Aldose Derivatives

1 Total Synthesis of d- and l-Glyceraldehyde and Other C-3 Aldose Derivatives 

EtOH/H+ X XOOH 2- PhCHO 0. xxCOOEt O COOEt LiAIH4 AICI3 HO— pOH 

HOOC Y OH (S,S)-tartaric acid TsOH, PhH reflux CH2CI2 (91%) —OBn —OH 

The synthesis of 3-0-methyl-D-glyceraldehyde starts with D-fructose [52]. The preparation of 2-0-methyl-D-glyceraldehyde and 2-0-benzyl-D-glyceraldehyde (R)-25 starts from D-mannitol [53]. 

SCHEME 13.21 Desymmetrization of meso-diacetate by lipase-catalyzed hydrolysis synthesis of C3-alditol derivatives. 

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Fig. 1. The family of D-aldoses derive from D-glyceraldehyde by chain extension at the carbonyl carbon atom.

Commercial A -acetylneuraminic acid aldolase from Clostridium perfringens (NeuAcA EC 4.1.3.3) catalyzes the addition of pyruvate to A-acetyl-D-mannosamine. A number of sialic acid related carbohydrates are obtained with the natural substrate22"24 or via replacement by aldose derivatives containing modifications at positions C-2, -4, or -6 (Table 4)22,23,25 26. Generally, a high level of asymmetric induction is retained, with the exception of D-arabinose (epimeric at C-3) where stereorandom product formation occurs 25 2t The unfavorable equilibrium constant requires that the reaction must be driven forward by using an excess of one of the components in order to achieve satisfactory conversion (preferably 7-10 equivalents of pyruvate, for economic reasons). 

The name of an aldose derivative in which the aldehyde group has been replaced by a terminal CH3 group is derived from that of the appropriate alditol (see 2-Carb-19) by use of the prefix deoxy- . 

D-aldoses derived from, 4 698 D-Glyceraldehyde 3-phosphate, 4 711 Glycerides... 

H. Chikashita, T. Nikaya, and K. Itoh,.Iterative and stereoselective one-carbon homologation of 1,2-O-cyclohexylidene-D-glyceraldehyde to aldose derivatives by employing 2-lithio-l,3-dithiane as a formyl anion equivalent, Nat. Product Lett. 2 183 (1993). 

One cyclization procedure that depends on this approach has been described in an earlier section. A further method that affords double activation of a methylene group at C-6 of aldose derivatives, and simultaneous release of an aldehydic group, leads to C-6- to C-l-bonding under extremely mild conditions and is compatible with the presence of most O-protecting groups (Scheme 11). For this reason, and because the cyclization step is normally very efficient and stereoselective, this strategy has been used extensively, ft... 

Some other mono-O-sulfonylated-aldose derivatives to which the iodination reaction has since been successfully applied (either prepara-tively or diagnostically, or both) are listed in Table III. The yields given therein are those recorded by the authors, and have not been recalculated. Where the yield approaches the theoretical, there is seldom any indication that the same yield might not have resulted at a lower temperature or after a shorter reaction-time, or both. Low yields might, in some instances, be attributable to poor experimental technique. However, despite its deficiencies, Table III contains sufficient information to warrant a few conclusions, some of which are to be found scattered through the literature. 

Compounds of this category are vinyl ethers having double bonds between C-l and C-2 of pyranoid or furanoid aldose derivatives. Analogues with exocyclic C-l-C-2 double bonds in cyclic 2-ketoses are sometimes referred to as evo-glycals and are covered briefly in Section IV.3 isomers with C-2-C-3 unsaturation in 2-ketoses can be considered as C-l-substituted glycals and are referred to in Section II.3.a. Together the glycals and their derivatives constitute the most useful set of unsaturated carbohydrate derivatives for application in synthesis. 

Methods for the chemical synthesis of glycuronic acids include (i) reduction of the monolactones of aldaric acids, (ii) oxidation of the primary alcoholic group of aldose derivatives, (iii) oxidative degradation procedures, (iv) chain-extension reactions on dialdoses, and (v) epimerization reactions. 

The decarbonylation reaction is not confined to aldehydes, but also embraces those compounds that have aldehyde tautomers. Thus, both carbohydrates and allylic alcohols can be decarbonylated. When glucose is allowed to react with frani -[RhCl(CO)(PPh3)2] in A -methylpyrrolidin-2-one, decarbonylation occurs and arabinitol is formed with retention of configuration. The decarbonylation of fructose to arabinitol is complicated by the simultaneous dehydration to furfinyl alcohol, which is the major product. Analogous reactions occur with lower carbohydrates in the limit, glycolaldehyde is decarbonylated to methanol. Aldose derivatives can also be converted to their C i analogues, but the yields are only about half of those obtained with the parent aldoses. Disaccharides usually give better yields. 

Reaction of aldose derivatives with dimethyl(diazomethyl)phosphonate (382) generated in situ by methanolysis of dimethyl(l-diazo-2-oxopropyl)phosphonate leading to gluco-l-ynitol derivatives (383) has been described. This one-pot synthesis tolerates free hydroxyl groups. ... 

Tadano, K, Maeda, H, Hoshino, M, limura, Y, Suami, T, A new transformation of aldose derived synthons to pseudo-hexopyranose or pseudo-pentofuranose derivatives, Chem. Lett., 1081-1084, 1986. 

Total Synthesis of D- and L-Glyceraldehyde and other C-3 Aldose Derivatives... 883... 

Table 34.1 Names of Aldose Derivatives Type of Compound Type Name Examples of Specific Names...

Synthesis of the 3,4,6-trimethyl ether of 2-deoxy-2-methylamino-n-gluconic acid was carried out along lines similar to those of the synthesis of the 3,6-dimethyl ether. By the addition of methylamine and hydrogen cyanide to 2,3,5-tri-O-methyl-n-arabinose, followed by hydrolysis, only one compound was formed, and this was related to n-glucosamine on the basis of its optical rotation. An attempt to obtain the aldose derivative by reduction with sodium amalgam was not successful, probably because of the impossibility of 5-lactone formation. 

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