Synthesis of 2,3,4,6-Tetra-O-Acetyl-1,5-Anhydro-D-lyxo-Hex-1-enitol and its Conversion into a Hex-3-enopyranosid-2-ulose Analogue of Levoglucosenone

MANZANO V.; REPETTO E.; UHRIG M. L.; BARATH M.; VARELA O.

Carbohydrate Chemistry: Proven Synthetic Methods

Taylor & Francis

Año: 2011; p. 291 - 298

The α,β-unsaturated carbonyl group is found in a large number of natural and synthetic products. This functionality is commonly related to a wide range of biological activities, such as antitumor, antiviral, antimicrobial, and gastric antiulcer activities.1 Particularly, sugar enones have become important synthetic targets not only due to their bioactivity but also for their use as building blocks in the synthesis of varied targets.1,2 The usefulness of sugar enones as chiral building blocks relies upon the fact that they posses olefinic and carbonyl unsaturations to which a number of wellestablished reactions may be applied. In addition, because of the chiral environment generated by the remaining stereocenters, reactions applied to the enone system are usually highly diastereoselective. Levoglucosenone and isolevoglucosenone are common sugar-derived enuloses that have been employed as dienophiles in Diels?Alder cycloadditions3 and as Michael acceptors in the synthesis of thiodisaccharides.4 While levoglucosenone is usually obtained in a very low yield, as one of the products of pyrolysis of cellulose, we have described a mild procedure for the preparation of analogous 3-enopyranosid-2-uloses from hexoses5 and pentoses,6 via the corresponding 2-acetoxyglycal derivatives. These compounds undergo a double allylic rearrangement by the tin(IV) chloride-promoted glycosylation to give the enones in good yields. The 3-enopyranosid-2-uloses proved to be convenient dienophiles in Diels?Alder reactions with butadienes and cyclic dienes.6?10 They have also been employed as Michael acceptors of thiols in the synthesis of glycosides of 3-deoxy-4-thiopyranosid-2-ulose and 3-deoxy-4-thiopyranosides.11,12 This reaction has been extended to the synthesis of thiodisaccharides as sugar mimetics and enzyme inhibitors. Thus, the conjugate addition of 1-thioaldoses to sugar enones led to 3-deoxy-4-S-(1→4)thiodisaccharides formed by hexopyranose units13 or their analogues constituted by pentoses and hexoses,14 or having a furanose as nonreducing end.15,16 The methodology has also been employed for the synthesis of 4,6′-thioether-linked disaccharides as hydrolytically stable glycomimetics.17 Reduction of the carbonyl of the 3-en-2-ulopyranoses followed by oxidation of the double bond afforded sugar 3,4-epoxides, that underwent nucleophilic substitution by 1-thioaldoses to give (1→3)- and (1→4)-linked thiodisaccharides.18 Naturally occurring amino deoxy sugars, constituents of antibiotics, have been synthesized from hex-3-enopyranosid-2-uloses.19,20 We describe herein a straightforward and high-yielding synthesis of benzyl 3,4-dideoxy-α-d-glycero-hex-3-enopyranosid-2-ulose (4) from d-galactose, via the 2,3,4,6-tetra-O-acetyl-1,5-anhydro-d-lyxo-hex-1-enitol (3). A convenient preparation of this intermediate is also described, as glycal derivatives themselves are useful chiral synthons.2,21 Glycal 3 has been prepared in low yield a long time ago,22 and it has been determined that in the crystalline state it adopts the 4H5 half-chair conformation.23