Synthesis of a 1,2-trans-Configurated, Equatorial Glycosylphosphonate Analogue of D-myo-Inositol 1,4,5-Trisphosphate

Article abstract of DOI:10.1002/hlca.19930760224

The diphosphonate analogue 3 of D-myo-inositol 1,4,5-trisphosphate (1), a 1,2-trans-configurated, equatorial glycosylphosphonate, was synthesized and characterized as its hexasodium salt 3a.In a first approach, the silylated galactal 4 (Scheme 1) was transformed into the oxirane 5 and hence, by treatment with Me3SiP(OMe)2, into a mixture of the glycosylphosphonate 6 and its silyl ether 7.This mixture was desilylated and then treated with acetone and FeCl3 to yield 8 and 9 (64 and 22percent, resp., from 4).In a second approach, the acetates 11/12 (Scheme 2) were treated with P(OMe)3/Me3SiOTf in MeCN to afford the anomeric glycosylphosphonates 16/17 (1:1, 60percent), while the trichloroacetimidate 10 gave mostly the α-D-anomer 16.The α-D-anomer 20 was obtained from 12 and P(OPh)3.The highest yield of a β-D-phosphonate was realized by treating 12 with the cyclic phosphite 15 ( -> 18/19, 40percent each).The β-D-phosphonate 17 was debenzylated ( -> 21) and protected to give 8.Transformation of 8 into the bromide 22 (43percent) proved difficult due to the facile demethylation of the phosphonate, and was best followed by treatment of the crude product with CH2N2 and 2,2-dimethoxypropane.Phosphorylation of 22 yielded 41percent of the (dimethoxyphosphoryl)phosphate 23.The conditions of the Arbuzov reaction slowly converted the bromide 23 into the bis(phosphoryl)phosphate 24 (69percent), which was then deprotected.The resulting 3 was purified via the ammonium salt and transformed into 3a (72percent).