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Synthese eines 1,2‐ trans ‐konfigurierten, äquatorialen Glycosyl‐phosphonat‐Analogen von D ‐ myo ‐Inositol‐1,4,5‐trisphosphat
Author(s) -
Czollner LáSzló,
Baudin Gisèle,
Bernet Bruno,
Vasella Andrea
Publication year - 1993
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19930760224
Subject(s) - chemistry , anomer , phosphonate , bromide , stereochemistry , demethylation , yield (engineering) , formylation , glycosyl , trimethyl phosphite , medicinal chemistry , organic chemistry , catalysis , biochemistry , gene expression , materials science , metallurgy , dna methylation , gene
Synthesis of a 1,2‐ trans ‐Configurated, Equatorial Glycosylphosphonate Analogue of D ‐ myo ‐Inositol 1,4,5‐Trisphosphate 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 Me 3 SiP(OMe) 2 , into a mixture of the glycosylphosphonate 6 and its silyl ether 7 . This mixture was desilylated and then treated with acetone and FeCl 3 to yield 8 and 9 (64 and 22%, resp., from 4 ). In a second approach, the acetates 11/12 ( Scheme 2 ) were treated with P(OMe) 3 /Me 3 SiOTf in MeCN to afford the anomeric glycosylphosphonates 16/17 (1:1, 60%), 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 , 40% each). The β‐ D ‐phosphonate 17 was debenzylated (→ 21 ) and protected to give 8 . Transformation of 8 into the bromide 22 (43%) proved difficult due to the facile demethylation of thephosphonate, and was best followed by treatment of the crude product with CH 2 N 2 and 2,2‐dimethoxyporpane. Phosphorylation of 22 yielded 41% of the (dimethoxyphosphoryl)phosphate 23 . The conditions of the Arbuzov reaction slowly converted the bromide 23 into the bis(phosphoryl)phosphate 24 (69%), which was then deprotected. The resulting 3 was purified via the ammonium salt and transformed into 3a (72%).