Dreef C E, Jansze J P, Elie C J, van der Marel G A, van Boom J H
Department of Chemistry, Leiden University, Netherlands.
Carbohydr Res. 1992 Oct 9;234:37-50. doi: 10.1016/0008-6215(92)85037-z.
(+/-)-2,3,6-Tri-O-benzyl-5-O-p-methoxybenzyl-myo-inositol and (+/-)-2,6-di-O-benzyl-5-O-p-methoxy-benzyl-myo-inositol, accessible readily from (+/-)-3,6-di-O-allyl-1,2-O-cyclohexylidene-myo-inositol, were phosphitylated with dibenzyl N,N-di-isopropylphosphoramidite, and the resulting phosphite triesters were oxidised with tert-butyl hydroperoxide to give the corresponding fully protected myo-inositol 1,4-bis- (12) and 1,3,4-tris-phosphate (13) derivatives. Cleavage of the p-methoxybenzyl group from 12 and 13, phosphonylation with bis[6-(trifluoromethyl)benzotriazol-1-yl] methylphosphonate or (difluoromethyl)phosphonic di(1,2,4-triazolide), followed by treatment in situ with benzyl alcohol, and then hydrogenolysis of the benzyl groups gave the 5-methylphosphonate and 5-[(difluoromethyl)phosphonate] analogues of myo-inositol 1,4,5-tris- and 1,3,4,5-tetrakis-phosphate. The 5-methylphosphonate analogue of myo-inositol 1,4,5-trisphosphate acted as a calcium antagonist in permeabilized human platelets.
(±)-2,3,6-三-O-苄基-5-O-对甲氧基苄基-myo-肌醇和(±)-2,6-二-O-苄基-5-O-对甲氧基苄基-myo-肌醇可从(±)-3,6-二-O-烯丙基-1,2-O-环己叉基-myo-肌醇轻松制得，它们用二苄基N,N-二异丙基亚磷酰胺进行亚磷酸酯化，所得亚磷酸三酯用叔丁基过氧化氢氧化，得到相应的完全保护的肌醇1,4-双(12)和1,3,4-三磷酸(13)衍生物。从12和13上裂解对甲氧基苄基，用双[6-(三氟甲基)苯并三唑-1-基]甲基膦酸酯或(二氟甲基)膦酸二(1,2,4-三唑化物)进行膦酰化，然后用苄醇原位处理，接着对苄基进行氢解，得到肌醇1,4,5-三磷酸和1,3,4,5-四磷酸的5-甲基膦酸酯和5-[(二氟甲基)膦酸酯]类似物。肌醇1,4,5-三磷酸的5-甲基膦酸酯类似物在通透的人血小板中起钙拮抗剂的作用。
