylation. Furthermore, it has been established that the configurations at C-4 in (16) and in pilocarpine (13) are the same, but that the configuration at C-3 differs in the two compounds. Thus since compound (15) was shown to possess the (f )-configuration, the configurational assignment (3S,4/ ) for pilocarpine (13) is confirmed. 

The structures assigned to the alkaloids and their breakdown products on the basis of the degradative evidence have been confirmed by the S3Tithetic investigations of N. A. and W. A. Freobrashenski and their collaborators. The first step, the synthesis of pilopic and isopilopic acids, was achieved in 1930 by A. E. Tschitschibabin and N. A. Freobrashenski... 

N. A. Freobrashenski (69). On resolution through the strychnine salt, the d- and i-forms were obtained, the former being identical with d-iso-pilopic acid obtained by the oxidation of isopilocarpine and purified through the strychnine salt. The solid ester (XXXIII) similarly gave dZ-pilopic acid, which is readily isomerized to dZ-isopilopic acid when heated (61). It was resolved through the brucine and cinchonine salts (62). 

A. N. Dey (174) has described an independent synthesis of the alkaloids. Michael condensation of ethyl 7-ethoxy- or 7-phenoxy-crotonate (LI, R = OEt, R = Et or Ph) with ethyl malonate or cyan-acetate, followed by ethylation and hydrolysis, furnished a mixture of the two racemic forms of the glutaric acid, LII, which were separated by virtue of their different ease of anhydride formation. On treatment with hydrobromic acid, they gave rise to dl-homopilopic acid and dl-homo-isopilopic acid (LIII, R = OH), respectively. Corresponding methyl ketones (LIII, R = Me) were obtained by a similar synthesis from... 

Isopilopic acid, A28.18 Cyclopentane-1,3-dicarboxylic acid, A"30.4 C7H10O5... 

Isopilopic acid, A28 Labdanolic acid, T36 -longifolic acid, T28... 

---