新产品编号:1229723
Chemical Name:
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合成路线:The cyclization of L-serine (I) with pivalaldehyde (II) by means of LDA in THF gives the oxazolidine (III),which is acylated with formic and acetic anhydride yielding the N-formyloxazolidine (IV).The reaction of (IV) with LDA affords the chiral enol (V),which is treated with allyl bromide in THF to give the chiral 4-allyloxazolidine (VI).Cleavage of the oxazolidine ring with acetyl chloride and treatment with benzyl chloroformate yields the protected chiral 2-allylserine (VII),which is oxidized with oxalyl chloride to the corresponding aldehyde (VIII).The Wittig condensation of (VIII) with triphenylphosphoranylideneacetic acid methyl ester (IX) affords the intermediate (X),which is submitted to UV irradiation with an Hanovia medium pressure mercury lamp through a Pyrex filter in benzene containing benzophenone.A mixture of isomeric bicyclic compounds from which the desired compound (XI) is isolated by column chromatography.The hydrogenation of (IX) with H2 over Pd/C in methanol provides the bicyclic aminoester (XII),which is finally hydrolyzed with 6N HCl.
📌 参考资料/链接：
参考文献标题:Synthesis and biology of the conformationally restricted ACPD analogue,2-aminobicyclo[2.1.1]hexane-2,5-dicarboxylic acid-I,a potent mGluR agonist
文献作者:Kozikowski,A.P.; Steensma,D.; Araldi,G.L.; Tuckmantel,W.; Wang,S.; Pshenichkin,S.; Surina,E.; Wroblewski,J.T.
参考来源:J Med Chem 1998,41(10),1641
📄 详细内容
合成路线:The cyclization of L-serine (I) with pivalaldehyde (II) by means of LDA in THF gives the oxazolidine (III),which is acylated with formic and acetic anhydride yielding the N-formyloxazolidine (IV).The reaction of (IV) with LDA affords the chiral enol (V),which is treated with allyl bromide in THF to give the chiral 4-allyloxazolidine (VI).Cleavage of the oxazolidine ring with acetyl chloride and treatment with benzyl chloroformate yields the protected chiral 2-allylserine (VII),which is oxidized with oxalyl chloride to the corresponding aldehyde (VIII).The Wittig condensation of (VIII) with triphenylphosphoranylideneacetic acid methyl ester (IX) affords the intermediate (X),which is submitted to UV irradiation with an Hanovia medium pressure mercury lamp through a Pyrex filter in benzene containing benzophenone.A mixture of isomeric bicyclic compounds from which the desired compound (XI) is isolated by column chromatography.The hydrogenation of (IX) with H2 over Pd/C in methanol provides the bicyclic aminoester (XII),which is finally hydrolyzed with 6N HCl.
参考文献标题:Stereoselektive Alkylierung an C(alpha) von Serin,Glycerins鋟re,Threonin und Weins鋟re 黚er heterocyclische Enolate mit exocyclischer Doppelbindung
文献作者:von Diester,S.; et al.
参考来源:Helv Chim Acta 1987,701194-1216