Synthesis of 4-cyano and 4-nitrophenyl 1,6-dithio- d-manno-, l-ido- and d-glucoseptanosides possessing antithrombotic activity

Abstract

1,6-Anhydro-3,4- O-isopropylidene-1-thio- d-mannitol was converted into its sulfoxide which after hydrolysis, acetylation and subsequent Pummerer rearrangement gave the penta- O-acetyl-1-thio- d-mannoseptanose anomers in excellent yield. This anomeric mixture was used as donor for the glycosylation of 4-nitro- and 4-cyanobenzenethiol in the presence of boron trifluoride etherate and trimethylsilyl triflate, respectively, to yield the corresponding thioseptanosides in high yield. The same strategy was applied for the synthesis of the corresponding l-idothioseptanosides using 1,6-anhydro-3,4- O-isopropylidene-1-thio- l-iditol as starting material. The penta- O-acetyl- d-glucothioseptanose donors could not be synthesised the same way, as the Pummerer reaction of the corresponding tetra- O-acetyl-1,6-thioanhydro-1-thio- d-glucitol sulfoxides led to an inseparable mixture of the corresponding l-gulo- and d-glucothioseptanose anomers. Therefore, d-glucose diethyl dithioacetal was converted via its 2,3,4,5-tetra- O-acetyl-6- S-acetyl derivative into an anomeric mixture of its 6-thio-septanose and -furanose peracetates which could be separated by column chromatography. Condensation of the 6-thio-glucoseptanose peracetates with 4-cyano- and 4-nitrobenezenethiol in the presence of boron trifluoride etherate afforded anomeric mixtures of the corresponding thioseptanosides. The d-manno-, l-ido- and d-glucothioseptanosides obtained after Zemplén deacetylation of these mixtures were tested for their oral antithrombotic activity.