Study On The Design And Synthesis Of Analogues Of Astragalines

Astragalines are new skeleton pyrrole alkaloids with a strong anti-ageing activity newly found in Astragalus. Eight amino sugar derivatives.Nine Astragaline analogues of novel N-carbohydrate-derived heterocyclic compounds and five Astragaline analogues of N-(methoxybenzyl) pyrroles were designed and synthesized (of which twelve are new compounds). The preliminary structures of Astragalines with absolute configuration were inferred by comparison of NMR data with Capparisine and Acortatarins which had the same skeleton and determined absolute configuration reported recently.In the course of the synthesis of these compounds, the reactions of carbohydrates, such as Amadori reaction, isopropylidene formation reactions, hydro-debenzylations, Paal-Knorr pyrrole synthesis, Clauson-Kaas reactions, oxidations, reductive amination reaction, oxime formation and hydrogenation reactions, reduction of oxime oxime with nickel alloy, Mitsunobu reactions, chloronation, bromonation, iodination, formation of toluenesulfonate, synthesis of imidazole-1-sulfonates, selective cleavage of isopropylidene, oxidation of 1,2-dihydroxy compound, VHA reaction, Gabrial reaction, SN2 reaction of sodium of pyrroles with Ts-ester, SN2 reactions of imidazole-1-sulfonates with sodium of heterocyclic compounds, selective acetylation, deiodination with sodium hydride, et al. were studied carefully. A lot of attention was paid to the three-dimensional configurations of reaction products by means of NMR, X-ray diffraction and other methods. These established the basis of methodologies for the synthesis of Astragalines and their analogues.Three new single crystals, -[bis(phenylmethyl)amino]-1-deoxy-4,5-O-isopropylidene-β-D-fructopyranose,2,3:4,5-Di-O- isopropylidene -β-D-fructos-1-yl1 p-toluenesulfonate and 1-(1H-pyrrole-1-y1)-1-deoxy-2,3:4,5-Di-O-isopropylidene -β-D-fructopyranose, were prepared and their crystal structures were determined. forty related compounds were characterized by spectrals. Specific rotations of twenty-two compounds were detected.The first nucleophilic substitution reaction of imidazole-1-sulfonates with pyrroles and other nitrogen heterocyclic compounds was developed. A class of novel N-carbohydrate-derived heterocyclic compounds are prepared by this displacement reaction. The desired carbon-nitrogen bond formation proceeds under mild conditions to generate the coupling products in good yields with readily available and inexpensive reagents. This method is particularly suitable for carbohydrate imidazole-1-sulfonates of primary alcohols.