Alkyl Orthoacetates Research Articles

Crystal structure of methyl-3, 4-O-ethylidene-β-L- arabinopyranoside

The acid-catalyzed ethylidenation of several methyl pentopyranosides has been studied and syntheses of many cyclic alkyl orthoacetates from pentopyranosides have been reported. In a study of the scope and limitation of the reduction of sugar epoxides with diborane/sodium borohydride, methyl-4-O-acetyl-2,3-anhydro-β-L-lyxopyranoside was reduced, yielding two products: methyl-2,3-anhydro-β-L-lyxopyranoside and methyl-3,4-O-ethylidene-β-L-arabinopyranoside. The latter product was characterized by X-ray diffraction and its structure indicates that the epoxide was not reduced as expected; rather, the epoxide was opened by the hydroxyl group of the reduced acetyl. Crystals of the title compound are monoclinic, space group P21 with the following cell dimensions: a = 5.818(l) A, b = 10.842(2) A, c =7.251(1) A, β = 91.47(1)°, Z = 2. Complete three-dimensional data (2θmax = 150° for Cu Kα) were collected on a CAD-4 diffractometer by the ω−2θ scan method. The structure was solved by the application of direct methods and refined by full-matrix least-square methods to a final reliability index of 0.04 for the observed 1031 reflections (I ≥ 3σ). The ethylidene ring has a twist conformation with a torsion angle of −42.8° about the C4–O bond. The pyranose ring is in a flattened chair conformation with the C2–C3–C4–C5 torsion angle of 33.5°. Of the acetal bond lengths, the C5–O5 length, (1.423 A) is shorter than the values found in other methyl pyranosides. O2–H is involved in a bifurcated hydrogen bond intramolecularly to O1 and intermolecularly to O4.

Development of a drug delivery system for the treatment of periodontal disease based on bioerodible poly(ortho esters)

Poly(ortho esters) prepared by the condensation of 1,2,6-hexanetriol and an alkyl orthoacetate are viscous, semisolid materials at room temperature that can be injected using a blunt needle. When tetracycline was incorporated into these materials, complete release occurred within about 24 hours, but when small amounts of Mg(OH) 2 were incorporated into the polymer release could be extended to many weeks, and a loading of 0.5wt% resulted in sustained release of about 10 days. When adhesion was tested using bovine teeth, cohesive failure of the pure polymer occurred at a force of about 392 mNcm −2 and cohesive failure of a polymer incorporating 10wt% tetracycline and 1 wt% (Mg(OH) 2 occurred at about 118 mNcm −2. The combination of injectability, dentoadhesiveness and ability to control accurately the release of incorporated antibiotics makes these materials promising candidates for bioerodible delivery systems useful in the treatment of periodontitis. Toxicological studies are currently in progress.

Use of poly(ortho esters) in the controlled release of therapeutic agents

AbstractPoly(ortho esters) have been under development since 1970 and are the first polymer system that has been specifically designed for drug delivery applications. At this time, three distinctly different families of polymers have been described. One family is prepared by a transesterification reaction between diethoxytetrahydrofuran and a diol, another family is prepared by the reaction of polyols with diketene acetals and the third family is prepared by a transesterification reaction between a triol and an alkyl orthoacetate. The use of these polymers in drug delivery applications is illustrated with 5‐fluorouracil devices used in the treatment of human colorectal cancer xenografted in nude mice and with the delayed release of lysozyme, used as a model protein.

Synthesis and characterization of a new family of poly(ortho esters)

A previously reported synthesis of ointment-like poly(ortho ester)s prepared from a flexible triol and an alkyl orthoacetate has been extended to the preparation of solid materials by replacing the flexible triol with a rigid triol. The hydrolysis products of the polymer have been determined, and the hydrolysis has been shown to proceed exclusively by cleavage of the exocyclic alkoxy group of the ortho ester linkage. The lowest alkyl analog is crystalline, but the higher alkyl analogs are amorphous. The polymer is hydrolytically labile, and the rate of hydrolysis increases as the pH of the erosion medium decreases

An efficient and stereoselective synthesis of 3,4,6-tri- [formula omitted]-acetyl-α- [formula omitted]- glucopyranose 1,2-[ [formula omitted]-alkyl orthoacetates

The treatment of acetobromoglucose with N , N -dimethylformamide dialkyl acetals in the presence of tetra-n-butylammonium bromide affords the corresponding 1,2- exo -alkyl orthoacetates in a pure form and in almost quantitative yields.

Competitive formation of peracetylated α-l-arabinopyranosides and β-l-arabinopyranose 1,2-(alkyl orthoacetates) in Koenigs-Knorr condensations

Mixtures of peracetylated β-l-arabinopyranose 1,2-(alkyl orthoacetates) and the corresponding α-l-arabinopyranosides, in ratios as high as 1:1.3, have been obtained from primary, secondary, and tertiary alcohols and 2,3,4-tri-O-acetyl-β-l-arabinosyl bromide, by reaction in dichloromethane-diethyl ether (3:1) in the presence of silver oxide and anhydrous calcium sulfate. Orthoester formation decreased when dichloromethane was replaced by the less-polar chloroform or carbon tetrachloride, and also when diethyl ether was replaced by the more bulky dibutyl or di-isopropyl ethers. The product distribution, which is unusual for Koenigs-Knorr condensations involving 1,2-cis acylglycosyl halides in the presence of silver oxide, may be ascribed to competitive inhibition of glycoside formation by complexation of the intermediate glycosyl cation with ether and to solvent polarity effects.

ChemInform Abstract: ASPECTS OF THE CHEMISTRY OF GLYCOSIDES

AbstractReview: Bericht über einen Vortrag,der auf dem "IXth International Symposium on Carbohydrate Chemistry" vom 10.4.‐14.4.1978 in London, UK, gehalten wurde.

