L-Aldoses

Scheme 21 Synthesis of L-aldoses from D-glucono-1,5-lactone...

After repeated cyanhydrin reactions, four tetroses will provide a total of eight pentoses (each tet-rose provides a pair of new diastereomers with one more chiral center), which can then yield sixteen stereoisomeric hexoses. The compounds derived from D-glyceraldehyde are designated as D-aldoses and those from L-glyceraldehyde as L-aldoses. 

As shown for the aldotetroses an aldose belongs to the d or the l series accord mg to the configuration of the chirality center farthest removed from the aldehyde func tion Individual names such as erythrose and threose specify the particular arrangement of chirality centers within the molecule relative to each other Optical activities cannot be determined directly from the d and l prefixes As if furns ouf bofh d eryfhrose and D fhreose are levorofafory buf d glyceraldehyde is dexfrorofafory... 

Up to this point all our attention has been directed toward aldoses carbohydrates hav ing an aldehyde function in their open chain form Aldoses are more common than ketoses and their role m biological processes has been more thoroughly studied Nev ertheless a large number of ketoses are known and several of them are pivotal inter mediates m carbohydrate biosynthesis and metabolism Examples of some ketoses include d nbulose l xylulose and d fructose... 

The reaction is used for the chain extension of aldoses in the synthesis of new or unusual sugars In this case the starting material l arabinose is an abundant natural product and possesses the correct configurations at its three chirality centers for elaboration to the relatively rare l enantiomers of glucose and mannose After cyanohydrin formation the cyano groups are converted to aldehyde functions by hydrogenation m aqueous solution Under these conditions —C=N is reduced to —CH=NH and hydrolyzes rapidly to —CH=0 Use of a poisoned palladium on barium sulfate catalyst prevents further reduction to the alditols... 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

Fischer projections and, 977-978 glycosides and, 989-990 l- 4 links in, 997-998 origin of name. 973 photosynthesis of, 973-974 see also Aldose, Monosaccharide vaccines from, 1004-1005 Carbon, ground-state electron configuration of, 6... 

Stacey started research in an inspiring and stimulating atmosphere that he strove to maintain, add to, and develop when it became his turn to lead the department. His earliest research was with Haworth and his key partner E. L. Hirst [Adv. Carbohydr. Chem. Biochem., 35 (1978) 1 -29] on aspects of the chemistry of glucoheptose. His first publication with them in 1931 was entitled Walden Inversion in the a-Glucoheptose Series, followed in the next year by a report on the methylation of monocarboxylic acids derived from aldoses and the structure of pentamethyl a-gluco-heptonolactone. He found this to be a difficult project because, initially, he could not crystallize his stock of glucoheptose. Then, as later, he found crystallization to be a challenging problem. 

Methylation of Monocarboxylic Acids Derived from Aldoses. Structure of Pentamethyl a-Gluco-heptono-y-lactone, W. N. Haworth, E. L. Hirst, and M. Stacey, J. Chem. Soc., (1932) 2481-2485. 

Chart I. Trivial names (with recommended three-letter abbreviations in parentheses) and structures (in the aldehydic, acyclic form) of the aldoses with three to six carbon atoms. Only the D-forms are shown the L-forms are the mirror images. The chains of chiral atoms delineated in bold face correspond to the configurational prefixes given in italics below the names... 

Mirror images a-o-glucopyranose-4Ci (upper) and a-L-glucopyranose-1C4 (lower) 2-Carb-8. Aldoses 2-Carb-8.1. Trivial names... 

Deoxy-3-[(l/Z,2S)-l,2-dihydroxy-3-oxopropyl]-D-gZycer0-D-aZfr0-heptopyranose or 3-deoxy-3-(D-f/jreo-1,2-dihydroxy-3-oxopropyl)-D-g/ycero-D-a/rro-heptopyranose (not the alternative open-chain six-carbon dialdose or eight-carbon aldose, cf. 2)... 

Rastelli G, Ferrari AM, Constantino L, Gamberini MC. Discovery of new inhibitors of aldose reductase from molecular docking and database screening. Bioorg Med Chem 2002 10 1437-50. 

Through extensive screening of compounds, " " " it was revealed that this enzyme accepts a very wide range of substrates. In addition to phosphorylated aldose, which are the native substrate, non-phosphorylated aldose, simple aliphatic, aromatic, heterocyclic and functionalized aldehydes, even with an increased hydropho-bicity, work as substrates. The stereochemical course has been elucidated in Fig. 18. The hydroxyl group on the 2-position of the aldehyde is very important and 2-deoxygenated aldehydes were rather weak substrates. The substrates with d-configuration at the 2-position have a stronger affinity to TKase than L-form. 

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