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

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‐ O ‐acetyl‐2‐azido‐2‐deoxy‐β‐D‐galactopyranose 22 with 1.5‐3 equiv. of P(OMe) 3 and 1.2‐2.5 equiv. of TfOSiMe 3 gave mainly recovered starting material. In P(OMe) 3 as the solvent, the dimethyl phosphoramidate 24 was obtained by way of a Staudinger reaction, even in the presence of TfOSiMe 3 . Treatment of the benzylated α‐D‐ galacto ‐trichloroacetimidate 26 , however, with P(OMe) 3 and TfOSiMe 3 gave a 1:1 mixture of the α‐ and β‐D‐ galacto ‐phosphonates 27 and 28 , while the acetylated α‐D‐ gluco ‐ imidate 35 led to the α‐D‐ gluco ‐configurated 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‐(benzyloxy)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 1 H‐, 13 C‐, and 31 P‐NMR spectra.