Glycosylphosphonates of 2‐Amino‐2‐deoxy‐aldoses. Synthesis of a Phosphonate Analogue of Lipid X

Abstract

A preparation of glycosylphosphonates (27,28,36,38, and 39) from 2-azido-2-deoxy-glycoses (26,35, and 37) and the synthesis of the non-isosteric phosphonate analogue 3a of lipid X (2) are described. The 2-azido group was introduced by azidonitration. Treatment of the 1-0-acetyl-2-azido-2-deoxy-~-~-galactopyranose 22 with 1.5-3 equiv. of P(OMe), and 1.2-2.5 equiv. of TfOSiMe, gave mainly recovered starting material. In P(OMe), as the solvent, the dimethyl phosphoramidate 24 was obtained by way of a Staudinger reaction, even in the presence of TfOSiMe,. Treatment of the benzylated a-D-galacto-trichloroacetimidate 26, however, with P(OMe), and TfOSiMe, gave a 1 : I mixture of the a-and p-D-galacto-phosphondtes 27 and 28, while the acetylated a -D -g h C Oimidate 35 led to the a-D-glUC0-contigurated phosphonate 36. The stereoselectivity of the phosphonate formation is related to the relative ease of formation of oxonium-ion intermediates from 26 and 35. Starting from the phosphonate 36, deacetylation, benzylidenation, reduction of the azido group, acylation with (R)-3-(benzy1oxy)tetradecanoic acid and deprotection yielded the desired compound 3a which was crystallized in the presence of 2 equiv. of (aminomethylidyne)trimethanol (Tris). The structure of the phosphonates was deduced from their 'H-, I3C-, and ,'P-NMR spectra.

Mucin architecture behind the immune response: design, evaluation and conformational analysis of an antitumor vaccine derived from an unnatural MUC1 fragment

“…In order to improve the yield of the glycosylation reaction, as well as the anomeric ratio, we used a modification of the trichloroacetimidate method. 35 Therefore, the imidate-derivative 6 was prepared by hydrolysis of the nitro group of compound 4 ( ref. 36 ), followed by treatment with 2,2,2-trifluoro- N -phenylacetimidoyl chloride in the presence of DBU.…”

Synthesis of Glycosyl Phosphonates by Michael‐Type Addition to 2‐Nitroglycals

“…By employing different weak bases and lowering the reaction temperature, the same result was obtained. Reduction of the nitro group in compounds 2 and 3 with the use of platinized Raney nickel in ethanol yielded the corresponding amines, which were acetylated to give the known compounds 4 and 5 in 90 and 92% yield, respectively,4 as shown in Scheme . The spectroscopic data are identical to literature values 4…”

“…Vasella et al4−6 described the synthesis of such a type of nonisosteric glycosyl phosphonate analogues starting from 2‐azido‐2‐deoxy sugars, employing the trichloroacetimidate method. In continuation of our work on Michael‐type addition of various nucleophiles to 3,4,5‐tri‐ O ‐benzyl‐2‐nitroglycals,7−14 we now wish to report a convenient synthesis of such nonisosteric phosphonate analogues by Michael‐type addition of dimethyl hydrogen phosphonate to 2‐nitroglycals.…”

Direct Glycosidation of 2‐Azido‐2‐deoxyglycosyl Nitrates

“…With the general success of glycosylations with the fairly unreactive glycosyl donor 1 , we switched to investigating known 3,4,6‐tri‐ O ‐benzylated galactosyl nitrate donor 10 that was expected to be more reactive (armed) due to the less deactivating nature of the remote ethereal substituents in comparison to that of esters . Indeed, glycosyl donor 10 showed much greater reactivity than its tri‐benzoylated counterpart 1 .…”