Inge Lundt

Chemically methylated and reduced pectins: preparation, characterisation by 1H NMR spectroscopy, enzymatic degradation, and gelling properties

The gelling properties of pectins are known to be closely related to the degree of methylation (DM) and the distribution of the ester groups. In order to investigate this dependency, a natural citrus pectin (DM 64%) has been methylated to pectins with higher DM or saponified to achieve pectins with lower DM. A simple method for determination of DM by 1H NMR spectroscopy is presented. New modified pectins have been prepared by treatment of pectins having different DM with NaBH(4) to reduce selectively the methyl esters to primary alcohols in the presence of free acids. The degree of reduction (DR) and the DM of the remaining carboxylic acids could likewise be determined by 1H NMR spectroscopy. The new reduced pectins are recognized by the pectin degrading enzymes polygalacturonase PGI and PGII as well as by pectin lyase, all from Aspergillus niger, but the enzymes exhibit lower specific activities as compared with unmodified pectin. The new reduced pectins exhibit high gelling properties.

Preparation of some bromodeoxyaldonic acids

Abstract Reaction of L -ascorbic acid with hydrogen bromide in acetic acid gave 6-bromo-6-deoxy- L -ascorbic acid, which was converted into 5,6-dideoxy- D - glycero -hex-2,3-enono-1,4-lactone. Hexonic acids or their lactones also gave bromo compounds on treatment with HBrAcOH. From D -galactono-1,4-lactone a 6-bromo derivative was obtained. Calcium D -gluconate yielded 2,6-dibromo-2,6-dideoxy- D -mannono-1,4-lactone, whereas D -mannono-1,4-lactone gave 2,6-dibromo-2,6-dideoxy- D -glucono-1,4-lactone.

Two isosteric fluorinated derivatives of the powerful glucosidase inhibitors, 1-deoxynojirimycin and 2,5-dideoxy-2,5-imino-d-mannitol: Syntheses and glucosidase-inhibitory activities of 1,2,5-trideoxy-2-fluoro-1,5-imino-d-glucitol and of 1,2,5-trideoxy-1-fluoro-2,5-imino-d-mannitol

Abstract 1,2,5-Trideoxy-2-fluoro-1,5-imino- d -glucitol, the 2-deoxyfluoro derivative of 1-deoxynojirimycin, as well as 1,2,5-trideoxy-1-fluoro-2,5-imino- d -mannitol and 2,5-dideoxy-2,5-imino-1- O -methyl-d-mannitol, two new analogues of the natural product and powerful glucosidase inhibitor 2,5-dideoxy-2,5-imino- d -mannitol, were synthesised featuring glucose isomerase-catalysed aldose-ketose interconversion reactions as the key steps of the syntheses. Results of inhibition studies conducted with these compounds and previously obtained deoxyfluoro derivatives of 1-deoxynojirimycin, employing glucosidases from various sources, showed that the replacement of a hydroxyl function by fluorine caused an impairment of the inhibitory potency. This effect was smallest for the hydroxyl group at C-6 up to four orders of magnitude larger for replacements at C-2 and C-3. Title compounds were synthesized by chemical and chemo-enzymatic routes.

Syntheses of sugar-related trihydroxyazepanes from simple carbohydrates and their activities as reversible glycosidase inhibitors.

Five diastereomeric trideoxy-1,6-iminohexitols were synthesised, and their inhibitory activities were determined against selected glycosidases. For comparison, 1,4,5-trideoxy-1,5-imino-D-lyxo-hexitol, the 4-deoxy derivative of 1-deoxymannojirimicin, was prepared by enzymatic isomerisation of 6-azido-3,6-dideoxy-D-ribo-hexose into the corresponding 2-ulose and subsequent hydrogenation accompanied by intramolecular reductive amination.

1,5-Anhydro-D-fructose; a versatile chiral building block: biochemistry and chemistry.

There is a steadily increasing need to expand sustainable resources, and carbohydrates are anticipated to play an important role in this respect, both for bulk and fine chemical preparation. The enzyme alpha-(1-->4)-glucan lyase degrades starch to 1,5-anhydro-D-fructose. This compound, which has three different functional properties, a prochiral center together with a permanent pyran ring, renders it a potential chiral building block for the synthesis of valuable and potentially biologically active compounds. 1,5-Anhydro-D-fructose is found in natural materials as a degradation product of alpha-(1-->4)-glucans. The occurrence of lyases and the metabolism of 1,5-anhydro-D-fructose are reviewed in the biological part of this article. In the chemical part, the elucidated structure of 1,5-anhydro-D-fructose will be presented together with simple stereoselective conversions into hydroxy/amino 1,5-anhydro hexitols and a nojirimycin analogue. Synthesis of 6-O-acylated derivatives of 1,5-anhydro-D-fructose substituted with long fatty acid residues is carried out using commercially available enzymes. Those reactions lead to compounds with potential emulsifying properties. The use of protected derivatives of 1,5-anhydro-D-fructose for the synthesis of natural products is likewise reviewed. The potential utilization of this chemical building block is far from being exhausted. Since 1,5-anhydro-D-fructose now is accessible in larger amounts through a simple-enzyme catalyzed degradation of starch by alpha-(1-->4)-glucan lyase, the application of 1,5-anhydro-D-fructose may be considered a valuable contribution to the utilization of carbohydrates as the most abundant resource of sustainable raw materials.

