Activation of Glycals

With the success of the IDCP method in the formation of simple glycosides, the next logical step was to attempt the synthesis of a disaccharide. Beginning with 

6- tri-0-acetyl-2-deoxy-2-iodo-a-D-mannopyranoside (37) in moderate yield. Catalytic hydrogenation of 37 provided the expected 2,3,4,6-tetra-0-acetyl- 3-D-glucosyl-3,4,6-tri-0-acetyl-2-deoxy-a-D-arabwio-hexopyranoside (38). 

In a study of NIS-promoted additions to glycals it was noted that when the nu-cleophilicity of the alcohol was low, a competing reaction occurred whereby the succinimide anion itself acted as a nucleophile, attacking the anomeric carbon.76,77 

Thiem and Ossowski79 considered that the conformation of the starting glycal was critical to the configuration of the product obtained. It was reasoned that 45 

The mechanism of glycal addition was further examined by Horton and coworkers,86 who have used this method to form (7S,9S)-4-demethoxy-7-0-(2,6-dideoxy-2-iodo-a-L-mannopyranosyl)-adriamycinone87 and -daunomycinone,88 which are iodinated analogs of natural antitumor compounds. The nature of the solvent was found to be critical. In particular, they were able to generalize that in non-coordinating polar solvents, where no possibility for interaction with iodine exists—that is, no lone-pair interactions—the formation of the iodonium intermediate was irreversible, and the resultant stereochemistry reflects the electronic 

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Activation of glycals by selenylation was introduced by Sinay and coworkers [41] by the sequential addition of PhSeCl and the glycosyl acceptor. A two-step version of this activation with the isolation of the intermediate glycosyl acetate [596] has also been reported. 

The direct synthesis of fully functionalized sugars possessing amino or hydroxyl functions at C-2 has also been studied. Thus, activation of glycals by thianthrene-5-oxide 287 and Tf20, followed by treatment with an amide nucleophile and a glycosyl acceptor, led directly to various 2-acylamido glycosides 288 [610,611] (Scheme 4.59). 

Before starting any structural modulation, we first evaluated the effect of the C-9-C-10 unsaturation on antimalarial activity and ascertained that the presence of a CF3 group at C-10 could disfavor the protonation leading to oxonium 14, and hence the further gluc-uronidation (see Scheme 6.4). The antimalarial activities of glycals 10 and 18 have been assessed and compared (see Figure 6.3) [58], Whereas in vitro activities on P. falciparum... 

The galactosyl glycal 72 was bound to solid phase via a silyl ether linker. Epoxidation of the glycal using 2,2-dimethyldioxirane and subsequent electrophilic activation of the epoxide resulted in the glycosylation of 3,4-di-O-benzyl glucal 73. After acetylation of the product, the polymer-linked trisaccharide 74 was obtained. 

The haem peroxidases are a superfamily of enzymes which oxidise a broad range of structurally diverse substrates by using hydroperoxides as oxidants. For example, chloroperoxidase catalyses the regioselective and stereoselective haloge-nation of glycals, the enantioselective epoxidation of distributed alkenes and the stereoselective sulfoxidation of prochiral thioethers by racemic arylethyl hydroperoxides [62]. The latter reaction ends in (i )-sulfoxides, (S)-hydroperoxides and the corresponding (R)-alcohol, all In optically active forms. 

The activation of [bis(acyloxy)iodo]arenes with BF3 Et20 enables the conversion of protected glycals to frans-l,2-bis(acyloxy)glycosides (Scheme 17) [44]. In the presence of triflic acid, these compounds are excellent 2-acyloxygly-cosyl donors and can be utilized in situ with carbohydrate-based alcohols for the synthesis of disaccharides. 

Activation of resin-bound glycals by epoxidation followed by ring-opening or aminoglycosylation. 

Activation of 26 with AgBF, led to the intermediate 1,2-A-sulfonylaziridinc, which reacted with the tributyltin ether glycal 27 to afford the dimer 28. The second glycal was activated with dimethyldioxirane (DMDO) to supply the intermediate epoxide that was treated with ZnCl2 and allyl alcohol to afford compound 29. 

Efficient activation of the N-acetylated sialyl donor required l.Oequiv. of the Lewis acid under -78°C, giving the disaccharide 16 in 77% yield with excellent a selectivity (a/p=96/4, Table 8.2, entry 1). The conditions in entry 1 were reproducible under the microfluidic conditions (entry 2, 89% yield, a/p=94/6). Because the excess donor 15 inhibited the purification of sialoside 16 from the glycal by-product due to similar polarities on silica gel, the ratio between the donor and the acceptor... 

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