Sugar aldehyde condensations

Fig. 11. Sugar aldehydes condensed directly on pyrrole derivatives by Lindsey s chemistry.

B. Grzcszczyk, K. Dziewiszek, S. Jarosz, and A. Zamojski, Asymmetric induction in acid-catalysed condensations of sugar aldehydes with furan and 2-methylfuran, Carbohydr. Res., 145 (1985) 145-151. 

The three-component reaction of indole (2) with sugar hydroxyaldehyde 281 and Meldrum s acid 282, with a catalytic amount of D,L-proline, afforded the 3-substitution product 283 as a single isomer [203]. The substituent possesses the czs-fused furo [ 3,2- b ] pyranonc skeleton. The proline catalyzes the Knoevenagel condensation of the sugar aldehyde 281 and Meldrum s acid 282 to provide the alkylidene derivative 284 of Meldrum s acid. Then a diastereo-selective Michael addition of indole and an intramolecular cyclization of this adduct 285 with evolution of carbon dioxide and elimination of acetone furnish the furopyranone in one-pot (Scheme 62). 

Isomerism at the acetal carbon atom is theoretically possible in five-membered acetal rings formed when pyranose or furanose sugars are condensed with aldehydes. For furanose derivatives, the isomerism is exo-endo, and the superior stability of exo isomers ensures that one isomer only will be obtainable, and this of the exo configuration. " 1,2-0-Benzylidene-a-D-glucofuranose " therefore has the complete configuration XLV. If the... 

A related domino process was used for the synthesis of coumarin derivatives that contain sugar-fused moieties. In the presence of NaOAc and HOAc, the reaction of coumarin 159 with prenylated sugar aldehyde 160 produced 161 in 82% yield (equation (5)) (04TL3493). A variety of 1,3-dicarbonyl compounds also participated in the reaction and provided tandem condensation/cycloaddition products in good yields (70-80%). 

A variety of 2-substituted 2//-chromenes can be obtained from the facile reaction of 2-hydroxybenzaldehydes with vinylboronic acids in ionic liquid solvents <04SL2194>. In a one-pot sequence also in an ionic liquid, a Knoevenagel condensation between O-prenylated salicylaldehydes and 4-hydroxycoumarins is followed by an intramolecular hDA reaction to yield ci5-fused chromano[4, 3 4,5]pyrano[3,2-c]coumarins e.g. 20 small amounts of the corresponding chromone are also formed <04S1783>. In like manner, cii-fused furopyranopyran derivatives have been obtained from sugar aldehydes <04TL3493>. 

The introduction of the a-keto acid function on the way to the ulosonic acids is a main problem of their syntheses. By analogy with the biosynthetic pathway, the aldol reaction between sugar aldehydes and a pyruvate equivalents seems to be the most simple and versatile. As it has been demonstrated by Comforth [74] in the first chemical synthesis, the reaction of arabinose and oxalacetic acid as pyruvate equivalent, followed by decarboxylation afforded KDO, albeit in low yield. This condensation has been optimized by use of Ni(II) catalyst for the decarboxylation [75], In this case, reaction of D-mannose and oxalacetic acid gave KDN (11) and its D-manno epimer 37 in 70% yield [75] (Scheme 12). 

Condensation of A/-alky lade nine with 2-deoxyribose (654) in a phosphorus pentoxide mixture gave 655 via a probable Michael-type addition to an a,)3-unsaturated sugar aldehyde formed in situ from 2-deoxyribose. Reduction of 655 gave 656(92JHC511). Neither 655 nor 656showed any significant activity against HSV-1,... 

Two hydroxyls of a carbohydrate molecule may react with an aldehyde with the formation of a cyclic acetal. These products are known as 0-aryli-dene or 0-alkylidene derivatives of sugars. Acetone condenses similarly to give 0-isopropylidene (acetone) derivatives 2a). 

In an attempt to increase the water solubility of carborane - antibody complexes, the dialdehyde (23) and several other sugar aldehydes were treated with lithiated dicarba c/r o-dodecaboranes (29). The reactions were reasonably stereoselective, giving erythro- and tAreo-products, e.g., compounds (30) in ca. 4 1 ratios. From the same starting compound (23) the 1,6-C-linked disaccharide (33) was prepared by fluoride ion mediated condensation with peracetylated -C-glucopyranosyl nitromethane (31) followed elaboration of the... 

Aldolases cataly2e the asymmetric condensation of intermediates common in sugar metaboHsm, such as phosphoenolpymvic acid, with suitable aldehyde acceptors. Numerous aldolases derived from plants or animals (Class I aldolases) or from bacteria (Class II) have been examined for appHcations (81). Efforts to extend the appHcations of these en2ymes to the synthesis of unusual sugars have been described (2,81). 

Frequently, it is the bisulfite addition product that is treated with CN. This method is especially useful for aromatic aldehydes, since it avoids competition from the benzoin condensation. If desired, it is possible to hydrolyze the cyanohydrin in situ to the corresponding a-hydroxy acid. This reaction is important in the Kiliani-Fischer method of extending the carbon chain of a sugar. 

Another example of the ability of proteinogenic amino acids, small peptides, and amines to catalyse the formation of new C-C bonds has been demonstrated by Weber and Pizzarello they were able to carry out model reactions for the stereospecific synthesis of sugars (tetroses) using homochiral L-dipeptides. The authors achieved a D-enantiomeric excess (ee) of more than 80% using L-Val-L-Val as the peptide catalyst in sugar synthesis (in particular D-erythrose) via self-condensation of glycol aldehyde. 

The third hypothesis (C) is that reaction takes place through an aldol condensation between the ethyl acetoacetate and the carbonyl form of the sugar. There is some precedent indicating that it is possible for /3-ketonic esters to undergo aldol condensation. These compounds react mole to mole with the aliphatic aldehydes and afford unsaturated substances, which could be formed via an aldol condensation with subsequent dehydration. 

Condensation of /V-benzylhydroxylamine with various aldehydes and ketones in CH2CI2 in the presence of anhydrous magnesium sulfate has made it possible to carry out successful syntheses of a great number of chiral and achiral sugar-containing N-benzylnitrones (partly presented in Table 2.3) (191-208). 

Oxidative processes (route B) represent another common route to triazolopyridines (compounds described in Schemes 54 and 55). These preparations all start from aldehyde hydrazones and use different oxidative reagents for the cyclization (Table 2). Generally, those conditions are milder than condensation methods. Moreover, the oxidizing reagents are compatible with other moieties, even the sugar-derived polyol 209. In the case of compound 208, the hydrazone (major diastereomer) was obtained by tautomerization of the corresponding enhydrazine, the... 

Henry reactions of nitro sugars can be promoted by catalytic amounts of mild bases and it has widely extended the use of triethylamine. A recent example involves the condensation of sugar derived a,p-unsaturated aldehyde 15 with nitromethane in the presence of triethylamine, to give... 

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