Glycosyl synthon, synthesis

Another method for synthesis of useful derivatives of L-acosamine and L-daunosamine from rhamnal 23 was based on addition of chlorosulfonyl isocyanate to 2,3-unsaturated pyranosides 73 [66,67]. Since the anomeric alkyl substituent in this reaction ends up as the carbamate ester, aUyl glycoside securing easy deprotection was chosen for elaborating this reaction into large laboratory scale technical process. Method development for acosam-inal derivative 74 involved multiparameter optimization of the isocyanate addition step by exploration of the reaction response surface. The final daunosaminyl glycosylation synthon 76 was obtained in overall 35% yield (Scheme 12) [68]. 

Recent developments in the enzymatic synthesis of carbohydrates can be classified into four approaches 1) asymmetric C-C bond formation catalyzed by aldolases (1-10 2) enzymatic synthesis of carbohydrate synthons (loll) 3) asymmetric glycosidic formation catalyzed by glycosidases (12.-17) and glycosyl transferases (18-23.) and 4) regioselective transformations of sugars and derivatives (24-25). These enzymatic transformations are stereoselective and carried out under mild conditions with minimum protection of functional groups. They hold promise in preparative carbohydrate synthesis. In connection with this book, we focus on the first two approaches. 

For the next stage of the stepwise synthesis, the preparation of the trimer of I, VIII was converted into the glycosyl bromide IX which was condensed with the aglycone synthon VII in a similar manner to give the protected nonasaccharide X (yield 57%). After removal of the protecting groups, the trimer of the repeating unit I, compound XI was obtained. 

A derivative of L-oliose (54L) suitable for glycosylation was obtained from L-fucose169 using the Barton deoxygenation method for introduction of the 2-deoxy function. Another approach for the synthesis of L-oleosyl synthons started from the 3,4-di-D-acetyl L-fucal (71), readily converted into the corresponding chloride (Scheme 24).138 This method was used for the synthesis of dTDP-p-L-oliose, a glycosyl donor in the construction of aclacinomycin A (72). 

Carbohydrate-derived homoallylamines have been demonstrated as being useful chiral synthons for the stereoselective synthesis of P-amino acids. With allyltribu-tylstannane or allyltrimethylsilane as the nucleophiles, glycosyl imines form homoallylamines with high efficiency [29-31]. Promoted by SnCl4, the nucleophile al-lyltributylstannane attacks from the stoically less hindered side. 

The chiral piperidinones 46 formed by the reaction between Danishefsky s diene and the glycosyl imines are valuable synthons for the synthesis of higher substituted piperidine derivatives. 2,6-Disubstituted piperidinones 49 are obtained by addition of organocuprates complexes with boron trifluoride [53]. The reaction pathway is illustrated in Scheme 30. 

Inversion of configuration (cf Epimerization) of alcohols (Mitsunobu reaction), 160-161, 286 of ally lie acetates with Pd, 27, 164 of allylpalladium with d-synthons, 27, 264 of alkyl halides or sulfonates by 1,3-dithiane anions, 22 by organylcuprates, 36 by tetracarbonylferrate<2 -X 46-47 in triorganylborane rearr., 37-38 of glycosides with free 2-OH by DAST, 272 of glycosyl halides, 271 of oxiranes by 1-alkync anions, 64, 204 by enolate type anions, 63-64 by internal alcoholate addition, 265 Inversion-esterification of alcohols, 160-161, 286 Inverted DNA , 345-346 Iodide, hydrogen porphyrin synthesis with, 255 Iodine = diiodine (Ij) ... 

The various parts of Chapter 3 describe the preparation of polyene synthons and the synthesis of different groups of carotenoids, the partial synthesis of carotenoid glycosides, glycosyl esters and sulphates. Technical synthesis and the synthesis of isotopically labelled carotenoids are also covered. 

The most widely used synthons for the synthesis of thiooligosaccharides are the 1-thioglycoses and their synthesis has been widely studied. Approaches for the synthesis of 1,2-tra -thioglycoses include nucleophilic sulfur substitutions at the anomeric center of the glycosyl halides with either pscwdo-thiourea derivatives or other thionucleophiles [9, 10]. More recently, phase-transfer catalysis [11] and mild Lewis acid catalysed glycosidation of peracetylated sugars with thioacetic acid [12] have been applied. 

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