Robert J. Ferrier

A potentially versatile synthesis of glycosides

Abstract Phenyl 1-thio- D -glucopyranosides in the presence of mercury(II) salts are readily solvolysed to give alkyl D -glucopyranosides with inverted anomeric configuration. Methanolyses of the β and α anomers afford the methyl α and β-glycosides which were isolated in yields of 74 and 87%, respectively; n.m.r. examinations indicated that, whereas the β-glycoside was produced stereospecifically, the α-glycoside was formed together with ≈6% of its β isomer. The approach can be extended to the synthesis of complex glycosides (the α anomers of which are of special interest) as was illustrated by the preparation of cholestanyl and 1-naphthyl α- D -glucopyranoside and a disaccharide derivative.

Synthesis of 1,2-trans-related 1-thioglycoside esters

Boron trifluoride etherate catalyses the condensation of equimolar proportions of 1,2-trans-related monosaccharide peresters and thiols to provide a convenient synthesis of esters of 1,2-trans-1-thioglycosides. The reaction is efficient with alkyl, alkenyl, and some aryl thiols, and with aldopentose, aldohexose, and hexuronic acid acetates and benzoates. Some limitations are noted.

Substitution-with-Allylic-Rearrangement Reactions of Glycal Derivatives

Glycals (or usually their O-substituted derivatives) are readily converted into 2,3-unsaturated glycosyl compounds with O-, C-, N-, S- or otherwise linked substituents at the anomeric position. These products have been found to be useful for a range of synthetic purposes. In particular, the C-glycosidic compounds have served as readily available starting materials for the preparation of useful non-carbohydrate compounds. While these allylic rearrangement processes are usually conducted under the influence of Lewis acid catalysts, adaptations that involve activation of the allylic substituents of the starting glycals as leaving groups under neutral conditions have been developed. General features of the reactions are described as well as applications in synthesis and extensions of the basic processes.

SYNTHESIS AND REACTIONS OF UNSATURATED SUGARS

Publisher Summary This chapter discusses the synthesis and reactions of unsaturated sugars. Sugar derivatives that contain double bonds have been developed and used so extensively that they almost certainly constitute the most versatile category of carbohydrate compounds available for use in synthesis of unsaturated sugars. They may be applied both in the synthesis of complex members of the family and of a myriad enantiomerically pure noncarbohydrate compounds—notably, many of interest in medicinal chemistry. In addition, some unsaturated sugar derivatives have themselves been found to possess important therapeutic properties. The unnatural L-nucleoside inhibits reverse transcriptase and shows potent and selective anti-AIDS activity. This chapter surveys the chemistry of most of the important types of monosaccharide derivatives that contain single alkene groups—notably, the glycols that are extremely valuable starting materials for a vast range of synthetic transformations. It also discusses the preparation of the reactions of glycols, elaborates the synthesis of pyranoid and furanoid 2- and 3-Enes, and explains the chemistry of endo-Enes and exo-Enes.

Observations on the possible application of glycosyl disulphides, sulphenic esters, and sulphones in the synthesis of glycosides

Abstract Partial desulphuration of tetra-O-acetyl-β- d -glucopyranosyl phenyl disulphide with a phosphine derivative gave 40% of phenyl 2,3,4,6-tetra-O-acetyl-1-thio-α- d - glucopyranoside and a similar proportion of β- d -glucopyranosyl 1-thio-α- d -glucopyranoside octa-acetate, showing that this procedure is of limited value in α- d -thio-glucoside synthesis. Similar treatment of allyl tetra-O-acetyl-,β- d -glucopyranosyl sulphoxide caused abstraction of oxygen, rather than of sulphur, from the derived allyl glucosylsulphenate. The phenylsulphonyl group was not readily displaced from β- d -glucopyranosyl phenyl sulphone, except intramolecularly, nor could it be displaced from the tetrabenzyl ether. Elimination of benzyl alcohol from this compound afforded a new 1-(phenylsulphonyl)glycal derivative.

