Dibutylstannylene Acetals Research Articles

Short synthetic sequence for 2-sulfation of α- l-iduronate glycosides

Hunter syndrome (mucopolysaccharidosis-II) is caused by deficiency of the lysosomal enzyme iduronate-2-sulfatase. The assay of this sulfatase requires the use of α- l-iduronate glycosides containing a sulfate at the 2-position. We report a simple, three-step procedure for the introduction of sulfate at the 2-position starting with the methyl ester of α- l-iduronate glycosides. The procedure involves protection of the 2- and 4-hydroxyl groups of the iduronate moiety as the dibutyl stannylene acetal, selective sulfation with sulfur trioxide–trimethylamine, and deprotection of the methyl ester to afford the desired 2-sulfate in 61% overall yield.

Stereoselective Synthesis of Novel Cyclic γ‐Amino Acids and Triazole Derivatives

AbstractFour polyhydroxylated γ‐azido and three γ‐amino acids 1–4 have been synthesized from (–)‐quinic acid. The nitrogen functionality in the reported derivatives was introduced through regioselective ring‐opening of cyclic sulfates with azide anion. The synthesis of the 4‐ and 5‐epimers of γ‐azido acid 1a – derivatives 2 and 3a, respectively – was achieved by regioselective oxidation of dibutylstannylene acetals derived from 1,2‐diols, followed by diastereoselective reduction of their corresponding α‐hydroxy ketones. The presence of the azide functional group in the reported γ‐azido acids was exploited to permit interlinking of bioactive molecular entities.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Semisynthesis of Long-Chain Alkyl Ether Derivatives of Sulfated Oligosaccharides via Dibutylstannylene Acetal Intermediates

Long-chain alkyl ether derivatives of sulfated oligosaccharides were semisynthesized as follows: two naturally occurring red seaweed galactans (neutral agarose and kappa-carrageenan) were submitted to partial reductive hydrolysis to give neutral and sulfated oligosaccharide alditols. The neutral disaccharide alditol (1) and its trityl ether (5) were sulfated and/or alkylated through formation of their dibutylstannylene or (bis)dibutylstannylene acetals. In these reactions, the dibutylstannylene acetals of the terminal 1,2-diols in the alditol units were more reactive than those formed on the cis-diols of the galactopyranosidic units. This property allowed the regioselective monoalkylation of a neutral tetrasaccharide alditol (2), which contained eleven free hydroxyl groups, the highest selectivity ever observed with dibutylstannylene acetals. An alkylated/sulfated derivative (11) was also obtained through the regioselective alkylation of a naturally sulfated disaccharide alditol (10, a kappa-carrageenan derivative).

Regioselective formation of 6- O-acylsucroses and 6,3′-di- O-acylsucroses via the stannylene acetal method

Regioselective formation of 6- O-acylsucroses and 6,3′-di- O-acylsucroses in one pot with good yields was achieved for the first time by a typical acylation method of sucrose via its dibutylstannylene acetal. Pure monoesters at OH-6 and diesters at OH-6,3′ obtained by these procedures were readily isolated by simple column chromatography, thus overcoming the main difficulties associated with regioselectivity, efficiency, and isolation techniques for the practical preparation. Explanations for the regioselectivities observed during this stannylene acetal-mediated reaction were also proposed based on the structures of the stannylene acetal in solution and the intramolecular migration of stannylenes.

Regioselective synthesis of long-chain ethers and their sulfates derived from methyl β- d-galactopyranoside and derivatives via dibutylstannylene acetal intermediates

A number of different conditions were investigated for the alkylation of the dibutylstannylene acetals of methyl β- d-galactopyranoside with long-chain primary alkyl bromides, decyl, dodecyl, and tetradecyl bromide. The best yields of the major products, the 3- O-alkyl ethers, were obtained by reaction of the alkyl bromide with the monodibutylstannylene acetal in DMF in the presence of cesium fluoride for extended periods of time at moderate temperatures (65 °C). These products were always accompanied by minor amounts of the 3,6-di- O-alkyl derivative. Performing the reaction with excess alkyl halide on the bis(dibutylstannylene) acetal resulted in more of the 3,6-di- O-alkyl derivative, particularly for the shorter alkyl bromides, but this product was never predominant. Sulfation of the dibutylstannylene acetal of methyl 3- O-tetradecyl-β- d-galactopyranoside resulted in the 6-sulfate in 96% yield.

