Stereospecific synthesis of antitumor active thioether PAF analogs.
Stereospecific synthesis of antitumor active thioether PAF analogs.
复制标题
抗肿瘤活性硫醚 PAF 类似物的立体定向合成。
作者：
Bhatia,SK;Hajdu,J
A novel stereospecific synthesis of antitumor active thioether analogs of platelet‐activating factor (PAF) is reported. The synthesis is based upon: i) the use ofD‐serine to provide the chiral center for the construction of the optically active phospholipid molecule; ii) development of thesn‐1‐thioalkyl function via thioacetate displacement of methanesulfonate‐activated primary hydroxyl group followed by alkylation of thesn‐1‐thiolate function; and iii) introduction of the phosphocholine moiety through the 2‐chloro‐2‐oxo‐1,3,2‐dioxaphospholane/trimethylamine sequence. The entire scheme relies on the use of a single protecting group. The synthetic thioether phospholipid 1‐S‐hexadecyl‐2‐N‐acetamidodeoxy‐sn‐glycero‐3‐phosphocholine has been shown to be a potent antitumor active phospholipid, exhibiting tumor cytotoxicity against a lymphoblastoid lymphoma (Li‐A) cell line and a malignant histiocytic (DHL‐4) cell line of human origin at the same level of potency as ET‐18‐OMe and 1‐O‐octadecyl‐2‐N‐acetamidodeoxy‐sn‐glycero‐3‐phosphocholine. The synthetic method described has a great deal of flexibility, providing a convenient general route to a wide range of thioether PAF analogs.