Syntheses and reactions of saturated and 2,3-unsaturated vinyl and 1'-substituted-vinyl glycosides

Abstract Reaction of tetra- O -α- d -glucopyranosyl bromide with bis(acylmethyl)mercurys [Hg (CH 2 COR) 2 ] afforded acetylated vinyl [by use of bis(formylmethyl)mercury] or 1′-substituted-vinyl β- d -glucopyranosides 11–13 in high yields. When used together with phenyl 4,6-di- O -acetyl-2,3-dideoxy-1-thio-α- d - erythro -hex-2-enopyranoside, these reagents gave analogous vinyl 4,6-di- O -acetyl-2,3-dideoxy- d - erythro -hex-2-enopyranosides 20–23 which, on treatment with Lewis acids, isomerised to the corresponding C -glycosyl compounds, i.e. (4,6-di- O -acetyl-2,3-dideoxy- d - erythro -hex-2-enopyranosy)acetaldehyde ( 24,25 ) or the corresponding glycosylated methyl ketones 26, 27 . A new route to C-3-branched glycals involves treatment of the above thioglycoside or the unsaturated vinyl glycosides with bis(benzoylmethyl)-mercury.

Syntheses of the fungicide/insecticide allosamidin and a structural isomer

A synthesis of the naturally occurring inhibitor of chitin metabolism, allosamidin 1, involves, as the key step, condensation between the allosamizoline derivative 39, prepared following oxyamination of the cyclopentene 19, and the disaccharide glycosylating agent 54 which was synthesised from 2-acetamido-2-deoxy-D-glucose. The structural isomer 59 of allosamidin is also reported. Brief biological test results obtained using isomers 1 and 59 are recorded.

Unsaturated carbohydrates. Part 29 Their application to the synthesis of stereospecifically doubly and triply branched derivatives

Abstract Treatment of 23-dideoxy-α- D - erythro -hex-2-enopyranosyl derivatives having 2-haloethyl substituents separately at O-1 and O-4 with tri- n -butyltin hydride together with a radical initiator gave products 16 and 56 with tetrahydrofuranyl rings cis -fused to C-1 C-2 and C-3 C-4 respectively. When these reactions which afforded compounds with stereospecific branch-points at C-2 and C-3 were carried out in the presence of methyl acrylate or with allyltri- n -butyltin as radical carrier the main products had the same bicyclic structures but had additional branch-points at C-3 and C-2 and possessed the α- D - gluco - and α- D - altro -configurations respectively. The D - gluco -allyl adduct 19 was converted into the 4-en-6-als 2526 and these products gave mainly a mixture of epimeric cyclopentano-furanopyrans (which were characterised as the acetates 2728) on treatment with tri- n -butyltin hydride and radical initiator. A notation is proposed for classifying intramolecular radical addition reactions of carbohydrates.

A route to functionalised cyclopentanes from 6-deoxyhex-5-enopyranoside derivatives

Abstract A route to the functionalised cyclopentenone derivative, (2 S )-( 2 3 )-dibenzyloxy-5-(hydroxymethyl)cyclopentene-4-enone ethylene acetal, has been developed from a deoxyinosose that is readily accessible. The carbocyclisation procedure was less efficient in affording (2 S )-(2, 3 4 ,5)-2,3,4,5-tetrahydroxy-2,3- O -isopropylidenecyclohexanone from 6-deoxy-1,2:3,4-di- O -isopropylidene-β- l - arabino -hex-5-enopyranose. Various reactions were carried out on (2 S )-(2,4, 5 3 )-2,3-di-benzoyloxy-5-hydroxy-4-toluene- p -sulphonyloxycyclohexanone ethylene dithioacetal.

Photo-bromination of carbohydrate derivatives. Part 3. C-5 bromination of penta-O-benzoyl-α- and -β-D-glucopyranose; a route to D-xylo-hexos-5-ulose derivatives and α-L-idopyranosides

Photo-bromination of penta-O-benzoyl-β-D-glucopyranose with bromine gives good yields of the 5-bromoderivative; the α-anomer reacts less well but also gives a crystalline 5-bromide. Hydrolysis gives D-xylo-hexos-5-ulose tetrabenzoate, which exists as the cyclic hydrate and reacts readily with alcohols and thiols to give tetra-O-benzoyl-5-hydroxy-β-D-glucopyranosides and 1-thin-analogues. These 5-hydroxy products can be methylated and the ‘diglycosides’ react with hydrogen chloride to afford 5-chloroglycoside esters from which α-D-idopyranosides are obtainable by reduction. Acetylation of a 5-hydroxyglycoside gives an acyclic product; a 5-hydroxythioglycoside gives some cyclic and some acyclic products.