Sulfatase-catalyzed assembly of regioselectively O-sulfonated p-nitrophenyl α- d-gluco- and α- d-mannopyranosides

A chemoenzymic methodology is extended to the library synthesis of regioselectively O-sulfonated pNP d-gluco and d-mannopyranosides. The method involves the sequential reactions of chemical O-sulfonation and sulfatase-catalyzed O-desulfonation. pNP 2,6-di- O-sulfo-α- d-glucopyranoside and pNP 3,6-di- O-sulfo-α- d-mannopyranoside were obtained as sodium salts using chemical methods by way of dibutylstannylene acetals or tributylstannyl ethers. They were then applied to enzyme reactions using three molluscan enzymes (snail, limpet, and abalone). The sulfatase reactions cleaved a sulfate group at the secondary O-2 or O-3 position to yield the corresponding pNP 6- O-sulfo sugars. Neither pNP 6- O-sulfo-α- d-glucopyranoside nor 6- O-sulfo-α- d-mannopyranoside became the enzyme substrate. Evidently, the molluscan sulfatases have a tendency to cleave the secondary O-sulfo group with assistance from the 6- O-sulfo group.

Determination of the configuration of ribitol in the C-polysaccharide of Streptococcus pneumoniae using a synthetic approach

The C-polysaccharide is an antigen common to all known serotypes of Streptococcus pneumoniae bacteria and is a potential target for vaccine preparation. The final uncertainty in the structure of its repeating unit, a pentasaccharide phosphate containing two phosphorylcholine side chains, has been resolved by determining the configuration of ribitol. Assignment of configuration was performed by synthesis of the two trisaccharide phosphate fragments that have either D- or L-ribitol at their centers and comparison of their 1H and 13C NMR spectral data with that of the natural polysaccharide. The syntheses employed common synthons added in different orders to an asymmetrically substituted chiral ribitol derivative to obtain opposite chiralities in the ribitol segments. The data for the trisaccharide containing D-ribitol was almost identical to that of the natural material while that for the trisaccharide containing L-ribitol differed significantly. In particular, the chemical shift differences between the two protons of the primary carbons of ribitol units directly attached to the β-2-acetamido-2-deoxy-galactopyranosyl residue were 0.10, 0.12, and 0.33 ppm, in the natural polysaccharide, the D-ribitol-containing trisaccharide, and the L-ribitol-containing trisaccharide, respectively. The average difference between the 13C NMR chemical shifts of corresponding ribitol carbons from the natural polysaccharide and the D-ribitol-containing trisaccharide phosphate was 0.034 ppm. This evidence indicates that ribitol in the C-polysaccharide has the D-configuration and that a very similar mixture of conformations in the ribitol portions is present for the natural polysaccharide and the D-ribitol-containing trisaccharide phosphate.Key words: C-polysaccharide, Streptococcus pneumoniae, ribitol, dibutylstannylene acetal, determination of configuration.

Determination of the configuration of ribitol in the C-polysaccharide of <i>Streptococcus pneumoniae</i> using a synthetic approach

The C-polysaccharide is an antigen common to all known serotypes of Streptococcus pneumoniae bacteria and is a potential target for vaccine preparation. The final uncertainty in the structure of its repeating unit, a pentasaccharide phosphate containing two phosphorylcholine side chains, has been resolved by determining the configuration of ribitol. Assignment of configuration was performed by synthesis of the two trisaccharide phosphate fragments that have either D- or L-ribitol at their centers and comparison of their 1H and 13C NMR spectral data with that of the natural polysaccharide. The syntheses employed common synthons added in different orders to an asymmetrically substituted chiral ribitol derivative to obtain opposite chiralities in the ribitol segments. The data for the trisaccharide containing D-ribitol was almost identical to that of the natural material while that for the trisaccharide containing L-ribitol differed significantly. In particular, the chemical shift differences between the two protons of the primary carbons of ribitol units directly attached to the β-2-acetamido-2-deoxy-galactopyranosyl residue were 0.10, 0.12, and 0.33 ppm, in the natural polysaccharide, the D-ribitol-containing trisaccharide, and the L-ribitol-containing trisaccharide, respectively. The average difference between the 13C NMR chemical shifts of corresponding ribitol carbons from the natural polysaccharide and the D-ribitol-containing trisaccharide phosphate was 0.034 ppm. This evidence indicates that ribitol in the C-polysaccharide has the D-configuration and that a very similar mixture of conformations in the ribitol portions is present for the natural polysaccharide and the D-ribitol-containing trisaccharide phosphate.Key words: C-polysaccharide, Streptococcus pneumoniae, ribitol, dibutylstannylene acetal, determination of configuration.

