Carbon hemiacetal activation

Another mode of carbon-based activation of hemiacetals relies on carbonyl-centered electrophiles 89 (Scheme 3.14). These reagents have demonstrated the highest efficiency for disaccharide synthesis among electrophilic carbon activating agents. In the event, the hemiacetal 1 is activated with electrophile 89 for in situ... 

Reactions of Vinyl Ethers. Vinyl ethers undergo the typical reactions of activated carbon—carbon double bonds. A key reaction of VEs is acid-catalyzed hydrolysis to the corresponding alcohol and acetaldehyde, ie, addition of water followed by decomposition of the hemiacetal. Eor example, for MVE, the reaction is... 

From prior attempts at FruA-catalyzed DHAP additions to glyoxal or glutaric dialdehyde no product had been isolated, probably because the dialdehydes can cause cross-linking of the protein and thereby irreversibly destroy its enzymatic activity. On the other hand, hydroxylated aldehydes were assumed to form stable intramolecular hemiacetals in aqueous solution, which may mask the reactivity of free dialdehydes. Using the branched-chain glutaric dialdehyde 38 as a potential precursor to carbon-linked disaccharide mimetics (Scheme 2.2.5.14), we... 

While checking a sample of 2,5-anhydromannose-6-P for fructose-6-P by incubating it with phosphofructokinase and MgATP, we discovered that this aldehyde, which is sterically hindered from forming an internal hemiacetal, induced an ATPase activity (6). Since aldehyde hydration shows a large inverse equilibrium isotope effect of 0.73 when the hydrogen on the carbonyl carbon is replaced by deuterium (7,8), 2,5-anhydroman-nose-6-P-l-d will be 60% hydrated, compared to 52% hydration of the unlabeled aldehyde. If the free aldehyde were the activator, 48% of the unlabeled and 40% of the deuterated compound would be active, and a normal deuterium isotope effect of 0.48/0.40 = 1.2 would be seen on V/K (the apparent first order rate constant) for the activator, while if the hydrate were the active form, an inverse isotope effect of 0.52/0.60 = 0.87 would be seen. The observed value of 1.23 0.03 showed that the free aldehyde and not the hydrate was the activator (6). 

Djerrassi and co-workers suggested a mechanism for the oxygen introduction step, which involved formation of a hemiacetal intermediate caused by the fission of the carbon-sulfur bond followed by attack with hydroxide ion, as illustrated in Scheme 13.14.161,162 The mechanism is supported by the preservation of chiral center when an optically active ethylenehemithio acetal was subjected to desulfurization to regenerate the ketone. 

The reverse situation, in which the phenol acts as the nucleophile attacking activated carbohydrate hemiacetals, has also found several practical applications preparing 0-aryl glycosides [388]. However, this situation implies an attack at the anomeric carbon and not at the anomeric oxygen. 

Since a hemiacetal is formed so easily from a carbonyl compound and alcohol, it is not surprising to find that carbohydrates (polyhydroxy derivatives of aldehydes and ketones) frequently exist as cyclic structures in which a hemiacetal linkage is formed intramolccularly. Furthermore, since hemiacetal formation is a reversible process, many carbohydrates exhibit the phenomenon of mutarotation. The liberation of the free aldehyde (V) from the internal hemiacetal of the sugar (IV) destroys the optical activity of the hemiacetal carbon atom (in this case carbon 1), and reformation results in the formation of an equilibrium mixture of two diastereoisomers. 

However, this sequence can be reversed. - Thus, the activated cyclopropane can be de-protonated by lithium diisopropylamide, reacted with an appropriate ketone and opened by various methods such as treatment with acid or desilylation with fluoride. Using this reaction sequence, y-lactones 52 with various substituents can be obtained by the intramolecular attack of the ketone oxygen on the siloxy-substituted carbon followed by oxidation with pyridinium chlorochromate. The cyclic hemiacetal intermediates 53 can be converted to the tetrahyd-rofuran derivatives 55 by deoxygenation with triethylsilane/boron trifluoride. 

The linalool oxides (109) are probably the oldest known of this group (Vol. 2, p. 165). They have been isolated after the action of Streptomyces albus on linalool (28), the optical activity at C-2 of the furan is the same as that of the starting linalool. This work also points out that rotations of the linalool oxides are different when measured neat or in solution. The oxidized linalool oxide 889 has been found in grape juice. It was synthesized by the action of silver carbonate on the dihydroxylinalool 108 (also occurring in grape juice), and dehydrating the hemiacetals 890 thus formed. ... 

D-glucopyranose is a cyclic hemiacetal, which is an equilibrium with its open-chain form that contains an active aldehyde group. In contrast, the anomeric carbon atoms of glucose and fructose are joined in an a-glycosidic linkage in sucrose. Hence sucrose is not in equilibrium with an active aldehyde or ketone form. 

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