Stereo‐ and Regioselective Direct Multi‐Deuterium‐Labeling Methods for Sugars

Deuterium‐labeled sugars can be utilized as powerful tools for the architectural analyses of high‐sugar‐containing molecules represented by the nucleic acids and glycoproteins, and chiral building blocks for the syntheses of new drug candidates (heavy drugs) due to their potential characteristics, such as simplifying the ¹H NMR spectra and the stability of C? D bonds compared with C? H bonds. We have established a direct and efficient synthetic method of deuterated sugars from non‐labeled sugars by using the heterogeneous Ru/C‐catalyzed H–D exchange reaction in D₂O under a hydrogen atmosphere with perfect chemo‐ and stereoselectivities. The direct H–D exchange reaction can selectively proceed on carbons adjacent to the free hydroxyl groups, and the deuterium labeling of various pyranosides (such as glucose and disaccharides), as well as furanosides, represented by ribose and deoxyribose was realized. Furthermore, the desired number of deuterium atoms can be freely incorporated into selected positions by the site‐selective protection of the hydroxyl groups using acetal‐type protective groups because the deuterium exchange reaction never proceeds on positions adjacent to the protected hydroxyl groups.     

Bamford-Stevens reaction assisted synthesis of styrene C-glycosides

Modification of carbohydrates and their analogs is hindered due to multi-step synthetic methodologies involving selective protection and deprotection of multiple hydroxyl groups present in the molecule. A highly efficient route for the synthesis of 1-phenyl-2-(β-D-glycopyranosyl)ethenes has been developed from native sugars, which neither requires protection/deprotection of the hydroxyl groups nor use of any metal/metal ions. The key step of the developed methodology is the use of Bamford-Stevens reaction which led to the formation of the desired compounds in moderate to high yields in three steps only.     

Retention behavior of monosaccharides and disaccharides on titania

Summary The ability of titania to recognize the position of hydroxyl groups was previously found to result from the formation of a chelate ring between a titanium ion and the two oxygen atoms of the hydroxyl group and carboxylate anion of 2-hydroxycarboxylic acids. We investigated how titania could recognize the position of hydroxyl group of monosaccharides and disaccharides. The retention behavior of monosaccharides and disaccharides on titania was found to be characteristic. Thus, sucrose was eluted much faster than the other sugars, whereas D-ribose, D-fructose and L-sorbose were most strongly retained on titania of all of the sugars tested. It is apparent that the sugars strongly retained on titania have an axial hydroxyl group or neighboring hydroxyl groups of the same conformation.     

Semi-synthesis of neomangiferin from mangiferin

Neomangiferin, a natural xanthone derivative bearing both O- and C-glucosides, was isolated from the leaves of Gentiana asclepiadea L. and has shown potential anti-diabetic activity. We describe herein the first semi-synthesis of neomangiferin from the natural C-glucoside mangiferin and glucose. The developed synthesis presents a facile protection strategy using Jurd’s method to distinguish the different phenolic hydroxyl groups. Following this strategy, the regioselective protection of 1,3,6-hydroxyl groups was accomplished and neomangiferin was prepared by glycosylation under the phase-transfer catalysis conditions.     

糖合成中羟基的保护和去保护方法

糖中含有多个活泼的羟基.羟基的保护和去保护在有关糖的合成中具有很重要的意义.最常用的羟基保护基可归纳为三类:酯类、醚类和缩醛或缩酮类.作者对每一类中具体的羟基保护基的性质、应用作了简单综述,重点介绍了保护基的引入和脱去的方法.     

Study on the Regioselective Cleavage of Acetyl of Glycoside in Mild Condition

It is very important to selectively protect or deprotect functional groups in organic synthesis, [1] especially in sugar chemistry where many hydroxyl groups of sugars need to be protected or deprotected selectively in mild condition.     

Novel thermolabile protecting groups with higher stability at ambient temperature

Novel thermolabile hydroxyl protecting groups of increased thermostability are proposed. The stability of these groups at different temperatures ranges has been determined. The 2-pyridyl-N-(2,4-difluorobenzyl)aminoethyl unit was selected as stable at ambient temperature and very labile at increased temperature. The half-life times for the best groups were established. Application of this chemistry to the protection of different hydroxyl groups of thymidine was also demonstrated.     

