合成higher carbon sugars與phenylethanoid glycosides

Abstract

This dissertation comprises of two chapters: Chapter-I discusses the asymmetric synthesis of uncommon sugars including higher carbon and rare six carbon sugars. Higher carbon sugars are monosaccharides containing seven or more carbon atoms. Typical preparation of the higher carbon sugar involves the elongation of carbon chain and introduction of a hydroxyl group. Due to wide variation of sugar structure, there is no general synthetic strategy for high carbon sugars. The challenge stems from the variable stereochemical control when introducing of hydroxyl group. In this thesis, we have developed a strategy for asymmetric synthesis of higher carbon sugars by combination of (i) MOM Wittig homologation and (ii) proline-catalyzed a-aminoxylation. Based on this strategy, a series of L- and D-glycero heptosdies were obtained from available hexose substrates and proline catalyst. Extended application of the strategy was demonstrated in the syntehsis of rare sugars such as D-altrose, L-galactose, and L-idose. Such sugars could readily be obtained from a five-carbon sugar precursor by using the same strategy. As the stereochemical control of the proline-catalyzed aminoxylation is reagent-controlled, the stereoselectivity of introduction of hydroxyl group is fully controlled and does not suffer from a change in sugar structure and/or it’s protecting group patterns, thus enjoying a wide scope of application. Chapter-II reported a general strategy for total synthesis of a series of phenylethanoid glycosides (PhGs), namely echinacoside (1), acteoside (2), calceolarioside-A (3), calceolarioside-B (4), syringalide-B (5), and grayanoside-A (6).

The PhG compounds occur naturally and they are secondary metabolites of various flowering plants. Based on the number of glycoside residues present, these compounds are classified as monosaccharide, disaccharide, trisaccharide PhGs, etc. Nearly all of the PhG compounds contain an ester and alkene functions, and therefore hydroxyl protecting groups such as benzyl and acyl groups that commonly used in carbohydrate context are incompatible to the synthesis of the PhG compounds. As a consequence, previous synthesis of monosaccharide and disaccharide PhGs suffer from poor yield and total synthesis of trisaccharide PhG has not been reported in literature. The strategy discussed in my thesis features (i) the use of naphthylmethyl ether and silyl ether hydroxyl protecting groups; (ii) application of the low concentration glycosylation method to effect the 1,2-trans a-glycosidic bond formation; and (iii) recruitment of one-pot glycosylation method for assembly of oligosaccharide. Furthermore the antiproliferation property of the synthesized PhG compounds on prostatic cancer cell lines were also studies. The data indicated that the size of the glycoside component and the position of the cinnamic acid affect the antiproliferation capacity of the PhG compounds.

This dissertation comprises of two chapters: Chapter-I discusses the asymmetric synthesis of uncommon sugars including higher carbon and rare six carbon sugars. Higher carbon sugars are monosaccharides containing seven or more carbon atoms. Typical preparation of the higher carbon sugar involves the elongation of carbon chain and introduction of a hydroxyl group. Due to wide variation of sugar structure, there is no general synthetic strategy for high carbon sugars. The challenge stems from the variable stereochemical control when introducing of hydroxyl group. In this thesis, we have developed a strategy for asymmetric synthesis of higher carbon sugars by combination of (i) MOM Wittig homologation and (ii) proline-catalyzed a-aminoxylation. Based on this strategy, a series of L- and D-glycero heptosdies were obtained from available hexose substrates and proline catalyst. Extended application of the strategy was demonstrated in the syntehsis of rare sugars such as D-altrose, L-galactose, and L-idose. Such sugars could readily be obtained from a five-carbon sugar precursor by using the same strategy. As the stereochemical control of the proline-catalyzed aminoxylation is reagent-controlled, the stereoselectivity of introduction of hydroxyl group is fully controlled and does not suffer from a change in sugar structure and/or it’s protecting group patterns, thus enjoying a wide scope of application. Chapter-II reported a general strategy for total synthesis of a series of phenylethanoid glycosides (PhGs), namely echinacoside (1), acteoside (2), calceolarioside-A (3), calceolarioside-B (4), syringalide-B (5), and grayanoside-A (6).

The PhG compounds occur naturally and they are secondary metabolites of various flowering plants. Based on the number of glycoside residues present, these compounds are classified as monosaccharide, disaccharide, trisaccharide PhGs, etc. Nearly all of the PhG compounds contain an ester and alkene functions, and therefore hydroxyl protecting groups such as benzyl and acyl groups that commonly used in carbohydrate context are incompatible to the synthesis of the PhG compounds. As a consequence, previous synthesis of monosaccharide and disaccharide PhGs suffer from poor yield and total synthesis of trisaccharide PhG has not been reported in literature. The strategy discussed in my thesis features (i) the use of naphthylmethyl ether and silyl ether hydroxyl protecting groups; (ii) application of the low concentration glycosylation method to effect the 1,2-trans a-glycosidic bond formation; and (iii) recruitment of one-pot glycosylation method for assembly of oligosaccharide. Furthermore the antiproliferation property of the synthesized PhG compounds on prostatic cancer cell lines were also studies. The data indicated that the size of the glycoside component and the position of the cinnamic acid affect the antiproliferation capacity of the PhG compounds.