Processes and novel intermediates for 11-oxa prostaglandin synthesis

A process for the preparation of 11-oxa prostaglandin analogs of formula I:

• 10
• 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 X—Y=(CH2)mY1, m=0-6,
• 11
• wherein:
• W=CH2, O, S(O)m, NR10, CH2CH2, CH═CH, CH2O, CH2S(O)m, CH═N, or CH2NR10;
• m=0-2;
• R=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 corresponding 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.