The Efficient, Enantioselective Synthesis of Aza Sugars from Amino Acids. 1. The Polyhydroxylated Pyrrolidines

Abstract

Beginning with (+)-serine or (-)-serine, as appropriate, convenient, high-yield, enantioselective synthesis of all eight stereoisomeric 2-hydroxymethyl-3,4-dihydroxypyrrolidines (the enantiomeric pairs of iminoribitol, -arabinitol, -xylitol, and -lyxitol) can be effected. The absolute configuration of the starting amino acid defines the set of azasugars produced.

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)).…”

“…Triflation of the a, b-mixture of 9 and reductive cyclization-amination by palladium catalyzed hydrogenation gave the corresponding mixture of norbonyl-like bicyclic acetal (10). Then, amino group protection, acid hydrolysis of the acetal and reduction resulted in the partially protected azasugar derivative (12). In the synthesis, the a, bmixture of 9 produced the corresponding mixture of two stereoisomers (10).…”

“…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].…”

Diastereoselective Diels-Alder reactions. The role of the catalyst

“…9 Configurationally pure substances such as 1 and the related Garner aldehyde 2 10 exemplify the utility of natural α−aminoacids for generating stereochemically defined structures suitable for incorporation into the design of synthetic targets or as agents by which asymmetry may be induced into intermediates. In this vein, we recently reported1 that Et 2 AlCl-catalyzed reaction of 1 with cyclopentadiene led to a mixture of endo diasteromeric adducts 3 and 4 in which the former, the product of α−re-face addition, predominated (88:12).…”

An Unprecedented Ring Transformation of a 4-(Aminomethyl)oxazoline Derivative to a 4-(Hydroxymethyl)imidazoline

“…Picolinic acid (3) was first coupled with methyl L-serinate 10 to give amide 4 (71%). 11 The primary alcohol was then TBS protected (92% yield of compound 5) 12 and the ester moiety reduced to again give a primary alcohol 8 (79%), which was activated with tosyl chloride and cyclized according to a literature protocol.…”