The hydration of monosaccharides—an NMR study

At temperatures close to 0°C proton exchange between sugar hydroxyl groups and water is slow, and separate proton resonance peaks can be detected for the hydroxyl protons. All are shifted downfield of the water resonance, the anomeric hydroxyl proton shift being the greatest. Axial anomeric hydroxyl protons are shifted less than corresponding equatorial protons. Proton exchange with water is strongly acid and base catalyzed, but, at least in some cases, there seems to be an additional pH-independent mechanism involved. From the temperature effect on the shifts, and the effect of added dimethyl sulfoxide, we conclude that each hydroxyl group is bonded on average to two water molecules. This estimate of the hydration number for monosaccharides is far greater than those previously deduced from relaxation studies. It is suggested that the source of this difference lies in the residence times of the bound water molecules. Shifts of the hydroxyl proton resonances for sugars in methanol are compared with those for aqueous solutions and are found to be very similar. Hence it is concluded that these shifts do not reveal any special effects due to water structure. There are quite marked differences in the shifts for different sugars, and, in particular, the anomeric hydroxyl proton shifts for ketoses are smaller than those for aldoses.Taken as solvation spectra, Part 56.     

Asymmetric synthesis of the balanol heterocycle via a palladium-mediated epimerization and olefin metathesis

[formula: see text] The enantioselective formal synthesis of balanol, a potent protein kinase C inhibitor, was accomplished from D-serine utilizing a Pd-catalyzed equilibration of diastereomeric 5-vinyloxazolines to set the stereochemistry of the vicinal amino and hydroxyl groups. A ruthenium-catalyzed ring-closing metathesis was employed to form the seven-membered nitrogen heterocyle.     

DDQ mediated regiospecific protection of primary alcohol and deprotection under neutral conditions: Application of new p-methoxy benzyl-pixyl ether as reagent of choice for nucleoside protection

A simple and efficient protocol is described for regiosepecific protection of primary hydroxyl group both in nucleosides and other molecules with p-methoxy-benzyl 2,7-dimethyl pixylether (MBDPE) in presence of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Furthermore, swift deprotection of 2, 7-dimethylpixyl (DMPx) is accomplished with DDQ in MeOH. Both procedures are successfully implemented on gram-scale synthesis of modified nucleosides. This protocol offers mild and neutral conditions for selective protection and deprotection of DMPx group while compatible in presence of other conventional protecting groups such as benzoyl, benzyl, THP, TBDPS and acetonide.     

Synthesis and properties of carborane-functionalized aliphatic polyester dendrimers

The incorporation of multiple p-carborane cages within an aliphatic polyester dendrimer was accomplished through the preparation of a bifunctional carborane synthon. A p-carborane derivative having an acid and a protected alcohol functionality was found to efficiently couple to peripheral hydroxyl groups of low-generation dendrimers under standard esterification conditions. Deprotection of carborane hydroxyl groups allowed for further dendronization through a divergent approach using the highly reactive anhydride of benzylidene-protected 2,2-bis(hydroxymethyl)propanoic acid. This approach was used to prepare fourth- and fifth-generation dendrimers that contain 4, 8, and 16 carborane cages within their interior. Upon peripheral deprotection to liberate a polyhydroxylated dendrimer exterior, these structures exhibited aqueous solubility as long as a minimum of eight hydroxyl groups per carborane were present. Several of the water-soluble structures were found to exhibit a lower critical solution temperature. Additionally, irradiation of these materials with thermal neutrons resulted in emission of gamma radiation that is indicative of boron neutron capture events occurring within the carborane-containing dendrimers.     

A new oligosaccharide synthesis using special hydroxy protecting group

A new hydroxy protecting group for convenient preparation of oligosaccharide was developed using uni-chemo protection (UCP) concept. The UCP group was comprised of polymerized amino acid derivatives and protecting each hydroxyl groups by ester linkage. Depending on the polymerization degree, the hydroxyl groups were characterized and controlled. Using this protecting group, two kinds of sialyl-T analogues were successfully synthesized from same sugar parts merely by repeating Edman degradation and coupling.     

