Stereoselective Syntheses of 1,4-Dideoxy-1,4-imino-octitols and Novel Tetrahydroxyindolizidines

Abstract

A new route for the preparation of four new indolizidines, (1R,2S,6S,7S,8aS)- and (1R,2S,6R,7R,8aS)-1,2,6,7-tetrahydroxyindolizidine (30 and 32) and (1S,2R,7S,8S,8aR)- and (1S,2R,7R,8R,8aR)-1,2,7,8-tetrahydroxyindolizidine (44 and 46), is reported. The synthesis is based on Knoevenagel homologation of the readily available enantiomerically pure pyrrolidin-carbaldehydes 13 and 37followed by asymmetric dihydroxylation of the subsequent alkenyl pyrrolidines and cyclization of the corresponding imino-octitols. The new indolizidines and their precursors (imino-octitols 20, 25, 26) and indolizidinones 28a and 28b have been tested for inhibitory activities toward 26 glycosidases. The enzymatic inhibition of trans-7-hydroxy-d-(-)-swainsonine (44) toward alpha-mannosidases is similar to that described for trans-7-hydroxy-l-(+)-swainsonine (11b) toward naringinase (alpha-l-rhamnosidase from Penicillium decumbens).

Synthesis of Acryclic Acid Ethyl Ester from Aldehydes Catalyzed by Copper Triflates

“…Moreover, half-esters of malonates are as inexpensive as the corresponding phosphorous based reagents and can also be obtained from inexpensive dialkylmalonates. In addition, by this method (E) vs (Z) selectivity varies and, most importantly, in the reaction with enolizable aldehydes, not α, β-unsaturated esters (or their mixtures) are commonly obtained [4]. In this context Benjamin et.…”

A practical and efficient synthesis of five-membered azasugar derivatives

“…The conventional methods for constructing an azasugar ring includes: intramolecular substituted aminationcyclizatioN [14][15][16][17][18][19], intramolecular amination-cyclization of aminosugar derivatives [20,21], reductive aminationcyclization of dicarbonyl compounds [22,23], metathesis [24,25], cycloaddition [26,27] and so on. The key step to construct the azasugar ring is the stereospecific cyclization [8][9][10][11][12][13][14][15][16][17][18][19][20][21]. In addition, Fleet and coworkers [28,29] reported a synthesis of 5-membered azasugars via the key intermediate of norbonyl like bicyclic acetal, (Scheme 1, route (a)).…”

“…Because the glycosidases can adjust the biosynthesis and hydrolysis of the glucoproteins which play important roles in biological recognition and structure modulation of enzymes, such kind of enzyme inhibitors are potential therapeutic reagents for the treatment of diseases caused by disorders of carbohydrate metabolism such as those used for anti-diabetic, antiviral (including AIDS), antibiotics and anticancer agents [1][2][3][4][5][6][7]. The important biological activity of azasugars and their excellent potentia, on pharmaceutical applications has attracted great attention for the research on their synthesis, biological activipy and application, which has got remarkable progress [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19].…”

The Structure, Biological Activities and Synthesis of 3- Hydroxylpyrrolizidine Alkaloids and Related Compounds

“…Robina et al reported a stereoselective route to novel tetrahydroxyindolizidines in which a tetrahydroxy-pyrrolizidine 83 was formed as a side-product (Scheme 1.7) [46,47]. The pyrrolidine 81 was cyclized to a mixture of the indolizidine 82 and the pyrrolizidine 83 in 69% and 28% yield, respectively, by sequential treatment with aqueous TFA and then aqueous ammonia.…”