Pisiferic acid synthesis yield

Next step of this synthesis consisted in the conversion of alcohol (17) to pisiferic acid (1) and this has been described in Fig. (3). The alcohol (17) in hexane was treated with Pb(OAc)4 in presence of iodine at room temperature to obtain the epoxy triene (19) (51%) whose structure was confirmed by spectroscopy. Treatment of (19) with acetyl p-toluene-sulfonic in dichloromethane yielded an olefinic acetate (20) and this was hydrogenated to obtain (21). The compound (22) could be isolated from (21) on subjection to reduction, oxidation and esterification respectively. The conversion of (22) to (23) was accomplished in three steps (reduction with sodium borohydride, immediate dehydration in dichloromethane and catalytic hydrogenation). Demethylation of (23) with anhydrous aluminium bromide and ethanethiol at room temperature produced pisiferic acid (1). Similar treatment of (23) with aluminium chloride and ethanethiol in dichloromethane yielded methylpisiferate (3). 

The starting material for the present synthesis was the already described alcohol (171), prepared from the Wieland-Miescher ketone (1). It was converted to the ketone (182) by oxidation. Reduction of the ketone (182) yielded the alcohol (183) in 56% yield. Irradiation of a cyclohexane solution of the alcohol with lead tetra-acetate and iodine afforded the expected cyclic ether (184) in 45% yield, which on oxidation yielded the keto-ether (185). The formyl derivative prepared from the keto-ether on subjection to Robinson annelation with 4-diethylaminobutan-2-one methiodide following the procedure of Howell and Taylor [74] afforded the adduct (186). The adduct, when heated with sodium methoxide in methanol produced the tricyclic keto ether (187) whose H N.M.R. spectrum showed it to be a mixture of C-lOa epimers. The completion of the synthesis of pisiferic acid (196) did not require the separation of a and P-epimers and thus the keto ether (187) was used for the next step. 

An alternative route was also developed for the synthesis of ( )-pisiferic acid (196) as described in "Fig (17)". The starting material for the present synthesis was the already described alcohol (15), which on tetrahydropyranylation yielded the derivative (197). Metal hydride reduction of (197) afforded a mixture of alcohols whose tosyl derivative on heating with lithium bromide and lithium carbonate in dimethylformamide afforded the oily olefin (198). These conditions not only provoked the dehydrosulphonation but also the hydrolysis of the tetrahydropyranyl group, thus shortening the reaction sequence by one step. The oily olefin (198) on oxidation yielded the ketone (199), which was formylated, and subjected to Robinson annelation with methyl vinyl ketone prepared in situ following the procedure of Howell and Taylor [74]. The resulting adduct without purification was heated by boiling with sodium methoxide in methanol to obtain the tricyclic ketone (200). It was treated with... 

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