Glyceraldehyde acetal

HC CH(0H) CH20H. optically active. D-glyceraldehyde is a colourless syrup. May be prepared by mild oxidation of glycerol or by hydrolysis of glyceraldehyde acetal (prepared by oxidation of acrolein acetol). DL-glyceraldehyde forms colourless dimers, m.p. IBS-S C. Converted to methylglyoxal by warm dilute sulphuric acid. The enantiomers... 

Acetals are readily hydrolyzed by dilute mineral acids however, the yields are not always satisfactory. These substances are not affected by alkaline reagents. The sensitive JZ-glyceraldehyde acetal is converted to its aldehyde in 80% yield by the action of dilute sulfuric acid under mild conditions. Other procedures are illustrated by the treatment of acetals which are formed by the interaction of Grignard reagents and orthoformic esters (method 165). 

Various kinds of chiral acyclic nitrones have been devised, and they have been used extensively in 1,3-dipolar cycloaddition reactions, which are documented in recent reviews.63 Typical chiral acyclic nitrones that have been used in asymmetric cycloadditions are illustrated in Scheme 8.15. Several recent applications of these chiral nitrones to organic synthesis are presented here. For example, the addition of the sodium enolate of methyl acetate to IV-benzyl nitrone derived from D-glyceraldehyde affords the 3-substituted isoxazolin-5-one with a high syn selectivity. Further elaboration leads to the preparation of the isoxazolidine nucleoside analog in enantiomerically pure form (Eq. 8.52).78... 

The reaction of O-methyl-O-tert-butyldimethylsilyl ketene acetal with N-benzyl- and A-methyl-2,3-O-Mopropylidene D-glyceraldehyde nitrones (292), in the presence of boron trifluoride etherate, affords the corresponding isoxazolidine-5-ones in high yields. These compounds were successfully applied as key intermediates in the synthesis of isoxazolidinyl nucleosides of the L-series (Scheme 2.177) (638). 

Optically pure glyceraldehyde acetonides are widely used in the synthesis of enantiomerically pure compounds (EPC synthesis).1 2 3 4 5 Whereas D-(R)-glyceraldehyde acetonide is easily obtained from the inexpensive D-mannitol,6 7 there are only a limited number of practical syntheses of the enantiomeric L-(S)-glyceraldehyde acetonide.8 9 Difficulties arise from different sources 1) availability of the starting material diisopropylidene-L-mannitol 2) length of the synthesis 10 3) nature of the reactants used mercury acetate, mercaptans, lead tetraacetate, ozone at -78°C, 4) moderate yields.11 14... 

D-Glyceraldehyde (usually in the form of its 2,3-isopropylidene acetal 638) has been employed several times for the synthesis of various sugars. Although such syntheses are, in the strict sense, beyond the scope of this article, those in which reactions other than the aldol type of reaction were used for chain extension are described. 

The aldehyde ferredoxin oxidoreductase from the hyperthermophile Pyrococcus furiosus was the first molybdopterin-dependent enzyme for which a three-dimensional structure became available.683,684 The tungstoenzyme resembles that of the related molybdo-enzyme (Fig. 16-31). A similar ferredoxin-dependent enzyme reduces glyceraldehyde-3-phosphate.685 Another member of the tungstoenzyme aldehyde oxidoreductase family is carboxylic acid reductase, an enzyme found in certain acetogenic clostridia. It is able to use reduced ferredoxin to convert unactivated carboxylic acids into aldehydes, even though E° for the acetaldehyde/acetate couple is -0.58 V.686... 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

The diol (43) obtained from dihydroxylation of acrolein benzene-1,2-dimethanol acetal (entry 11) is a masked glyceraldebyde and has the potential to be a very useful synthon. Although the enantiomeric purity of the crude diol formed in this reaction is 84% ee, one recrystallization from ethyl acetate improves it to 97% ee in 55% recovery yield. The masked glyceraldehyde 43 is converted via the tosylate 44 to the masked glycidaldehyde 45 in an overall yield of 85%. Both these masked aldehydes are superior to the free aldehydes in terms of handling ease, stability, and safety. The aldehydes can be released from the acetal under the mild conditions of catalytic hydrogenolysis [45]. 

This affords the L-acetal 10 via hypochlorite treatment of the intermediate 3,4-acetal of L-erythrose 9. The protected O-alkylidene glyceraldehydes are extremely flexible and can be converted into a plethora of other chiral synthons with a wide selection of uses using very standard chemical transformations (scheme 5). One major limitation for its use is the ease of racemization of the chiral center because of the ease of enolization of the aldehyde group. This is especially true even in the mildest of basic conditions. 

The common nonenolide core of ascidiatrienolide and the didemnilactones has been formed as shown in Scheme 5 (22). Specifically, a tin-mediated, ultrasound-promoted addition of allyl bromide to unprotected glyceraldehyde 37 furnished a mixture of the corresponding homoallyl alcohols 38 which were subjected to acetalization and esterification with 5-hexenoic acid under standard conditions. At that stage, the major jy/i-isomer 40 can be purified by flash chromatography. Exposure of this diene to a refluxing solution of the ruthenium... 

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