Pettit George R, Melody Noeleen, Herald Delbert L
Cancer Research Institute and Department of Chemistry and Biochemistry, Arizona State University, PO Box 872404, Tempe, Arizona 85287-2404, USA.
J Nat Prod. 2004 Mar;67(3):322-7. doi: 10.1021/np030299+.
Selective phosphorylation of phenpanstatin (3a) with tetrabutylammonium dihydrogen phosphate and dicyclohexylcarbodiimide in pyridine followed by cation-exchange chromatographic procedures was found to provide an efficient route to a new series (3b-3d) of promising 3,4-O-cyclic phosphate prodrugs designated phenpanstatin phosphates. Application of analogous reaction conditions to pancratistatin (1a) led to a mixture of monophosphate derivatives where sodium pancratistatin 4-O-phosphate (4a) was isolated and the structure confirmed by X-ray crystallography. Modification of the reaction conditions allowed direct phosphorylation of pancratistatin followed by cation-exchange chromatography to afford sodium pancratistatin 3,4-O-cyclic phosphate (5a), which was selected for preclinical development.
在吡啶中用磷酸二丁铵和二环己基碳二亚胺对苯并菲他汀（3a）进行选择性磷酸化，然后通过阳离子交换色谱法，发现这为通往一系列新的（3b - 3d）有前景的3,4 - O - 环磷酸酯前药（称为苯并菲他汀磷酸盐）提供了一条有效途径。将类似的反应条件应用于 pancratistatin（1a），得到了单磷酸酯衍生物的混合物，其中分离出了pancratistatin 4 - O - 磷酸钠（4a），并通过X射线晶体学确定了其结构。对反应条件进行修改，使pancratistatin直接磷酸化，然后通过阳离子交换色谱法得到pancratistatin 3,4 - O - 环磷酸钠（5a），它被选用于临床前开发。
