Synthesis of 2,4-dideoxy-4-hydroxyphosphonoyl-D-erythro- and -L-threo-pentofuranoses

Abstract

Treatment of 3,5, 6-trideoxy-1,2-O-isopropylidene-6-nitro-α-D-erythro-hex-5-enofuranose with dimethyl phosphonate in the presence of triethylamine, followed by catalytic hydrogenation and then deamination with nitrous acid, provided mainly a 2 : 1 mixture of 3,5-dideoxy-5-dimethoxy-phosphinoyl-1,2-O-isopropylidene-α-D-ribo- and -β-L-lyxo-hexofuranose in 57% overall yield. This mixture was deacetonated, oxidized with sodium periodate, and then treated with acidic methanol to afford methyl 2,4-dideoxy-4-dimethoxyphosphinoyl-α,β-D-eythro-pentopyranosides (41% overall yield from the aforementioned phosphinoylfuranose) and -L-threo-pentopyranosides (17% overall yield). The major products were reduced with sodium dihydrobis-(2-methoxyethoxy)-aluminate, followed by hydrolysis with acid and then oxidation with hydrogen peroxide, to afford the title D-erythro compounds, whereas similar treatment of the minor pyranosides afforded the corresponding L-threo-pentofuranoses. These compounds were converted into the corresponding 1,3,5-tri-O-acetyl-5-methoxyphosphonoyl derivatives, whose structures and conformations [mostly ³T₂(D) for one and ²T₃(L) for the other] were established by spectroscopy.