合成路线1

13) The synthesis of the 17,18-ditritiated clinprost can be performed as follows: The reduction of the bicyclic aldehyde (LIII) described in Scheme 4 with NaBH4 in methanol gives the hydroxymethyl derivative (CXIII), which is esterified with methyl chloroformate yielding the carbonate ester (CXIV). The condensation of (CXIV) with 4,4-bis(phenylsulfonyl)butyric acid methyl ester (XCV) catalyzed by a palladium complex in THF affords the expected alkylation product (CXV), which is treated with Mg in methanol to eliminate the phenylsulfonyl groups, giving the unsaturated pentanoic acid methyl ester derivative (XLV) already obtained in Scheme 3. The desilylation of (XLV) with TBAF followed by oxidation with SO3/Pyr yields the aldehyde (XLVI), also reported in Scheme 3. The reaction of (XLVI) with dimethyl 2-oxo-4(Z)-heptenylphosphate (CXVI) by means of NaH in THF affords the expected condensation product (CXVII), which is regioselectively reduced with LiAlH4 in THF in the presence of (S)-(-)-binaphthol to give the (Z)-17,18-didehydro-11-O-tetrahydropyranylclinprost (CXVIII). Elimination of the THP group of (CXVIII) with acetic acid in THF/water yields the (Z)-17,18-didehydroclinprost (CXIX), which is finally tritiated by hydrogenation with tritium gas in benzene/cyclohexane using tris(triphenylphosphine)rhodium(I) chloride as catalyst. 14) If the final reduction of (CXIX) is performed with hydrogen gas in benzene/cyclohexane containing cyclododecene and in the presence of a Pd/C catalyst, clinprost is obtained.