Anomeric selectivity

The results obtained by using this reagent system are comparable to those achieved using such alternative catalysts as Sc(OTf)3, Yb(OTf)3, CAN, and BF3 Et20, and even better in some cases, in terms of yield, reaction time, and anomeric selectivity. 

This method has been used only a few times, despite the high yields reported. In the procedure, the hemiacetal was activated with tributylphosphine oxide (4.5 equiv) and triflic anhydride (2.1 equiv) for 2 h at 0 °C, followed by an addition of the giycosyi acceptor. As a result, the isopropyl riboside 46 was prepared in 93% and the cho-lestanyl riboside 47 was prepared in 75%, both with a-anomeric selectivity. 

This procedure has been demonstrated to provide moderate yields and anomeric selectivity in oligosaccharide synthesis. For instance, the disaccharide 110 was obtained in 50% yield as a 1 2 a p ratio. The reaction side products were mainly the self-condensed donor (10-25%) and unreacted hemiacetal (5-10% or higher). Alternatively, the a-linked glycosides were favored with diethyl ether solvent. In this way, trisaccharide 111 was prepared from the disaccharide hemiacetal donor in 49% yield, favoring the a-anomer by 4 1. 

Ziegler and coworkers prearranged a glycoside by employing a succinyl tether between C-6 of a mannosyl donor and C-3 of glucosyl acceptor [151,152]. They found that the nature of the glycosyl acceptor and the length of the tether affected the anomeric selectivity of the intramolecular mannosylation (Scheme 4.4d) [153]. 

Yet another approach uses peptides as tethers for intramolecular glycosylations via prearranged glycosides (Scheme 5.113) [326,327]. The regio- and anomeric selectivity of the intramolecular glycosylation depends on the amino acid sequence of the peptide, which links glycosyl donor and acceptor. 

Thus, the latter approach was clearly preferable and several NPG donors were coupled to 41 under these conditions in order to investigate trends in anomeric selectivity, as monitored by gel-phase 13C NMR spectroscopy (Table 5.1).66 As expected, neighboring-group active donors 44 and 45 produced solely the... 

Anomeric selectivity is diminished in the case of 0,/V-acetals. This means that the starting hemiacetal may give a mixture of a- or /J-anomers with amines. Therefore, a measurement of diastereomeric ratios is less useful than in the case of pure 0,0-acetals. Secondary amino compounds may react cleanly with the e.w-MBF-OH, whereas primary amines give, with both starting materials, mixtures of a- and /J-anomers. 

Our first disconnection revealed glycosyl monophosphate 7 and undecaprenyl monophosphate 8.11 This disconnection was chosen because previous work, directed toward the synthesis of the Park Nucleotide 3, had shown it possible to introduce an anomeric phosphate with anomeric selectivity in favor of the desired a-anomer. A second reason for choosing this disconnection was that undecaprenyl monophosphate was available for purchase from a commercial source. Thus, if we could identify a mild method for joining these two fragments, only a global deprotection step would be required to arrive at lipid I. 

The initial target for our chemical synthesis of lipid I was phosphomuramyl pentapeptide 9. At the outset, we were confident in our ability to prepare the monosaccharyl pentapeptide core structure, but were unsure of our ability to install the anomeric phosphate with the desired a-stereochemistry. We were also concerned about the timing for introduction of the anomeric phosphate since solubility and anomeric selectivity could be strongly influenced by the presence or absence of the peptapeptide side chain. In addition, we had not settled on a method for... 

New strategies for preparing either 1,2-cis- or 1,2-trans-glycosides stereoselectively have been reported.61 A chiral auxiliary containing a nucleophile is used to control the anomeric selectivity of the glycosylation. A sample reaction is shown in Scheme 8. 

Another popular promoter for glycosylation with thioglycosides is the reagent dimethyl(methylthio)sulfonium triflate (DMTST).60 A comparison between DMTST and NIS/TfOH for the formation of sialoglycoconjugates demonstrated that the iodine system provided superior yields and anomeric selectivity in nearly all cases.61 The yields and stereoselectivity also increased with an increase in solvent polarity, suggesting that enhanced stabilization of the oxacarbenium intermediate, the rate-limiting step in glycosylation, was responsible for the increased... 

The use of the hypervalent iodine reagent [bis(trifluoroacetoxy)iodo]benzene has been reported to be effective in the synthesis of C-nucleoside-like compounds. Radical decarboxylation of a suitably protected uronic acid, initiated photochem-ically, followed by addition of a heterocyclic base provided the C-nucleoside in high yield.154 The mode of action involves initial radical formation of 122 (Scheme 33), followed by introduction of the base and radical coupling.155 The anomeric selectivity was high in some examples, and low in others—lepidine gave the highest proportion of the ( anomer. Isolated yields were poor to moderate. 

Additional problems of anomeric phosphorylation are the control of anomeric selectivity and the increased lability of the products. The preparation of anomeric sugar phosphates can be accomplished via two distinct methods. The first commences with a free anomeric hydroxyl and can be considered as a standard phosphorylation. The second approach... 

It is essential that the in situ anomerisation is performed in a solvent of low polarity. In polar solvents, the reaction proceeds via an oxocarbenium ion and the anomeric selectivity is reduced. 

Some solvents may form complexes with the oxocarbenium ion intermediates, thereby affecting the anomeric outcome of a glycosylation. For example, diethyl ether is known to increase the a anomeric selectivity. Probably, diethyl ether participates by the formation of diethyl oxonium ion (Scheme 4.9a). The (3 configuration of this intermediate is favoured because of the operation of the reverse anomeric effect (see Chapter 1). Nucleophilic displacement with inversion of configuration will give an a glycoside. Recently, it was shown that a mixture of toluene and dioxane provides a more efficient participating solvent mixture. 

Thus, it appears that a rigid five-membered ring transition state is important for high anomeric selectivities. 

---