合成路线:16-Methylprostaglandin PGF2alpha methyl ester (Ia-b) is cyclized with iodine/sodium bicarbonate to give (IIa-b),which is acetylated with acetic anhydride/pyridine to (IIIa-b).Dehydrohalogenation with DBN generates the protected PGI2 analogue (IVa-b),which reacts smoothly with chlorosulfonyl isocyanate (A) to afford the adduct (Va-b).Without isolation (Va-b) gives on treatment with triethylamine in acetonitrile or solvolysis with N,N-dimethylformamide (DMF) the stable protected 5-cyano analoque (VIa-b),which contains up to ca.5% Z-isomer,readily removed by chromatography.Finally,saponification affords the free ZK-34,798 (nileprost).
参考文献标题:Nileprost
文献作者:Hashimoto,S.
参考来源:Drugs Fut 1982,7(9),643
合成路线:A new synthesis of nileprost has been described: The condensation of the protected lactone (I) with acetonitrile by means of lithium dimethylamide (LDA) gives the cyanomethylene derivative (II),which is condensed with methyl 4-oxobutyrate (III) by means of the same reagent yielding compound (IV).The partial reduction of (IV) with H2 over Pd/C in toluene affords compound (V) with part of the nileprost skeleton.Partial deprotection of (V) with tetrabutylammonium fluoride gives the alcohol (VI),which is oxidized with SO3-pyridine complex to the aldehyde (VII).The Wittig condensation of (VII) with diethyl (2-oxo-3-methylheptyl)phosphonate (VIII) by means of NaH in THF yields the enone (IX),which is deprotected with acetic acid and reduced with diisobutylaluminum hydride in toluene to afford the nileprost methyl ester (X).Finally,this compound is hydrolyzed with NaOH in methanol-water.
参考文献标题:Highly stereoselective synthesis of exocyclic tetrasubstituted enol ethers and olefins.A synthesis of nileprost
文献作者:Takahashi,A.; Kirio,Y.; Sodeoka,M.; Sasai,H.; Shibasaki,M.
参考来源:J Am Chem Soc 1989,111(2),643
合成路线:16-Methylprostaglandin PGF2alpha methyl ester (Ia-b) is cyclized with iodine/sodium bicarbonate to give (IIa-b),which is acetylated with acetic anhydride/pyridine to (IIIa-b).Dehydrohalogenation with DBN generates the protected PGI2 analogue (IVa-b),which reacts smoothly with chlorosulfonyl isocyanate (A) to afford the adduct (Va-b).Without isolation (Va-b) gives on treatment with triethylamine in acetonitrile or solvolysis with N,N-dimethylformamide (DMF) the stable protected 5-cyano analoque (VIa-b),which contains up to ca.5% Z-isomer,readily removed by chromatography.Finally,saponification affords the free ZK-34,798 (nileprost).
参考文献标题:The synthesis of 16(R)- or 16(S)-methylprostaglandins
文献作者:Tanouchi,T.; Miyake,H.; Igushi,Y.; Hayashi,M.; Iguchi,S.
参考来源:J Org Chem 1973,381250-51
合成路线:16-Methylprostaglandin PGF2alpha methyl ester (Ia-b) is cyclized with iodine/sodium bicarbonate to give (IIa-b),which is acetylated with acetic anhydride/pyridine to (IIIa-b).Dehydrohalogenation with DBN generates the protected PGI2 analogue (IVa-b),which reacts smoothly with chlorosulfonyl isocyanate (A) to afford the adduct (Va-b).Without isolation (Va-b) gives on treatment with triethylamine in acetonitrile or solvolysis with N,N-dimethylformamide (DMF) the stable protected 5-cyano analoque (VIa-b),which contains up to ca.5% Z-isomer,readily removed by chromatography.Finally,saponification affords the free ZK-34,798 (nileprost).
参考文献标题:A synthesis of prostaglandin sodium salt
文献作者:Whittaker,N.
参考来源:Tetrahedron Lett 1977,2805-08
合成路线:16-Methylprostaglandin PGF2alpha methyl ester (Ia-b) is cyclized with iodine/sodium bicarbonate to give (IIa-b),which is acetylated with acetic anhydride/pyridine to (IIIa-b).Dehydrohalogenation with DBN generates the protected PGI2 analogue (IVa-b),which reacts smoothly with chlorosulfonyl isocyanate (A) to afford the adduct (Va-b).Without isolation (Va-b) gives on treatment with triethylamine in acetonitrile or solvolysis with N,N-dimethylformamide (DMF) the stable protected 5-cyano analoque (VIa-b),which contains up to ca.5% Z-isomer,readily removed by chromatography.Finally,saponification affords the free ZK-34,798 (nileprost).
参考文献标题:Reaktive isocyanate I.Sie direkte einfuehrung von nitrilgruppen in ungesattigte systeme.Eine einfache umwandlung von carbos鋟ren in ihre nitrile
文献作者:Vorbr黦gen,H.
参考来源:Tetrahedron Lett 1968,1631-34
合成路线:16-Methylprostaglandin PGF2alpha methyl ester (Ia-b) is cyclized with iodine/sodium bicarbonate to give (IIa-b),which is acetylated with acetic anhydride/pyridine to (IIIa-b).Dehydrohalogenation with DBN generates the protected PGI2 analogue (IVa-b),which reacts smoothly with chlorosulfonyl isocyanate (A) to afford the adduct (Va-b).Without isolation (Va-b) gives on treatment with triethylamine in acetonitrile or solvolysis with N,N-dimethylformamide (DMF) the stable protected 5-cyano analoque (VIa-b),which contains up to ca.5% Z-isomer,readily removed by chromatography.Finally,saponification affords the free ZK-34,798 (nileprost).
参考文献标题:Nitrilsynthesen mit chlorsulfonylisocyanat
文献作者:Lohaus,G.
参考来源:Chem Ber 1967,1002719-29
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