Synthesis and characterization of heterocyclic rings linked to sugar moieties

Abstract

The aim of this work was the synthesis of several compounds namely by the regio- and stereoselective branched-chain construction starting from D-ribose or D-xylose which led to the synthesis of thio-imidate N-oxides sugar derivatives. The synthesis of compounds was made by several reactions, either starting from two different sugars or by two different lactones. Starting from D-ribose and making it react with H2SO4 in acetone, it’s easy to convert it to 2,3-O-isopropylidene-β-D-ribofuranose (1). From this compound, and by reaction with NaBH4 and NaIO4 in MeOH, 2,3-O-isopropylidene-L-erythrose (2) was obtained. The conversion into the aldoxime (3) was achieved using hydroxylamine hydrochloride in pyridine. The hydroxyl groups were protected with TBDMSCl in pyridine, giving the di- and mono-silylated compounds, respectively, compounds 4 and 5. The introduction of the SET group was achieved in a two step reaction by using NCS in DMF, and then by the addition of EtSH and Et3N, leading to the obtainment of compound 6. The de-O-silylation was performed using TBAT in THF. The ring-closing allowed the obtainment of the thioimidate N-oxide (9), and it was performed using PPh3 and DEAD in anhydre THF. The global yield of all these reactions was 42%. When starting from D-xylose, and using H2SO4 in MeOH, the primary hydroxyl group was protected, giving compound 14, in both the pyrano and furano form. The protection of the remaining hydroxyl groups was performed using NaH, BnBr and nBu4NI in DMF. The deprotection of the primary hydroxyl group was achieved by using H2SO4 and diocane, in AcOH. The oxime 17 was obtained using Na, NH2OH.HCl in MeOH, in a global yield of 35%. The lactones used were -valerolactone and D-(-)-pantolactone. When starting from the latter it wasn’t possible to obtain correspondent hydroxamic acid, but the same was not true to - valerolactone, with hydroxamic acid 7 obtained in 87%. The following steps were to protect the hydroxyl groups in this compound. However, these reactions weren’t successful. The obtained compounds were isolated and purified by column chromatography. The characterization of compounds was made by NMR analysis (1H NMR and 13C NMR). The anti oxidant activities was also evaluated, by the DPPH method, for some obtained compounds.