Unsaturated sugars preparation

The main interest in unsaturated sugars prepared by the Wittig reaction (and described in this Section) has concerned their synthetic utilization. The pathways of the latter depend on the structure of the unsaturated precursor. In the case of C-glycosylated alkenes, addition to the double bond (mainly hydration and hydrogenation) leads to a branched-chain or long-chain sugar, although correct choice of the reactant to be added may provide a variety of derivatives. 

Methyl glycosides of 2 deoxy sugars have been prepared by the acid catalyzed addition of methanol to unsaturated sugars known as glycals... 

Tronchet, J.M.J., Neeser, J.-R., Gonzalez, L., and Charollais, E.J., Preparation of unsaturated sugars phosphonates using nucleophilic conjugate addition, Helv. Chim. Acta, 62, 2022, 1979. 

Some 2,3-unsaturated sugars have also been prepared by the reaction of 2-iodinated carbohydrates with sodium cobalt tetra-carbonyl and carbon monoxide.188 Methyl 3,4,6-tri-0-acetyl-2-deoxy-2-iodo-/3-D-glucopyranoside (149) in ether reacts at room temperature to give, in high yield, methyl 4,6-di-0-acetyl-2,3-dideoxy-/3-D-eri/thro-hex-2-enopyranoside (150). Under the same reaction conditions,... 

L-erythronic acids, respectively, and D-xylose to D-threonic acid.44 Isbell et al. elucidated the mechanism of this process45 (see the following Chapter). Degradation to a lower aldonic acid can be achieved by oxidation of an unsaturated sugar derivative. The method of Reichstein et al.46 for the preparation of L-threono-1,4-lactone by permanganate oxidation of 5,6-0-isopropylidene-L-ascorbic acid was improved by Perel and Dayton to afford the crystalline lactone in 65% yield.47... 

A simple and efficient method for rearranging 2,3-anhydro carbohydrates to unsaturated sugars under mild conditions has been reported (Scheme 127).191 High stereoselectivity provides a method for the preparation of unsaturated carbohydrate derivatives. 

Treatment of 1,2-C-methylene carbohydrates, prepared by cyclopropanation of unsaturated sugars, with Lewis acids and trapping of the intermediate oxonium ion with a nucleophile is a convenient route to 2-substituted-2,3,6,7-tetrahydrooxepines <95TL683i>. Thus rearrangement of (55) with TMSOTf in acetonitrile in the presence of MeCN affords (56). The trapping nucleophile may be a substituent of the original carbohydrate, as demonstrated by the conversion of (57) into the bridged bicyclic oxepine (58). 

Intramolecular substitutions offer a convenient and stereoselective method for the introduction of amino functionalities. A strategy for the preparation of vicinal m-hydroxy amino moieties entails the halocy-clisation of allylic trichloroacetimidates.77 Conversion of the hydroxyl of unsaturated sugar derivatives into a trichloroacetimidate, followed by Ar-bromosucciniinide (NBS) or JV-iodosuccinimide (NIS) mediated intramolecular cyclisation, gives bromo- and iodo-oxazoline derivatives (Scheme 3.13a). The oxazoline can be hydrolysed with mild acid to unmask the amino functionality, and the halogen can be removed by treatment with tributyltin hydride. 

Generally two main classes of unsaturated sugars in which (1) the anomeric carbon atom is involved in a double bond (glycals) and (2) the unsaturation is placed between other carbon atoms are known. One has to discuss also derivatives with the exo- and enclo-unsaturated bonds (either oleflns/dienes or acetylenes). Another class of unsaturated monosaccharides is represented by the open-chain sugars with the double bond(s) and/or triple bond present in the molecule. The examples of different types of unsaturated sugars are shown in O Fig. 2. Compounds such as glycals will not be discussed here, unless they are used as substrates for the preparation of other, non-anomeric, unsaturated derivatives. 

In this section the selected and most representative examples (including also several older ones) of the preparation of unsaturated monosaccharides with the double hond present in the sugar ring will be described. The material will be divided into three main classes 2,3-, 3,4-, and 4,5-unsaturated sugars in both pyranose and furanose forra... 

In this section only the direct synthesis of 2,3-unsaturated sugars, in which the double bond is created will be presented. Numerous syntheses of these valuable compounds have been described in the literature. One of the most important classes of such derivatives are 2/3 -dideoxy-2, 3 -didehydronucleosides which possess a broad spectrum of biological activity. Two different approaches to 2, 3 -dideoxy-2, 3 -didehydro-thymidine (d4T) illustrate the general methodology of their preparation. 

Base-catalyzed isomerization of epoxides into allylic alcohols is a method of choice for the preparation of unsaturated sugars olefin 10 was prepared by treatment of oxirane 9 with a strong base. This process is similar to the Horwitz s)uithesis of d4T presented in Scheme 7. The Tipson-Cohen methodology is frequently applied for the synthesis of 2,3-unsaturated sugars as shown in Scheme 10 such reduction might be performed also under microwave irradiation [6]. 

The key-step in the synthesis of a unsaturated sugar 34 bearing two amino groups (a scaffold which were used for the preparation of peptides with aromatic rings) was realized by the rearrangement of the adduct 33 readily prepared from D-glucal 23 (O Fig. 5) [43]. 

Another interesting example of the preparation of unsaturated O- and C-glycosides 36 was presented recently [44]. This was based on the Sn2 attack of the nucleophile on unsaturated epoxide 35. Substitution at C-1 proceeded with simultaneous migration of the double bond and opening of the three-member ring providing 2,3-unsaturated derivative 36 (O Scheme 20). Conversion of 4-deoxy-2,3-unsaturated sugars into 3,4-unsaturated ones reported by Banaszek and Zamojski already in 1972 [3] was one of the key-steps in total s)mthesis of monosaccharides by a hetero Diels-Alder approach. 

The carbocycles substituted at the double bond (with for example, an alkox)methylene group) can also be prepared from the appropriately functionalized unsaturated sugars. Synthesis of a-glucosidase inhibitor—valienamine—was realized from unsaturated sugar chirons as shown in Fig. 9 [86]. 

Of course, this chapter does not pretend to be comprehensive. The idea behind this chapter was for the authors to show how to prepare the desired unsaturated sugars using proper method(s) and (eventually) how to apply these synthons in the synthesis of important targets. 

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