Reverse aldol condensation

Base-induced eliminative ring fission, in which both the double bond and the sulfone function take part, has been observed in thiete dioxides253. The reaction can be rationalized in terms of initial Michael-type addition to the double bond of the ring vinyl sulfone, followed by a reverse aldol condensation with ring opening. The isolation of the ether 270c in the treatment of 6c with potassium ethoxide (since the transformation 267 -> 268 is not possible in this case) is in agreement with the reaction mechanism outlined in equation 101253. 

Cleavage of Fructose 1,6-Bisphosphate The enzyme fructose 1,6-bisphosphate aldolase, often called simply aldolase, catalyzes a reversible aldol condensation (p. 485). Fructose 1,6-bisphosphate is cleaved to yield two different triose phosphates, glyceraldehyde 3-phosphate, an aldose, and dihydroxyacetone phosphate, a lcetose ... 

These reactions have several features in common. They all involve phosphate esters of aldoses or ketoses, and they resemble aldol or reverse-aldol condensations. Their mechanisms will not be considered here, but are discussed more explicitly in Sections 20-10A, 20-10B, and 25-10. Their summation is... 

Kraft cooking of dihydrodehydrodiconiferyl alcohol (I) as a model for the phenylcoumaran system shown to be present in native lignin (/, 2), resulted (3, 13) in the opening of the hydrofuran ring and splitting ofF of formaldehyde, probably through a reverse aldol condensation of an intermediate quinonemethide (77, 18). The resulting p,0 -dihydroxystilbene... 

Primary amine catalysis (usually involving a lysine residue) has been recognised to play an important role in various enzyme-catalysed reactions. Examples are the conversion of acetoacetate to acetone catalysed by acetoacetate decarboxylase, the condensation of two molecules of S-aminolevulinic acid catalysed by -aminolevulinic deshydratase during the biosynthesis of porphyrins, and the reversible aldol condensation of dihydroxy-acetone phosphate with glyceraldehyde which in the presence of aldolase yields fructose-1-phosphate (64) (For reviews see, for example, Snell and Di Mari,... 

Although all of these methods suffered from deficiencies (difficulties of synthesis of starting materials, low yields, and more often than not the formation of mixtures of products requiring tedious separation procedures), they still find ample application for the preparation of many C-substituted imidazoles (e.g. 4-alkyl, 4,5-dialkyl, 2,4,5-trialkyl). The old Debus (or Radziszewski) method is still useful for preparing such compounds as 4-methyl- (132) and 2,4-dimethyl-imidazoles (133) using pyruvaldehyde (Scheme 71). However, alkaline fission of the pyruvaldehyde can result in a mixture of products. When pyruvaldehyde is treated alone with aqueous ammonia there are three main products (132), (133) and 2-acetyl-4-methylimidazole. Reversed aldol condensations cause degradation of the pyruvaldehyde, and subsequent cyclization of the fragments as in Schemes 71 and 72 accounts for the products. 

Formaldehyde liberation from y-methylol groups by alkaline cleavage of the p-y C-C bond has been observed, and the action of hot alkali on lignin to form vanillin by cleavage of the a-p C-C bonds is well known. The simultaneous formation of acetaldehyde in the latter case results from a reverse aldol condensation. Traces of guaiacol found after alkaline hydrolysis of wood may result from cleavage of the C-C bond between the a carbon and the ring. 

Another type of cleavage during electrolysis occurs as a slow step in the reduction of certain )6-diketones in DMSO [19] the primarily formed radical dimerizes to a pinacol that, catalyzed by the base generated during the electrolysis, is cleaved in a reverse aldol condensation to an a-diketone. 1,3-Diphenyl-1,3-propanedione is thus reduced in DMSO according to ... 

Fructose 1-phosphate is further metabolized to dihydroxyacetone phosphate (DHAP) and glyceraldehyde by the hepatic isoform of the enzyme aldolase, which catalyzes a reversible aldol condensation reaction. Aldolase is present in three different isoforms. Aldolase A is present in greatest concentrations in the skeletal muscle, whereas the B isoform predominates in the liver, kidney, and intestine. Aldolase C is the brain isoform. Aldolase B has similar activity for either fructose 1,6-bisphosphate (F16BP) or FIP however, the A or C isoforms are only slightly active when FIP is the substrate. 

N-Acetylneuraminic acid aldolase catalyzes the reversible aldol condensation of pyruvate (23) and N-acetylmannosamine (22 ManNAc) to form N-acetylneuraminic acid (24 NeuAc N-acetyl-5-amino-3,5-dideoxy-D-glycerogalacto-2-nonulopyronic acid Scheme 6).80-83 In vivo the enzyme has a catabolic function and the equilibrium for this reaction is near unity the presence of excess pyruvate can shift this equilibrium. NeuAc and other derivatives of neuraminic acid are termed sialic acids. These compounds are found at the termini of mammalian glycoconjugates and play an important role in cellular recognition.84-89 The production of analogs of NeuAc is a point of great interest to synthetic and medicinal chemists. The enzymatic approach has not been fully explored but it may be a practical alternative to the chemical synthesis of certain sialic acids.89... 

In aldol condensation, aldehydes and ketones react to form a larger molecule (Section 14.4). This reaction is a reverse aldol condensation. The large ketone sugar fructose-l,6-bisphosphate is broken down into dihydroxyacetone phosphate (a ketone) and gIyceraldehyde-3-phosphate (an aldehyde). 

Aldolase catalyzes the reverse aldol condensation of fructose-1,6-6i.jphosphate to glyceraldehyde-3-phosphate and dihydroxyacetone phosphate. 

Aldolases - Aldolases catalyze reversible aldol condensations of su-gars. A well-studied enzyme is fructose-1,6-dlphosphate aldolase from rabbit muscle. This enzyme exhibits a high specificity for dihydroxy-acetone phosphate as the nucleophile, but tolerates a range of aldehydes as electrophiles (Scheme II).This broad specificity allows synthesis of sugars such as 6-deoxyfructose and Isotopically labeled glucose... 

Pilosinine is a monoacidic base, and is optically active, the rotatory power falling rapidly in aqueous solution. It gives no color with diazo-benzenesulfonic acid and does not immediately decolorize permanganate. In its physical and chemical properties it closely resembles pilocarpine and isopilocarpine, and accordingly Pyman (46) proposed structures I and II for pilosine and pilosinine respectively, the alkaline degradation of pilosine being attributed to a reversed aldol condensation of a known type (177). On this basis, anhydropilosine has structure III. As pilosine... 

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