Synthetic Studies on Selectin Ligands/Inhibitors: Synthesis and Biological Activity of the Sulfated and Phosphorylated Multivalent β-D-Galactopyranosides Containing Fatty Alkyl Residues1 2

Ten sulfated and three phosphorylated β-D-galactopyranoside dimers and one sulfated β-D-galactopyranoside trimer containing fatty alkyl residues in place of ceramide have been synthesized. The coupling of 2,3,4,6-tetra-O-acetyl-α-D-galactopyranosyl bromide (2) with branched fatty alkyl diols and a triol (1a-1j) using mercury bromide as an activating agent gave the corresponding parent glycolipids (4a-4j) in good yields. Regioselective sulfation of these parent glycolipids through the dibutylstannylene acetals produced the target sulfated glycolipids, 3-sulfate (5a-5j) while stepwise phosphorylation with dibenzyloxy(diisopropylamino) phosphine gave the phosphorylated glycolipids, 3,4-bisphosphate (9e, g, i). The synthetic glycolipids were assayed for their ability to block the adhesion of HL-60 cells to immobilized P-, L- and E-selectin. 1. Dedicated to the memory of Professor Akira Hasagawa. 2. Synthetic studies on sialoglycoconjugates, Part 102. For Part 101, see Y. Makimura, H. Ishida, A. Kondo, A. Hasegawa and M. Kiso, J. Carbohydr. Chem., in press.

Synthetic Studies on Selectin Ligands/Inhibitors: One-Pot Synthesis of the Mono- and Oligo-Sulfated 2-(Tetradecyl)Hexadecyl β-D-Galacto- and Lactopyranosides as the Sulfatide Mimetics1

Regioselective sulfation through the dibutylstannylene acetals was applied to the key step to prepare a number of sulfated saccharides which are active as the inhibitors of L- and P-selectin. The number and the positions of the sulfate groups were confirmed by NMR and MS analyses. Using this methodology, our target sulfated glycolipids (6-9, 12-14) were conveniently synthesized in one-pot from free 2-(tetradecyl)hexadecyl β-D-galactopyranoside 5 and lactoside 11. 1. Synthetic studies on sialoglycoconjugates, Part 97. For Part 96, see E. Tanahashi, K. Murase, M. Shibuya, Y. Igarashi, H. Ishida, A. Hasegawa and M. Kiso, J. Carbohydr. Chem., previous paper this issue.

Organotin-Mediated Monoacylation of Diols with Reversed Chemoselectivity. Mechanism and Selectivity1

The monoesterification of unsymmetrically substituted diols, which occurs at the most substituted hydroxyl when activation of the substrate is achieved through its dibutylstannylene acetal, has been investigated to ascertain the origin of the unusual reversal of chemoselectivity. A mechanism in which the dibutylstannylene acetal plays the double role of reagent and catalyst has been established, which accounts for the reactivity, selectivity, and product distribution of the reaction. The reaction pathway involves three subsequent steps, namely, (a) esterification, (b) intra- and intermolecular transesterification, and (c) quench; interplay between kinetic and thermodynamic control over the three steps is responsible for the observed product distribution. The knowledge of the reaction mechanism allows for adjustment of experimental conditions to achieve optimum selectivity, which can be >99% with the appropriate choice of reagents. The stannylation procedure converts hydroxyls into functional groups highly...

