Chodyński M, Wojciechowska W, Halkes S J, van de Velde J P, Kutner A
Pharmaceutical Research Institute, Warsaw, Poland.
Steroids. 1997 Jul;62(7):546-53. doi: 10.1016/s0039-128x(97)00040-8.
A synthesis and an in vitro evaluation of side chain-unsaturated analogs 3 and 4 of 24a, 24b-dihomo-1,25-dihydroxycholecalciferol (1) are described, Novel C23a, 24-vitamin D synthons (sulfone 10 and aldehyde 11) were used for the synthesis of analog 4 and for the efficient preparation of the parent compound 1. The synthetic approach developed allows the use of easily available side chain fragments, such as oxirane 12 or Wittig reagent 15 for the preparation of compound 1 and analog 4, respectively. Introduction of a 24aE double bond results in a selective, 1000-fold increase in the binding affinity of analog 4 for the vitamin D receptor, compared to the affinity of 1, whereas the affinity of 4 for the vitamin D-binding protein and the activity in stimulating the differentiation of human promyelocytic leukemia HL-60 cells remained largely unchanged.
本文描述了24a, 24b-双高-1,25-二羟基胆钙化醇(1)的侧链不饱和类似物3和4的合成及其体外评价。新型C23a, 24-维生素D合成子(砜10和醛11)用于合成类似物4以及高效制备母体化合物1。所开发的合成方法允许分别使用易于获得的侧链片段，如环氧乙烷12或维蒂希试剂15来制备化合物1和类似物4。引入24aE双键导致类似物4对维生素D受体的结合亲和力与1相比选择性地增加了1000倍，而4对维生素D结合蛋白的亲和力以及刺激人早幼粒细胞白血病HL-60细胞分化的活性基本保持不变。
