Cornella Iván, Suárez Rosa M, Mouriño Antonio, Sestelo José Pérez, Sarandeses Luis A
Departamento de Química Fundamental, Universidade da Coruña, E-15071 A Coruña, Spain.
J Steroid Biochem Mol Biol. 2004 May;89-90(1-5):19-23. doi: 10.1016/j.jsbmb.2004.03.045.
The synthesis of vitamin D(3) active metabolites [24R,25-(OH)(2)-D(3), 24S,25-(OH)(2)-D(3) and 1alpha,24R,25-(OH)(3)-D(3)] and the first 24-aminovitamin D(3) derivatives [24S-benzoylamino-25-OH-D(3) and 24S-benzoylamino-1alpha,25-(OH)(2)-D(3)] are reported. The stereogenic center at C-24 was generated through ultrasonically induced aqueous conjugate addition of iodide 8 to dioxolanone 6 or oxazolidinone 7. The vitamin D triene system was constructed using the Lythgoe approach. The synthetic route, which is both short (6 or 7 steps from iodide 8) and efficient (32-45% overall yield), constitutes a practical method for the preparation of 24-functionalized metabolites and analogues of vitamin D(3). The ultrasonically induced conjugate addition in the key step provides a novel example of a highly stereoselective reaction promoted by the zinc-copper couple in aqueous media.
报道了维生素D(3)活性代谢物[24R,25-(OH)(2)-D(3)、24S,25-(OH)(2)-D(3)和1α,24R,25-(OH)(3)-D(3)]以及首批24-氨基维生素D(3)衍生物[24S-苯甲酰氨基-25-OH-D(3)和24S-苯甲酰氨基-1α,25-(OH)(2)-D(3)]的合成。C-24位的手性中心是通过超声诱导碘化物8与二氧戊环酮6或恶唑烷酮7进行水相共轭加成反应生成的。维生素D三烯体系采用利思戈方法构建。该合成路线简短（从碘化物8出发6或7步）且高效（总收率32-45%），为制备24-官能化维生素D(3)代谢物及类似物提供了一种实用方法。关键步骤中的超声诱导共轭加成反应是锌铜偶在水相介质中促进的高立体选择性反应的一个新实例。