Synthesis and Fe(III)‐complexation ability of polyurethane bearing kojic acid skeleton in the main chain prepared by polyaddition of aliphatic hydroxyl groups without protection of phenolic hydroxyl groups

Polyaddition of a kojic acid dimer and diisocyanates yielded polyurethane with metal‐coordination ability owing to the phenolic hydroxyl groups of kojic acid. Although the kojic acid dimer contains two phenolic and two aliphatic hydroxyl groups, 1,5‐diazabicyclo[4.3.0]non‐5‐ene catalyzed polymerization proceeded through highly selective reactions of the aliphatic hydroxyl groups without any protection of the phenolic hydroxyl groups. The resulting polymers complexed with FeCl₃, and specific colorizations were observed. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

Synthesis and characterization ofα-butyl-ω-{3-[(2,2-dihydroxymethyl)-propionyloxy]}propylpolydimethylsiloxanes

A series of polydimethylsiloxanes containing two primary hydroxyl groups at one single chain end were synthesized by five-step reactions which included esterification, hydroxyl protection, anionic ring-opening polymerization, hydrosilylation and deprotection. The prepared compounds in each step were characterized. The results showed that each step synthesis was successfully carried out and objective products could be achieved.     

Trifluoroacetic anhydride. A convenient NMR solvent for carbohydrates. 270 MHz 1H NMR studies of 2-acetamido-2-deoxyhexoses

The use of trifluoroacetic anhydride as an NMR solvent for sugars has been explored. Dissolution of carbohydrates in this solvent is accompanied by trifluoroacetylation at the hydroxyl groups. Esterification results in downfield shifts of the sugar protons yielding very well resolved ¹H NMR spectra. The use of trifluoroacetic anhydride in the analysis of complex systems is exemplified.     

A Simple Synthesis Route for Selectively Methylated β-Cyclodextrin Using a Copper Complex Sandwich Protecting Strategy

This communication reports a novel synthesis route for the preparation of monofunctionalized β-cyclodextrin in a single stage. The approach involves only the in-situ protection of secondary hydroxyl groups as an excellent alternative to the classical procedure involving a series of five steps of protection and deprotection of hydroxyl groups (both primary and secondary ones) belonging to β-cyclodextrin.     

Nature's Strategy for Making Unusual Sugars

The deoxy sugars are an important class of carbohydrates that are derived from common sugars by the replacement of one or more hydroxyl groups with hydrogen atoms. Such a substitution generally causes a critical alteration of the biological role of the resulting sugar, and olso induces a fundamental change in the metabolic fate of the product. Particularly notable are the 3,6-dideoxyhexoses found in the lipo-polysaccharides of gram-negative bacteria and the 2,6- and 4,6-dideoxyhexoses found in many bioactive secondary metabolites. Intrigued by the great variety of the biological activities and structural features of deoxy sugars, we have undertaken an investigation into the biosynthesis of this important class of molecules. In the past few years we have focused our efforts on the formation of ascarylose, a 3,6-dideoxy sugar, and other related deoxy sugars from Yersinia pseudotuberculosis. The first part of this presentation will cover the establishment of the course of each multi-step biotransformation and the characterization of the key enzymes involved in this pathway.     

Synthesis of polyhydroxy cavitands and intramolecular inclusion of their octaester derivatives

A facile and efficient synthesis of novel cavitands containing eight hydroxyl groups was accomplished in eight steps beginning from commercially available resorcinol and the corresponding aldehydes. The synthesis combines two classical approaches to cavitand chemistry and yields the target octol cavitand molecules in gram quantities with no chromatographic separations. A variety of octaester cavitand derivatives were then prepared from the parent octols and their spectral properties are reported.     

Diphilic carbosilane dendrimers with different densities of the hydrophilic layer

A universal method for the synthesis of hydrophilic dendrimers was considered. The method is based on a combination of carbosilane dendrimers with different molecular organizations and hydrophilizing agents, viz., substituted hydride silanes containing one and three protected hydroxyl groups. The combination of a limited set of the mentioned reagents makes it possible to control the ratio of hydrophilic and hydrophobic moieties of the molecular structure in wide limits. A simple and convenient method for the removal of trimethylsilyl protection of hydroxyl groups in the surface layer of dendrimers was developed.     

Straightforward synthesis of panaxytriol: an active component of Red Ginseng

A total synthesis of (3R,9R,10R)-panaxytriol (1) was accomplished enantioselectively (40% overall yield; 30% for the longest sequence). A key step was a Cadiot-Chodkiewicz cross-coupling reaction on two fragments containing, in the aggregate, three unprotected hydroxyl groups. One fragment was synthesized by a highly enantioselective reduction of an enynone. The other arose from a highly enantioselective dihydroxylation of an allylic alcohol.