Patent ID: 6344581
Filing Date: 2002-02-05
Classification: A61K,C07C,Y10S

Abstract:
A method of synthesizing a 9-halo-3-oxaprostaglandin from the lactone: wherein n=0 or 1, comprising:(a) reducing the lactone to yield a corresponding diol; (b) silylating the diol to yield a corresponding bissilyl ether; (c) selectively oxidizing the bissilyl ether to yield a monosilyloxy carboxaldehyde; (d) reacting the monosilyloxy carboxaldehyde with a trialkyl phosphonoacetate to yield a silyloxy &agr;, &bgr;-unsaturated ester; (e) reducing the silyloxy &agr;, &bgr;-unsaturated ester to yield a silyloxy allylic alcohol; (f) alkylating the silyloxy allylic alcohol to yield a silyloxy allyl carboalkoxymethyl ether; (g) desilylating the silyloxy allyl carboalkoxymethyl ether to yield a hydroxy allyl carboalkoxymethyl ether; (h) performing a halo substitution of the hydroxy allyl carboalkoxymethyl ether to yield a halo allyl carboalkoxymethyl ether; and (i) converting the modified hydroxy groups of the halo allyl carboalkoxymethyl ether to hydroxy groups to yield a 9-halo-3-oxaprostaglandin of the formula: â€ƒwherein: R1=CO2R2, wherein R2=H, a cationic salt moiety, or an ophthalmically acceptable ammonium moiety; or R1 represents an ophthalmically acceptable ester moiety; X=halogen in either configuration; and n=0 or 1.