Carbohydrates, acidic derivatives preparation

M.-J. Kim, W. J. Hennen, H. M. Sweers, and C.-H. Wong, Enzymes in carbohydrate synthesis 79-Acetylneuraminic acid aldolase catalyzed reactions and preparation of 7V-aceiyl-2-deoxy-D-neuraminic acid derivatives, J. Am. Chem. Soc. 770 6481 (1988). 

Most work on side-chain reactions deals with carbohydrate chemistry in connection with the preparation of nucleoside analogues. In the more simple case of the hydroxymethyl derivative (208), thionyl chloride treatment gives the corresponding chloromethyl derivative and the chlorine is replaced by sulfur nucleophiles in the preparation of dithiophosphoric acid derivatives (209) (76HCA1593). 

The use of chiral 1-oxa-l,3-butadienes for the stereoselective preparation of carbohydrates has also been investigated by Schmidt et al. [479]. The elegant syntheses of N-acetyl-/J-D-neuraminic acid derivatives are an impressive result of these studies [480]. 

Howwjanz discovered that a large number of carbohydrates and poly-hydric alcohols can combine with carbon dioxide in the presence of excess milk of lime to form unstable acid carbonate salts, R—0—CO—0 M . Stable, neutral esters of carbonic acid with carbohydrates were first prepared in 1912 by Hochstetter, who patented a process involving reaction with diphenyl carbonate at about 130°. However, not one of the examples cited—derivatives of D-glucose, sucrose, D-mannitol, and starch—was completely characterized and, possibly on account of the rather drastic conditions used, Hochstetter s method has not received attention from later workers. 

Mukaiyama and coworkers have pioneered many routes to the total syntheses of rare carbohydrates such as the 2-amino-2-deoxypentoses [75]. In 1982, they reported that the potassium enolate derived from the magnesium salt of the (/ )-atrolactic acid derivative 85 adds to 2,3-0-isopropylidene-D-glyceraldehyde in a highly stereoselective manner giving, after alcohol protection, imine hydrolysis and amine protection, the D-arabinopentoate derivative 86 (Scheme 13.35). Further elaboration leads to 2-acetamido-2-deoxy-D-arabinose 87. In a similar fashion, starting from (5 )-atrolactic acid, 2-acetamido-2-deoxy-D-ribose 88 was prepared [76]. 

The brominated sugars are usually quite stable and can be useful for a variety of purposes [151]. Substitution of bromine with deuterium can be used for preparation of labeled carbohydrates, while substitution with hydrogen sometimes can be used for inverting the stereochemistry. Noteworthy is the conversion of D-glucuronic acid derivative 61 into the corre-... 

The chiral pool has provided the backbone of many products. Carbohydrates [17] and amino acids are often used because of the high degree of functionality and the ready availability of these compounds from natural sources. Enalapril maleate contains the dipeptide L-alanyl-L-proline (Figure 16.1a) [18]. Aztreonam is derived from L-threonine (Figure 16.1b) [19].The chiral ester 2 was prepared from an amino acid derivative 1 (Figure 16.1c) [20]. In this transformation the original chiral center from L-cysteine was destroyed, similar to self-immolative processes [21]. 

In 1995 Nicolaou and coworkers initiated a renaissance in the construction of sugar amino acid conjugates with their synthesis of carbonucleotoids [49]. Although they did not prepare amide-linked carbohydrates, they did introduce the term carbopep-toid to designate such materials. Shortly thereafter, a number of papers directed toward the synthesis of carbopeptoids appeared. One of the earliest was reported by Wessel et al., who used nor-muramic acid derivatives and condensed them in solution by means of 2-chloro-4,6-dimethoxy-l,3,5-triazine (CDMT) in DMF to construct a tetramer (Fig. 27). 

Kunz and Pfrengle [96] introduced the formation of a-amino-acid derivatives by U-4CR with chiral O-acylated amino-carbohydrates like 2i and formic acid 3f. Usually, their products are formed relatively stereoselectively, and generally in good yield. It seems that the use of formic acid 3f proceeds in the U-4CRs better than do other acid components of 3A, as its amine components like 2i are sterically hindered. The essential disadvantage of the products 18p is that subsequent cleavage of its C-N bond into 33 and 34 can be accomplished only by strong acids such as HC1. Thus, it is doubtful if delicate chiral a-amino acid derivatives or peptides can be prepared successfully in this manner. 

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