Waldemar Pfrengle

Carbohydrates as chiral templates: asymmetric ugi-synthesis of alpha-amino acids using galactosylamines as the chiral matrices

Abstract In the presence of Lewis acid catalysts O-acetyl- (1) and O-pivaloyl- (2) protected β-D-galactopyranosylamines react with aldehydes, isocyanides and carboxylic acids in Ugi-four-component-condensations to give the corresponding N-galactosyl-amino acid amide derivatives 3,5 in almost quantitative yields. Zinc chloride is the most effective Lewis acid catalyst. At 0°C or even at room temperature the (2R,β-D)-diastereomers of the amino acid derivatives 3,5 are formed with high diastereoselectivity. If the sterically more demanding O-pivaloyl galactosylamine 2 is used at -78°C to -25°C the stereoselectivity often exeeds 20:1 favouring the (2R,β-D) diastereomers 5. After one recrystallisation pure (R)-amino acid derivatives 5 are obtained in yields of 80–95%. In addition to the high yields and stereoselectivity the amino acid synthesis discribed here has the further advantage that it neither requires organometallic reagents and intermediates nor exclusion of oxygen and moisture. Two step acid hydrolysis of the N-galactosylamino acid amide derivatives 5 delivers the enantiomerically pure (R)-amino-acids 8 in high yields.

Reversal of asymmetric induction in stereoselective Strecker synthesis on galactosyl amine as the chiral matrix

Abstract The reversal of the direction of asymmetric induction in Lewis acid catalyzed Strecker synthesis using the 2,3,4,6-tetra-O-pivaloyl-β-D-galactopyranosyl amine 1 is described. In isopropanol or tetrahydrofuran 1 had given ( R )-diastereomers of the corresponding α-amino nitriles preferably. However, in chloroform in the presence of heterogeneous zinc chloride the same auxiliary alternatively leads to an excess of the ( S )-diastereomers.

Carbohydrates as chiral templates: Diastereoselective Ugi synthesis of (S)-amino acids using O-acylated D-arabinopyranosylamine as the auxiliary

Abstract Enantiomerically pure (S)-amino acids are synthesized via a highly diastereoselective Ugi reaction using 2,3,4-tri-O-pivaloyl-α-D-arabinopyranosylamine as the chiral template.

Regioselective Glycosylation of Glucosamine and Galactosamine Derivates Using O-Pivaloyl Galactosyl Donors

Penta-O-pivaloyl-galactopyranose and tetra-O-pivaloyl-galactopyranosyl bromide after electrophilic activation reacted with 6-O-protected 2-azido-galactosides to give the precursor structures of the Thomsen-Friedenreich antigen disaccharide with high regioselectivity, but low yield.With 4,6-Obenzylidene protected 2-azidogalactosides and 2-O-pivaloyl phenylthio galactosides, T-antigen disaccharides of this type were obtained in good yields. Glycosylation reactions of 4,6-O-benzylidene protected glucosamine derivatives with O-pivaloyl protected galactosyl bromide efficiently gave lactolactosamine disaccharides. Even a thioglycoside was efficiently galactosylated by this method resulting in the formation of a disaccharide thioglycoside useful itself as a potential glycosyl donor.

Effective 1,2-trans-glycosylation of complex alcohols and phenols using the oximate orthoester of O-pivaloyl glucopyranose

The highly stereoselective β-glycosylation of the complex steroid alcohols (2b)–(2d), the steroid phenol (2e), and the serine derivative (2f) is achieved in high yields using the new glycosyl donor 1,2-O-(1-N-1-phenylethylideneamino-oxy)-2,2-dimethylpropylidene-3,4,6-tri-O-pivaloyl-α-D-glucopyranose (1) in the presence of boron trifluoride–diethyl ether.