Deoxyiminoalditols from aldonolactones--V. Preparation of the four stereoisomers of 1,5-dideoxy-1,5-iminopentitols. Evaluation of these iminopentitols and three 1,5-dideoxy-1,5-iminoheptitols as glycosidase inhibitors.

The four stereoisomeric 1,5-dideoxy-1,5-iminopentitols with D-arabino-(D-lyxo-) (3), ribo- (9), L-lyxo (L-arabino-) (13) and xylo-(18) configurations were synthesized. The corresponding aldonolactones (1, 7 and 11) or aldonic acid ester (15b) having a leaving group at C-5 gave by reaction with aqueous ammonia, the 5-amino-5-deoxy-1,5-lactams, 2, 8, 12 and 17, respectively. Reduction of the lactam function using sodium borohydride/acetic or trifluoroacetic acid, or borane dimethyl sulfide complex yielded the iminopentitols. The compounds 3, 9, 13 and 18, together with the three 1,5-dideoxy-1,5-iminoheptitols 19,20 and 21 were tested for inhibition of the glycosidase activities present in an extract from human liver. Compound 18 was a potent and 19 a moderately good inhibitor of beta-glucosidase. Compound 3 together with 19, 20 and 21, all having D-arabino-configuration at the hydroxy-substituted carbon atoms, were good inhibitors of alpha-L-fucosidase.

The preparation of some bromodeoxy- and deoxy-hexoses from bromodeoxyaldonic acids☆

Abstract The reduction of 2,6-dibromo-2,6-dideoxy- D -mannono- and 2,6-dibromo-2,6-dideoxy- D -glucono-1,4-lactone with sodium borohydride affords 2,6-dibromo-2,6-dideoxy- D -mannose and 2,6-dibromo-2,6-dideoxy- D -glucose, respectively, which may be isolated as their acetates. Similarly, 2-bromo-2,6-dideoxy- L- -glucono-1,4-lactone yields 2-bromo-2,6-dideoxy- L -glucose. Hydrogenolysis of 2,6-dibromo-2,6-dideoxy- D -mannono-1,4-lactone gives 6-bromo-2,6-dideoxy- D - arabino -hexono-1,4-lactone and, subsequently, 2,6-dideoxy- D - arabino -hexono-1,4-lactone. Reduction of the latter with bis(1,2-dimethylpropyl)borane leads to 2,6-dideoxy- D - arabino -hexose, which may be converted into methyl 2,6-dideoxy-3,4-di- O - p -nitrobenzoyl- D - arabino -hexopyranoside.

Deoxyiminoalditols from aldonolactones. III: Preparation of 1,4-dideoxy-1,4-imino-L-gulitol. -Evaluation of 1,4-dideoxy-1,4-iminohexitols as glycosidase inhibitors

Abstract 2,6-Dibromo-2,6-dideoxy-D-altrono-1,4-lactone ( 1 ) was converted into a mixture of 2,3-anhydro-6-bromo-6-deoxy-D-allono-1,4- ( 7 ) and -1,5-lactone ( 8 ), which by treatment with aqueous NH 3 (25%) gave 3,6-dideoxy-3,6-imino-D-gluconic acid ( 9 ). Convertion into the 1,4-lactone 10 followed by reduction with NaBH 4 gave 1,4-dideoxy-1,4-imino-L-gulitol ( 11 ). - Reduction of the dibromolactone 1 gave 2,6-dibromo-2,6-dideoxy-D-altritol (1,5-dibromo-1,5-dideoxy-D-talitol) ( 2 ) which was unstable since it was readily transformed into 3,6-anhydro-2-bromo-2-deoxy-D-altritol ( 3 ). Treatment of either 2 or 3 with aqueous NH 3 (25%) gave 1-amino-1-deoxy-3,6-anhydro-D-allitol ( 6 ). - The reaction of the bromo compounds with aqueous NH 3 were followed by 13 C NMR spectroscopy. - Evaluation of nine 1,4-dideoxy-1,4-iminohexitols with D- and L- allo , talo -, galacto -, ido - and with L- gulo -configurations as glycosidase inhibitors is reported.

2-bromo-2-deoxy sugars as starting materials for the synthesis of α- or β-glycosides of 2-deoxy sugars

Abstract 3,4-di- O -acetyl-2,6-dibromo-2,6-dideoxy-α- d -gluco- ( 1 ) and - d -manno-pyranosyl bromide ( 18 ) gave, in glycosidation reactions, 1,2- trans -glycosides. β- d -Glycosides were formed as the main products from 1 in moderate yields, whereas 18 gave α- d -glycosides exclusively and in high yields. The 2,6-dibromo-2,6-dideoxy-β- d -glucosides were converted into the 2,6-dideoxy-β- d -glycosides by treatment with tributylstannane, and removal of the bromine atoms from 2,6-dibromo-2,6-dideoxy-α- d -mannosides to give 2,6-dideoxy-α- d -glycosides could also be effected by catalytic hydrogenolysis.

Simple synthesis of (R)-Carnitine from d-Galactono-1,4-lactone

Abstract (R)-Carnitine was prepared by two simple, short and efficient syntheses starting from ld -galactono-1,4-lactone.