Subject glycoside synthesis

The third theme is concerned with the chemical synthesis of O- and Af-glycosy compounds, and of oligosaccharides, and is the subject of ten chapters. The most widely used methods for glycoside synthesis are discussed, together with the inclusion of concept tually new approaches to anmneric activation and glycoside synthesis. 

The use of free radical chemistry at the anomeric center to produce carhon-carhon bonds, especially in an intramolecular fashion, remains a popular method for C-glycoside synthesis. A review entitled C-Glycosidation Technology with Free Radical Reactions appeared in early 1998, and the reader is referred to that somce [2] as well as to the more traditional ones for complete overviews on the subject. Again, the coverage here focuses on the most recent developments. 

C-glycosides Vasella has reviewed his work on glycosylidene carbenes which is of relevance to the subject, and the use of glycosyl carbanions in C-glycoside synthesis has also been surveyed. ... 

A recently developed application of the Ramberg-Backlund reaction is the synthesis of C-glycosides. The required thioethers can be prepared easily by exchange with a thiol. The application of the Ramberg-Backlund conditions then leads to an exocyclic vinyl ether that can be reduced to the C-nucleoside.95 Entries 3 and 4 in Scheme 10.6 are examples. The vinyl ether group can also be transformed in other ways. In the synthesis of partial structures of the antibiotic altromycin, the vinyl ether product was subjected to diastereoselective hydroboration. 

In this respect it is interesting to note that the tandem aldolization technique proved amenable also to the synthesis of a first C-glycosidic aza sugar (Scheme 2.2.5.19) [29, 36]. A rather simple dihydroxylated azido dialdehyde was generated from racemic azidocyclohexene 60 and subjected to FruA catalysis. The latter effected a smooth tandem addition to provide a diastereoisomerically pure bispyranoid azido C-disaccharide 61, from which the pyrrolidine-type aza sugar 62 was... 

Martin et al. (289) utilized the chiral bicyclic lactone 88 for a total synthesis of (+)-phyllanthocin (Scheme 6.62). Cycloaddition of 88 to acetonitrile oxide, generated in situ from hydroximoyl chloride (89), furnished cycloadduct 90 in 45% yield together with other regio- and stereoisomers. After several steps, methyl glycoside (91) could be obtained. From this, reduction-hydrolysis gave the aldol that was subjected to acid-catalyzed spiroacetalization to produce spiroketal (92), and eventually (+)-phyllanthocin (93) after two additional steps (289). The... 

From a strictly chemical point of view, the synthesis of glycosides still presents a formidable challenge to synthetic chemists in spite of major advances in the area [1], Unlike peptidic bonds, the formation of the glycosidic linkage is subject to various factors that include, among others, electronic, stereoelectronic, conformational, substituent, and reactivity effects generally associated with incipient oxocarbenium ions derived from carbohydrates. 

Bacillus circulans P-galactosidase prefers 1,4-glycosidic bond formation and ha been used in the large-scale synthesis of IV-acetyllactosamine (7). Coupled with a oi2,6-sialyltransferase, the disaccharide 7 was converted to the sialyldisaccharide, which is nc longer subject to the glycosidase-catalyzed hydrolysis, thus improving the yield (set experimental section) [35]. 

Deoxy sugars are of wide occurrence as components of nucleic acids, natural glycosides, and antibiotics, and they were the subject of an earlier article by Hanessian in Volume 21. Here, de Lederkremer and Marino (Buenos Aires) provide a detailed update on the distribution of deoxy sugars in natural products, along with a survey of methods for their synthesis. 

The de novo discovery synthesis of capecitabine (1) was reported by the Nippon Roche Research Center scientists9,19 and was followed up with a preparation invented by a team at the Hoffinann-La Roche laboratories in New Jersey for the conversion to 1 from 5 -DFCR (10).2° In the first route, 5-fluorocytosine (15) was mono-silated using one equivalent of hexamethyldisilazane in toluene at 100 °C followed by stannic chloride-catalyzed glycosidation with known 5-deoxy-l,2,3-tri-0-acetyl-p-D-ribofuranoside (17) in ice-cooled methylene chloride. While this procedure provided the 2, 3 -di-0-acetyl 5-fluorocytidine 18 in 76% yield on a 25-g scale, an alternative method was also devised using in situ-generated trimethylsilyl iodide in acetonitrile at 0°C to provide a 49% yield of 18 on smaller scale. Acylation of the N -amino group of the bis-protected 5 -DFCR derivative was accomplished by the slow addition of two equivalents of -pentyl chloroformate to a solution of 18 in a mixture of pyridine and methylene chloride at -20 °C, followed by a quench with methanol at room temperature to provide the penultimate intermediate 19 on 800-g scale. The yield of intermediate 19 was assumed to be quantitative and was subjected to the final deprotection step, with only a trituration to... 

The synthesis of this substance was also effected by F. Smith.2 Methyl 6-trityl-a-D-galactopyranoside, in acetone solution, was treated six times with dimethyl sulphate and sodium hydroxide solution. The imperfectly methylated material thus obtained was then subjected to two treatments with methyl iodide and silver oxide. The necessity for so many treatments with methylating reagents emphasizes the difficulty of etherifying a glycoside substituted by the trityl radical in position 6. Subsequent to removal of the trityl radical, the methyl 2,3,4-trimethyl-(33) J. S. D. Bacon, D. J. Bell and J. Lorber, J. Chem. Soc., 1147 (1940). 

---