Patent ID: 6441196
Filing Date: 2002-08-27
Classification: C07D,C07F

Abstract:
A process for the preparation of 11-oxa prostaglandin analogs of formula I: wherein:R is H or a pharmaceutically acceptable cationic salt moiety, or CO2R forms a pharmaceutically acceptable ester moiety R9O and R15O are the same or different and constitute a free or functionally modified hydroxy group; --- is a single or trans double bond; X=(CH2)q or (CH2)qO; q=1-6; and Y=a phenyl ring optionally substituted with alkyl, halo, trihalomethyl, alkoxy, acyl, or a free or functionally modified hydroxy or amino group; or Xâ€”Y=(CH2)mY1, m=0-6, â€ƒwherein: W=CH2, O, S(O)m, NR10, CH2CH2, CH&boxH;CH, CH2O, CH2S(O)m, CH&boxH;N, or CH2NR10; m=0-2; R10=H, alkyl, acyl; Z=H, alkyl, alkoxy, acyl, acyloxy, halo, trihalomethyl, amino, alkylamino, acylamino, OH; and ----=single or double bond; comprising:a) converting 1,4-anhydro-D-glucitol to the corresponding ortho ester; b) silylating the ortho ester to yield to the corresponding silyl ether; c) removing the ortho ester group of the silyl ether to yield to the corresponding triol; d) converting the triol to the corresponding acetonide; e) oxidizing the free OH group of the acetonide to yield to the corresponding ketone; f) converting the ketone to the corresponding unsaturated ester; g) hydrogenating the unsaturated ester to yield the saturated ester; h) reducing the saturated ester to yield to the corresponding alcohol; i) converting the alcohol to the corresonding sulfonate; j) reacting the sulfonate with cyanide to yield to the corresponding nitrile; k) oxidatively cleaving the acetonide grouping of the nitrile to yield to the corresponding nitrile aldehyde; l) converting the nitrile aldehyde to the corresponding enone; m) reducing the enone to yield to the corresponding alcohol having desirable and undesirable epimeric forms; n) silylating the alcohol to yield to the corresponding bis silyl ether; o) reducing the bis silyl ether to yield to the corresponding aldehyde; p) condensing the aldehyde to yield to the corresponding ester; q) desilylating the ester to yield to the corresponding end product; and r) removing undesirable epimeric form.