Carbohydrates aldol addition

Alditol (Section 25 18) The polyol obtained on reduction of the carbonyl group of a carbohydrate Aldol addition (Section 18 9) Nucleophilic addition of an aldehyde or ketone enolate to the carbonyl group of an aide hyde or a ketone The most typical case involves two mole cules of an aldehyde and is usually catalyzed by bases... 

Cleavage reactions of carbohydrates also occur on treatment with aqueous base for prolonged periods as a consequence of base catalyzed retro aldol reactions As pointed out m Section 18 9 aldol addition is a reversible process and (3 hydroxy carbonyl com pounds can be cleaved to an enolate and either an aldehyde or a ketone... 

Esterification. The hydroxyl groups of sugars can react with organic and inorganic acids just as other alcohols do. Both natural and synthetic carbohydrate esters are important in various apphcations (1,13). Phosphate monoesters of sugars are important in metabohc reactions. An example is the enzyme-catalyzed, reversible aldol addition between dibydroxyacetone phosphate [57-04-51 and D-ylyceraldehyde 3-phosphate [591-57-1 / to form D-fmctose 1,6-bisphosphate [488-69-7],... 

In general, chiral propanoates providing simple diastereoselectivity (in favor of yyn-aldols), combined with a reasonable degree of auxiliary-induced stereoselectivity, are rare. Numerous terpenoid- and carbohydrate-derived propionates do not display satisfactory syn selectivity60. Similarly, the titanium(IV) chloride promoted aldol addition of the following JV-metbylephe-drine derived silylketene acetal leads to the formation of the. mi-adduct in the moderate diastereomeric ratio of 78 22 (syn-adduct sum of the other stereoisomers)61. 

This is a type of aldol addition (known as biological aldol addition) and is one of the reaction in the metabolism of carbohydrates by the glycolic pathway. 

Asymmetric C-C bond formation is the most important and most challenging problem in synthetic organic chemistry. In Nature, such reactions are facilitated by lyases, which catalyze the addition of carbonucleophiles to C=0 double bonds in a manner that is classified mechanistically as an aldol addition [1]. Most enzymes that have been investigated lately for synthetic applications include aldolases from carbohydrate, amino acid, or sialic acid metabolism [1, 2]. Because enzymes are active on unprotected substrates under very mild conditions and with high chemo-, regio-, and stereoselectivity, aldolases and related enzymes hold particularly high potential for the synthesis of polyfunctionalized products that are otherwise difficult to prepare and to handle by conventional chemical methods. 

K. L. Yu and B. Fraser-Reid, Facial-selective carbohydrate-based aldol additions, J. Chem. Soc. Chem. Commun. p. 1442 (1989). 

One of the reactions in the metabolism of carbohydrates by the glycolytic pathway is a type of aldol addition. In this reaction D-fructose (as the 1,6-diphosphate ester) is formed from D-glyceraldehyde and 1,3-dihydroxypro-panone (both as monophosphate esters). The process is readily reversible and is catalyzed by an enzyme known as aldolase ... 

The carbon that lost a proton is now a nucleophilic center and can therefore react with formaldehyde. As mentioned above, formaldehyde has an electrophilic center on carbon. Therefore, the carbon of formaldehyde can react with the nucleophilic carbon on the enolate of glycolaldehyde to form a new compound containing three carbon atoms, a three-carbon carbohydrate called glyceraldehyde. The overall reaction sequence is often called an aldol addition reaction, here of formaldehyde and glycolaldehyde. 

Eyrisch, O, Sinerius, G, Fessner, W-D, Eacile enzymic de novo synthesis and NMR spectroscopic characterization of D-tagatose 1,6-bisphosphate, Carbohydr. Res., 238, 287-306, 1993. Henderson, I, Sharpless, KB, Wong, C-H, Synthesis of carbohydrates via tandem use of the osmium-catalyzed asymmetric dihydroxylation and enzyme-catalyzed aldol addition reactions, J. Am. Chem. Soc., 116, 558-561, 1994. 

Recently, the rapid preparation of carbohydrates has been facilitated by a synthetic route based on aldol coupling of three aldehydes used for the de novo production of polyol differentiated hexoses in only two chemical steps. The dimerization of alpha-oxyaldehydes, catalyzed by L-proline, is followed by a tandem Mukaiyama aldol addition-cyclization step catalyzed by a Lewis acid. Differentially protected glucose, allose, and mannose stereoisomers can each be selected, in high yield [46]. Microwave irradiation is becoming an increasingly popular method of carbohydrate synthesis and has been the subject of a recent review [47]. 

The synthesis of (-t-)-exo-brevicomin (Fig. 14.1-4) was the first example of the use of RAMA to synthesize a non-carbohydrate derivative1771. RAMA was employed to catalyze the key aldol addition step, in which the two chiral centers of the target molecule were established. RAMA has also been employed for the synthesis of a key fragment of (+) aspicilin17X1, and for that of acyclic polyols1791. Single aldol condensation on remote dialdehydes has also been achieved1801. 

I. Aldolic addition and the Mannich reaction (Vol. I. p. 186) The aldolic I addition reaction of nitroalkanes with carbohydrates (specifically aldoses) continues to be an important reaction in sugar chemistry which according to Baer i ) in some respects surpasses in versatility limil Fischer s classical cyano-[hydrin syntliesis. Particularly noteworthy are publications by Baer and Kovaf 1144, 45], Funubaski. Yoshimura and co-workers (46 51] and other Japanese [workers (52], Russian workers [53, 54] and Bilik (55]. 

A-acetyl neuraminic acid lyase (NAL) catalyzes the reversible aldol addition of N-acetylmannosamine to pyruvate to produce A-acetylneuraminic acid, a sialic acid. Sialic acid is an essential component of complex carbohydrates which are of paramount importance as recognition signals in a variety of biological process, such as parasite invasion, infectivity and survival of the invading organism in the host. Hence, sialic acids mimetics, such as the commercial Oseltamavir, Relenza and... 

Markert M, Mahrwald R (2008) Total Syntheses of Carbohydrates Organocatalyzed Aldol Additions of Dihydroxyacetone. Chem Eur J 14 40... 

Highly intriguing accounts on enzymatic DCL generation applied to a carbohydrate-binding protein have also been reported [50, 51]. Using the N-acetyl-neuraminic acid aldolase (sialic acid aldolase), reversible aldol addition of three or four different carbohydrates to pyruvate was catalyzed, yielding small DCLs of... 

Here we recount the latest research on chemoenzymatic multistep and cascade strategies for the synthesis of iminocyclitols, carbohydrates, and deoxysugars from N-protected ami noaldehydes, hydroxyaldehydes, and simple alkylaldehydes, respectively. The key step in all of them is the stereoselective aldol addition reaction of dihydroxyacetone phosphate (DHAP) and its unphosphorylated analogs to the acceptor aldehydes using DH AP-dependent and dihydroxyacetone- (DH A)-utilizing aldolases, respectively, as biocatalysts. 

For example, the first step in glycolysis is an Sj. 2 reaction, the second step is identical to the enediol rearrangement that students learned when they studied carbohydrate chemistry, the third step is another Sj 2 reaction, and the fourth step is a reverse aldol addition. 

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