Aspects of the chemistry of glycosides

Observations dea1in with the synthesis and properties of glycosides are reported. A description is given of the use of 1—O—sul— fonyl derivatives, prepared from aldoses with sulfonic anhydrides, as intermediates for the synthesis of glycosides and glycosyl halides; the synthesis of disaccharides containing D—mannopyranosyl residues receives particular attention. Glycosyl esters are formed by reactions of carboxylic acids with 1,2—alkyl orthoacetates. Measurements of 13C—-H coupling are discussed in relation to studies on the orientation of glycosidic bonds in di— and oligosaccharides, and to anomalous spectral characteristics exhibited by glycosides of 5—thio—D—galactopyranose.

Über die orthoesterbildung als konkurrenzreaktion zur glykosylierung

1,2-(Alkyl orthoacetates) (orthoesters) were obtained in good yields from acetylated cis-glycosyl halides and alcohols in tetrahydrofuran in the presence of silver salicylate. The scope and the possible mechanism of the reaction were investigated. The presence of an intermediate oxonium ion ( 13) derived from the sugar derivative and tetrahydrofuran was deduced, from the occurrence of 4-bromobutyl 2,3,4,6-tetra- O-acetyl-β- d-glucopyranoside as a by-product of the reaction, and from semi-quantitative kinetic investigations. After an intramolecular reaction of this ion to form an acetoxonium ion ( 14), the reaction with an alcohol yields the orthoester ( e.g. 1- 7). In a similar manner, and in concurrence with direct glycosylation, ortho esters and products arising from orthoesters may be formed in the usual glycoside synthesis, using the reaction just described with the solvent or other nucleophiles.

Acetoxonium ions from acetoxyoxiranes and orthoesters: their conversion into ethylidene acetals, rearrangement, and solvolysis

The acid-catalysed ethylidenation of some methyl pentopyranosides has been studied and the configuration at the acetal carbon atom assigned by p.m.r. spectroscopy. There is a strong preference for the isomer in which the methyl group has the endo configuration. Several cyclic alkyl orthoacetates derived from methyl pentopyranosides have been prepared by orthoester exchange and the endo C-methyl isomer shown to preponderate. Treatment of vicinal acetoxyoxiranes and orthoacetates with boron trifluoride followed by lithium borohydride, or with diborane, yields ethylidene acetals in which the C-methyl group is endo. Rearrangements of the hexachloroantimonate salts of acetoxonium ions derived from methyl lyxo- and arabino-pyranosides, possessing trans-vicinal acetoxyl groups, have been studied. The ions having the arabino configuration are preferred in both the α and β series. The reaction of cyclic orthoacetates of methyl β- L-arabinopyranoside and some derivatives with dry acetic acid proceeds via an acyclic acetoxonium ion to yield only products having the L- arabino configuration.

Reaction products of ?-amino acids with alkyl orthoacetates

Reaction products of ?-amino acids with alkyl orthoacetates

Acid-catalysed [2H6]ethanolyses of alkyl orthoacetates: evidence for keten dialkylacetals as intermediates

N.m.r. analyses of 2,6-dichlorobenzoic acid-catalysed [2H6]ethanolyses of 1,1,1-triethoxyethane, 1,1,1-trimethoxyethane, and 2-ethoxy-2-methyl-1,3-dioxolan indicate that in each case the orthoacetyl methyl protons are subject to deuterium exchange. This exchange, however, proceeds much more slowly than the accompanying alkoxy-exchange. For 1,1,1-triethoxyethane, deuterium incorporation (47 atoms % at equilibrium) was confirmed by hydrolysis and mass-spectral analysis of the resultant ethyl acetate. A reaction mechanism in which a keten dialkylacetal is formed by elimination of a proton from an intermediate carboxonium ion is suggested to account for the observations.

Stereoselective ring-opening of β- D-mannopyranose 1,2-(alkyl orthoacetates)

The stability towards alkali of the 3,4,6-tri- O-acetyl-β- D-mannose 1,2-(alkyl orthoacetates) provides a route to the corresponding 3,4,6-tri- O-benzyl-β- D-mannose 1,2-(alkyl orthoacetates). Alkyl groups that have been incorporated onto the orthoacetate ring include methyl, isopropyl, and cyclohexyl. 3,4,6-Tri- O-benzyl-β- D-mannose 1,2-(methyl orthoacetate) ( 2) was hydrolyzed to 3,4,6-tri- O-benzyl- D-mannose; periodate oxidation converted this compound into 2,3,5-tri- O-benzyl- D-arabinose. Methanolysis of 2 led to methyl 3,4,6-tri- O-benzyl-α- D-mannoside ( 5) in high yield; methylation of 5, followed by debenzyiation and acetylation, afforded crystalline methyl 2- O-methyl-3,4,6-tri- O-acetyl-α- D-mannoside. An acid-catalyzed, stereoselective rearrangement of the 3,4,6-tri- O-benzyl-β- D-mannose 1,2-(alkyl orthoacetates) was observed. The resulting products were demonstrated to be the corresponding alkyl 3,4,6-tri- O-benzyl-α- D-mannosides.

Reaction of cholesterol with acetylated alkyl orthoacetates of D-glucopyranose

The condensation of acetylated alkyl orthoacetates of D-glucose with cholesterol has been studied. It has been shown that either transesterification or glycosylation may take place, according to the reaction conditions. Conditions have been found under which the sole direction of the reaction is glycosylation, leading to the 1, 2-trans-glycoside. A standard method for glycosylating complex alcohols with sugar orthoesters has been proposed.