Stereocontrolled Synthesis of a Trihydroxylated A Ring as an Immediate Precursor to 1α,2α,25‐Trihydroxyvitamin D3.
Stereocontrolled Synthesis of a Trihydroxylated A Ring as an Immediate Precursor to 1α,2α,25‐Trihydroxyvitamin D3.
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作为 1α,2α,25-三羟基维生素 D3 直接前体的三羟基化 A 环的立体控制合成。
DOI：
10.1002/chin.199147277
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
T. Nelson
中科院分区：
文献类型：
--
作者：
G. Posner;T. Nelson
3-溴-2-吡喃酮（1）在温和的热条件下与间二氧杂环戊烯2进行反电子需求Diels-Alder环加成反应，分离出功能和立体化学丰富的双环加成物endo-3，endo-3转化为三羟基化的A环烯丙基氧化膦，直接生成1a，2 a，25-三羟基维生素D3。25-二羟维生素D3（骨化三醇）1是细胞分化和增殖2以及肠钙和磷吸收和骨钙动员的有效调节剂。骨化三醇目前用于骨质疏松症的临床治疗和某些代谢紊乱如新生儿低钙血症、慢性肾功能衰竭和甲状旁腺功能减退症的化疗。3国际上正在开发各种具有修饰的D环侧链的骨化三醇类似物，用于银屑病的化学治疗，银屑病是一种以皮肤细胞过度增殖为特征的疾病。4.然而，相比之下，A环的制备工作相对较少。
3-Bromo-2-pyrone (1) was coaxed into inverse-electron-demand Diels-Alder cycloaddition with dioxole 2 under sufficientlymild thermal conditions to allow isolation of functionally and stereochemically rich bicycloadduct endo-3 that was transformed into tri-hydroxylated A-ring allylic phosphine oxide as an immediate precursor to la, 2a, 25-trihydroxyvitamin D3.Metabolic hydroxylation of vitamin D3 produces la, 25-dihydroxyvitamin D3 (calcitriol) 1 that is a potent regulator of cell differentiation and proliferation2 as well as intestinal calcium and phosphorus absorption andbone calcium mobilization. Calcitriol is used currently for clinical treatment of osteoporosis and for chemotherapy of certain metabolismdisorders such as neonatal hypo-calcemia, chronic renalfailure, and hypoparathyroidism. 3 Various calcitriol analogues havingmodified D-ring side chains are being developed internationally for chemo-therapy of psoriasis, a disease characterized by hyperproliferation of skin cells. 4 In comparison, relatively little effort, however, has been devoted to preparing ring-A