Lactones aldehyde hemiacetals

Oxidation of the C] aldehyde (hemiacetal) to the carboxylic acid (lactone). 

The most widely used reagent for partial reduction of esters and lactones at the present time is diisobutylaluminum hydride (DiBAlH).83 By use of a controlled amount of the reagent at low temperature, partial reduction can be reliably achieved. The selectivity results from the relative stability of the hemiacetal intermediate that is formed. The aldehyde is not liberated until the hydrolytic workup and is therefore not... 

Another method for the alkylidenation of aldonolactones uses addition of organ-ometallic reagents [78]. For example, Lin et al. [85] described an efficient route to conjugated anomeric dienes or aldehydes based on the reaction of aldono-1,4- and aldono-1,5-lactones (1, 62) with allylmagnesium chloride (Scheme 19), giving allyl hemiacetals (e.g., 63a, b). Hemiacetal can be dehydrated [e.g., with (CF3C0)20] to produce dienes 64a, b, or ozonolyzed (e.g., to give 65). 

A variety of functional groups like benzyl ethers, tetrahydropyranyl ether, benzoate, (f-butyldiphenylsiloxy) ether, hemiacetal, lactone and aldehyde remain intact under these reaction conditions. 

The functions of flavoprotein enzymes are numerous and diversified.151-1533 A few of them are shown in Table 15-2 and are classified there as follows (A) oxidation of hemiacetals to lactones, (B) oxidation of alcohols to aldehydes or ketones, (C) oxidation of amines to imines, (D) oxidation of carbonyl compounds or carboxylic acids to a,(3-unsaturated compounds,... 

The synthesis of 11 -oxaprostaglandins from o-glucose uses the typical reactions of gl cofuranose diacetonide outlined on p. 267. Reduction of the hemiacetal group is achieved a thioacetal. The carbon chains are introduced by Wittig reactions on the aldehyde grou which are liberated by periodate oxidation and lactone reduction (S. Hanessian, 1979 G. Lourens, 1973). 

Reduction of lactone 5 results in lactol 6, a cyclic hemiacetal. Thus, the ester function is reduced only to the level of an aldehyde. 

Oxidation of hemiacetals.1 Pyridinium dichromate in DMF effects a novel oxidative cyclization of the aldehyde 1 to the macrocyclic lactone verrucarin T (2a). The conversion is believed to involve cyclization to a hemiacetal (2b) followed by oxidation to 2a. Manganese dioxide does not oxidize 1, and a variety of other oxidants attack the dienic ester side chain. 

The first step of this domino reaction opens the lactone 15 by reaction with potassium carbonate in methanol leading to hemiacetal 49. This is not stable under the reaction conditions and decomposes yielding aldehyde 50 and PMBOH 35 (see formation of acetal 40 described above). 

Simple iridoids are volatile iridoids of which the best known is the cat-exciting nepetalactone (C5 C50L) from Nepeta cataria (catnip) (Lamiaceae). The lactone nepetalactone, the hemiacetal neomatatabiol (G51G50H), iridodiol (in the ring opened bi-aldehyde... 

In DERA reactions, where acetaldehyde is the donor, products are also themselves aldehydes. In certain cases a second aldol reaction will proceed until a product has been formed that can cyclize to a stable hemiacetal.71 For example, when a-substituted aldehydes were used, containing functionality that could not cyclize to a hemiacetal after the first aldol reaction, these products reacted with a second molecule of acetaldehyde to form 2,4-dideoxyhexoses, which then cyclized to a hemiacetal, preventing further reaction. Oxidation of these materials to the corresponding lactone, provided a rapid entry to the mevinic acids and compactins (Scheme 5.43). Similar sequential aldol reactions have been studied, where two enzyme systems have been employed72 (Scheme 5.44). The synthesis of 5-deoxy ketoses with three substitutents in the axial position was accomplished by the application of DERA and RAMA in one-pot (Scheme 5.44). The long reaction time required for the formation of these thermodynamically less stable products, results in some breakdown of the normally observed stereoselectivity of the DERA and FDP aldolases. In a two-pot procedure, DERA and NeuAc aldolase have... 

The stereoselective allylation of aldehydes was reported to proceed with allyltrifluorosilanes in the presence of (S)-proline. The reaction involves pentacoordinate silicate intermediates. Optical yields up to 30% are achieved in the copper-catalyzed ally lie ace-toxylation of cyclohexene with (S)-proline as a chiral ligand. The intramolecular asymmetric palladium-catalyzed allylation of aldehydes, including allylating functionality in the molecules, via chiral enamines prepared from (5)-proline esters has been reported (eq 15). The most promising result was reached with the (S)-proline allyl ester derivative (36). Upon treatment with Tetrakis(triphenylphosphine)palladium(0) and PPh3 in THF, the chiral enamine (36) undergoes an intramolecular allylation to afford an a-allyl hemiacetal (37). After an oxidation step the optically active lactones (38) with up to 84% ee were isolated in high chemical yields. The same authors have also reported sucessful palladium-catalyzed asymmetric allylations of chiral allylic (S)-proline ester enamines" and amides with enantiomeric excesses up to 100%. 

A related oxidation reaction is catalyzed by glucose-6-phosphate dehydrogenase, the enzyme that originally attracted Warburg s attention and led to the discovery of NADP. The subsfrafe, the hemiacetal ring form of glucose, is oxidized fo a lactone which is then hydrolyzed to 6-phosphogluconate (Eq. 15-10). This oxidation of an aldehyde to a carboxylic acid is not linked directly to ATP synthesis as in Fig. 15-6. 

The reduction of esters to aldehydes generally works best when alkoxy or amino functionality is in close proximity to the ester group, as in a- or -alkoxy esters. A neighboring alkoxy group will stabilize the tetrahedral intermediate through chelation and prevent overreduction. DIBAL-H-mediated mono-reduction of lactones delivers the corresponding lactols (hemiacetals). ... 

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