ChemInform Abstract: Microwave Accelerated Organic Transformations: Dibutylstannylene Acetal Mediated Selective Acylation of Polyols and Amino Alcohols Using Catalytic Amounts of Dibutyltin Oxide. Influence of the Solvent and the Power Output on the Selectivity.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Microwave Accelerated Organic Transformations: Dibutylstannylene Acetal Mediated Selective Acylation of Polyols and Amino Alcohols using Catalytic Amounts of Dibutyltin Oxide. Influence of the Solvent and the Power Output on the Selectivity

Microwave Accelerated Organic Transformations: Dibutylstannylene Acetal Mediated Selective Acylation of Polyols and Amino Alcohols using Catalytic Amounts of Dibutyltin Oxide. Influence of the Solvent and the Power Output on the Selectivity

Control of regioselectivity in reactions of dialkylstannylene acetals. Part I. A dramatic reversal of regioselectivity in mono-p-toluenesulfonation reactions

The regioselectivities of p-toluenesulfonation reactions of dialkylstannylene acetals obtained from a number of carbohydrate-derived terminal 1,2-diols in the absence of added nucleophiles have been explored as functions of the carbohydrate structure, the nature of the alkyl group on tin, the solvent, and the reaction temperature. Virtually all dibutylstannylene acetals react preferentially on the primary oxygen atom, sometimes with excellent regioselectivity. Increasing the steric bulk of the alkyl substituents on tin increases the preference for reaction at the secondary oxygen atom, but at the expense of increased reaction times. Hexamethylenestannylene acetals react at about the same rate as dibutylstannylene acetals; in almost all cases, they react preferentially on the secondary oxygen atom, sometimes with excellent regioselectivity.

Regioselective sulfation of disaccharides using dibutylstannylene acetals

Regioselective sulfation of partially protected disaccharides was achieved from their dibutylstannylene acetals by treatment with sulfur trioxide/trimethylamine. Using this methodology 3′-sulfo-N-acetyllactosaminide 5, which is a substrate for fucosyltransferases and is the partial structure of 3′-sulfo-Lewis x, can be synthesised in two steps from the N-acetylglucosaminide 3 without the need for hydroxyl group protection. Regioselective sulfation was also observed for partially protected maltosides 6 and 7.

ChemInform Abstract: Rapid Formation of Dibutylstannylene Acetals from Polyhydroxylated Compounds Under Microwave Heating. Application to the Regioselective Protection of Polyols and to a Catalytic Tin‐Mediated Benzoylation.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Regioselective Formation of Di-O-Benzyl-Substituted Hexopyranosides via Stannylene Acetal Intermediates

Abstract The reactions of dibutylstannylene acetals derived from several methyl hexopyranosides with benzyl bromide have been investigated. These reactions occur readily in benzyl bromide at 85 °C. At reaction times of one to two days, the major products are di-O-benzyl derivatives. In several cases, single di-O-benzyl derivatives are the predominant products: methyl α-D-glucopyranoside and methyl β-D-galactopyranoside gave the 2,6- and 3,6-di-O-benzyl ethers in 82 and 70% yields, respectively. The species present in these reactions and the reaction pathway are discussed.

Rapid Formation of Dibutylstannylene Acetals from Polyhydroxylated Compounds under Microwave Heating. Application to the Regioselective Protection of Polyols and to a Catalytic Tin-mediated Benzoylation

The formation of dibutylstannylene acetals from polyols and dibutyltin oxide is accelerated under microwave heating. The method is applied to the regioselective benzoylation of a variety of polyols. Some preliminary results on a catalytic tin-mediated benzoylation of polyols are also presented.

The regioselective tert-butyldimenthylsilylation of the 6′-hydroxyl group of lactose derivatives via their dibutylstannylene acetals

The regioselective tert-butyldimenthylsilylation of the 6′-hydroxyl group of lactose derivatives via their dibutylstannylene acetals

An Improved Method for the Regioselective Oxidation of Stannylene Acetals and Dimerization of the α-Hydroxyketone Products

Abstract Dibutylstannylene acetals, particularly those derived from terminal diols, were found to be oxidized regiospeeifically to α-hydroxyketones in good to excellent yield by N-bromosuccinimide. One of the products, 3-deoxy-l,2-O-isopropylidene-α-D-erythro hexofuranos-5-ulose (8), exists to about 20% in solution as a mixture of dimers. One of the dimers can be obtained as a solid and its structure was determined tentatively by a combination of NMR experiments and MM3 molecular mechanics calculations.