Michael E. Evans

Acetal exchange reactions

Abstract The dimethyl acetals derived from acetone, pinacolone, acetophenone, and benzophenone undergo acid-catalyzed acetal exchange with methyl α- D -glucopyranoside. The major products are 4,6-acetals of the sugar; the minor products include methyl 2,3:4,6-di- O -isopropylidene-α- D -glucoside (using the acetone acetal), and isomeric methyl 2,3:4,6-di- O -(1- tert -butylethylidene)-α- D -glucosides (using the pinacolone acetal). These compounds are all examples of a five-membered acetal ring fused trans to a pyranoid ring. Treatment of methyl α- D -glucopyranoside with benzophenone dimethyl acetal gives methyl 6- O -(methoxydiphenylmethyl)-α- D -glucopyranoside in addition to the 4,6-acetal. The 4,6-acetals derived from the four ketones exhibit a wide range of sensitivity to hydrolysis by 75% (v/v) acetic acid.

Monomolar acetalations of methyl α-d-mannosides—synthesis of methyl α-d-talopyranoside

Abstract Methyl α- d -mannopyranoside (1 mole) reacts with 2,2-dimethoxypropane (1 mole), to give the 4,6-O-isopropylidene derivative (2) which rearranges to the 2,3-O-isopropylidene derivative (4). Compound4 can also be prepared by graded hydrolysis of methyl 2,3:4,6-di-O-isopropylidene-α- d -mannopyranoside. Successive benzoylation, oxidation, and reduction of4 provides a useful route to a number of d -talopyranoside compounds. Methyl α- d -mannofuranoside (1 mole) reacts with 1–2 moles of 2,2-dimethoxypropane to give the 5,6-O-isopropylidene derivative (16) in 90% yield.

6-Deoxy-d-glucose (d-Quinovose)

Publisher Summary This chapter discusses the lithium aluminum hydride reduction of methyl 6-chloro-6-deoxy- α - d -glucopyranoside. Lithium aluminum hydride (3.0 g) is added cautiously to a stirred solution of 7.0 g of methyl 6-chloro-6-deoxy- α - d -glucopyranoside in 350 ml of freshly distilled tetrahydrofuran. The mixture is heated under reflux for 18 hours and then cooled in ice and water while more lithium aluminum hydride is added. The cooled solution is applied to a 20 × 3.5 cm column of 80 g of Fisher cocoanut charcoal, which is then washed successively with 500 ml of water to remove hydrochloric acid and 1500 ml of 5% aqueous ethanol to elute 6-deoxy- d -glucose.

6-Chloro-6-deoxy-α-d-glucose: From Methyl α-d-Glucopyranoside by Reaction with Methanesulfonyl Chloride in N,N-Dimethylformamide

This chapter discusses the procedure involved in the preparation of 6-chloro-6-deoxy- d -glucose. It describes an experiment that involved the preparation of 6-chloro-6-deoxy- d -glucose by hydrolysis of methyl 6-chloro-6-deoxy- α - d -glucopyranoside in 10% hydrochloric acid for 3 hours at 100°; the yield was not stated. Methyl 6-chloro-6-deoxy- α - d -glucopyranoside was obtained in 8% overall yield from methyl α - d -glucopyranoside by a reaction sequence comprising formation of methyl 2,3,4-tri- O -acetyl-6- O -trityl-α- d -glucopyranoside, treatment of the latter compound with phosphorus pentachloride to give methyl 2,3,4-tri- O -acetyl-6-chloro-6-deoxy- α - d -glucopyranoside (31% yield), and deacetylation to form methyl 6-chloro-6-deoxy- α - d -glucopyranoside. For the preparation of 6-chloro-6-deoxy- d -glucose from its methyl glycoside, acetolysis is preferable to hydrolysis. The treatment of methyl 4,6- O -benzylidene- α - d -glucopyranoside with N -chlorosuccinimide may offer a route to 6-chloro-6-deoxy- d -glucose.