Carbohydrates diastereomers

With the new very high resolution NMR spectra, it should be a simple matter to assign configurations to other difficult cyclitols or carbohydrates, for example, the numerous still undiscovered isomers of 6-bromo, 6-chloro, and 6-iodoquercitol (20 diastereomers predicted for each). 

The polymerization of several different protected monomers was executed with the molybdenum initiator. Two types of norbornene templates were generated as mixtures of diastereomers one class possessed a single saccharide substituent attached through either an endo or exo ester group, and the other was equipped with two carbohydrate residues appended to the bicyclic scaffold... 

In principle, mass spectrometry is not suitable to differentiate enantiomers. However, mass spectrometry is able to distinguish between diastereomers and has been applied to stereochemical problems in different areas of chemistry. In the field of chiral cluster chemistry, mass spectrometry, sometimes in combination with chiral chromatography, has been extensively applied to studies of proton- and metal-bound clusters, self-recognition processes, cyclodextrin and crown ethers inclusion complexes, carbohydrate complexes, and others. Several excellent reviews on this topic are nowadays available. A survey of the most relevant examples will be given in this section. Most of the studies was based on ion abundance analysis, often coupled with MIKE and CID ion fragmentation on MS " and FT-ICR mass spectrometric instruments, using Cl, MALDI, FAB, and ESI, and atmospheric pressure ionization (API) methods. 

A useful application of the chemistry shown in Scheme 83 is the synthesis of branched-chain functionalized carbohydrates. For this purpose two epoxides 261 and 262 derived from D-glucose and 263 derived from D-fructose were prepared following reported methodologies, and were submitted to a DTBB-catalyzed lithiation as described above in Scheme 83. The expected intermediates 264-266 and final products 267-269 were prepared in a regio- and stereoselective manner in 15- 95% yield" Also here, the use of a prochiral electrophile gave equimolecular amounts of both diastereomers. 

Since first proposed by Bax et al. [4, 5] and Kessler et al. [6], the ID TOCSY technique has been gaining popularity among NMR spectroscopists as well as practicing chemists. The ID TOCSY technique has been applied to the assignment of peptides [6, 12, 19-21], carbohydrates [22-34], steroids and alkaloids [35-43], carotenoids [44] and mixtures (of reaction products, isomers and diastereomers) [22b, 45 9]. The references cited here may represent only a small fraction of the work in the literature reporting the use of the ID TOCSY technique. 

The most widely applicable method of optical resolution utilizes a chiral auxiliary, which is taken from either the chiral pool 14 (carbohydrates, terpenes, amino acids etc.) or obtained by previous optical resolution. The auxiliary A, in an optically pure form, combines with the racemic substrate S to form two diastereomers p and n, respectively. 

An asymmetric C-C coupling, one of the most important and challenging problems in synthetic organic chemistry, seems to be most appropriate for the creation of a complete set of diastereomers because of the applicability of a convergent, combinatorial strategy [38-40]. In Nature, such reactions are facilitated by lyases which catalyze the (usually reversible) addition of carbo-nucleophiles to C=0 double bonds, in a manner mechanistically most often categorized as aldol and Claisen additions or acyloin reactions [41], The most frequent reaction type is the aldol reaction, and some 30 lyases of the aldol type ( aldolases ) have been identified so far [42], of which the majority are involved in carbohydrate, amino acid, or hydroxy acid metabolism. This review will focus on the current state of development of this type of enzyme and will outline the scope and limitations for their preparative application in asymmetric synthesis. 

However, a reversal of the diastereofacial selectivity may arise when the substrate has, in a or f) position of the side chain, a group prone to complexation with the Lewis acid. Then, the use of bidentate Lewis acids such as MgBr2, TiCU or ZnCL allows the reaction to proceed under a chelation control model, providing preferentially the syn adduct for a 1,4-chelation and the anti adduct for a 1,5-chelation. This was exploited in the stereoselective synthesis of both diastereomers, simply by changing the chelation conditions on the substrate18. An impressive amount of work was done with various a-alkoxy aldehydes19-23 as a route to carbohydrate chemistry. Similarly, a-amino aldehydes were used as substrates for /3-amino alcohol synthesis24,25. 

Annulene (Section 16.10) A name sometimes given to rings that contain alternating single and double bonds in a single Lewis structure. Anomers (Section 25.3) Diastereomers that are formed by cyclization of a carbohydrate with differing configurations at the new stereocenter. 

C-Alkyl glycosides are useful carbohydrate mimetics, commonly employed as enzyme inhibitors. The formation of various C-alkyl glycosides was evaluated with phosphates 9 and 12 (Table 3). Mannosyl phosphate 9 was activated with TMSOTf and coupled to allyltrimethylsilane to provide a-allyl glycoside 2 (18) in excellent yield (93%). Coupling of 9 to the cyclopentanone derived trimethylsilyl enol ether 35 afforded 34 as a mixture of diastereomers in 84%... 

Classification of Carbohydrates 1102 23-3 Monosaccharides 1103 23-4 Erythro andThreo Diastereomers 1106 23-5 Epimers 1107... 

The intramolecular conjugate addition of a nucleophilic oxygen to a chiral precursor allows tctrahydro-2//-pyrans to be prepared with high stereochemical control. Treatment of the carbohydrate derivative 1 with methanolic potassium hydroxide immediately gives an equimolar, inseparable mixture of products, however, by successive equilibration, there is formation of the 2,6-cw-disubstituted diastereomer 2 in which the less slcrically encumbered equatorial orientation of the methoxycarbonylmethyl group is reached88. 

One of the following molecules (a)-(d) is n-erytlirose 4-phosphale, an intermediate in the Calvin photosynthetic cycle by which plants incorporate CO2 into carbohydrates. If o-erythrose 4-phosphate has R stereochemistry at both chirality centers, which of the structures is it Which of the remaining three structures is the enantiomer of o-erythrose 4-phosphate, and which are diastereomers ... 

Coleman (57) synthesized the anhydride of acid (R)-[9] and used it to determine the enantiomeric purity of oxfenicine [(S)-(+)-p-hydroxy-phenylglycine), a therapeutic agent that promotes carbohydrate oxidation. The anhydride had to be used in the derivatization since the use of add chloride [8] led to racemization of the drug due to the presence of the required base catalyst. The diastereomers were separated by silica gel LC and detected at 254 nm (57). 

Copper and rhodium complexes catalyze the reaction of alkenes with diazoacetate to give alkyl cyclopropanecarboxylates [13]. In the presence of Cu(acac)2, the reaction of carbohydrate enol ether 20 with methyl diazoacetate afforded a 1 4 mixture of cis- and frani-cyclopropanes 21 and 22 (c -product 21 was obtained with 95% de). When the reaction was catalyzed by CuOTf in the presence of hgand 23, the tranj -product 22 was obtained with 60% de (Scheme 10.4). The absolute configuration of the major diastereomer was not given [19]. 

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