11-deoxy-PGFi

The 11-deoxyprostaglandins, a group not found in nature, have been synthesised by workers at the Ayerst Laboratories [115, 148-151]. 11-Deoxy-PGFy (LXXI) has been prepared starting from the enone (LXXII), obtained by the action of sulphuric acid on the monobromo derivative of the condensation product of ethyl 2-cyclopentanone carboxylate and (o-bromoethylheptanoate [115, 148, 149]. Reaction of (LXXII) with acetone cyanohydrin, hydrolysis of the ester-nitrile to the dicarboxylic acid and reaction with methanol and />-toluenesulphonic acid gave the mono ester (LXXIII) of which the acid chloride was converted with heptyne and aluminium chloride into the chlorovinylketone (LXXIV). The sequence was then completed by replacement of chloro with methoxyl, ester hydrolysis and borohydride reduction to the unsaturated ketone (LXXV) followed by borohydride reduction of the side chain carbonyl group. 

A particularly useful feature of a route to 11-deoxy-PGFi (119), outlined by the May and Baker group (Scheme 24), is that it completely avoids the use of protecting groups. Catalytic hydrogenation of the 11-deoxy-PGFi affords an epimeric mixture of the corresponding 13,14-dihydro-compound. 

Scheme 12.5. Catalytic asymmetric synthesis of 1 l-deoxy-PGFi using a Noyori-type 3CR, by Shibasaki and co-workers [15].

Yamada K, Arai T, Sasai H, Shibasaki M. A catalytic asymmetric s3mthesis of ll-deoxy-PGFi using ALB, a heterobimetallic multifunctional asymmetric complex. J. Org. Chem. 1998 63(11) 3666 3672. 

Full details have been published of the syntheses of 13,14-dihydro-derivatives of 11 -deoxy-PGEi, -PGFi and -PGFi by the Ayerst group in Canada. The key step in these syntheses is the novel photoannelation reaction between the chlorovinyl ketone (122) and the substituted cyclopentenone (72) to give the cyclobutane (123) (Scheme 26). Treatment of this photoadduct with... 

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