One pot/two donors/one diol give one differentiated trisaccharide: powerful evidence for reciprocal donor–acceptor selectivity (RDAS)

Fraser‐Reid, Bert; López, J. Cristóbal; Radhakrishnan, K. V.; Nandakumar, M. V.; Gómez, Ana M.; Uriel, Clara

doi:10.1039/b206598c

Cited by 36 publications

(21 citation statements)

References 7 publications

(6 reference statements)

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“…[42][43][44][45] Building on Paulsen notion that the reactivity of both reaction partners should be ''matched'' for an optimal glycosylation reaction, [46][47][48][49] Fraser-Reid coined the concept of reciprocal donor acceptor selectivity (RDAS), to account for these observations. [50][51][52][53] Although the concept still awaits a proper mechanistic explanation, the counter-intuitive outcome of several recent reactions have been related to this phenomenon. [54][55][56][57][58] To provide a satisfactory explanation for these observations, more insight is required into the intrinsic reactivity of (carbohydrate) acceptors and better (computational) methodology should be developed to assess the transition states of glycosylation reactions.…”

Section: Acceptormentioning

confidence: 99%

Acceptor reactivity in glycosylation reactions

et al. 2019

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Section: Acceptormentioning

confidence: 99%

Acceptor reactivity in glycosylation reactions

et al. 2019

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“…In that context, we decided to evaluate axial vs axial preference with the glycosylation of diol 88 [93]. [94]. Attempts to elicit equatorial vs equatorial selectivity were only partially successful (with vicinal diols) when an NPOE was used as glycosyl donor, whereas armed donors were less discriminating [93,95].…”

Section: Secondary Versus Secondary Hydroxyl Groups In Diolsmentioning

confidence: 99%

Armed–Disarmed Effects in Carbohydrate Chemistry: History, Synthetic and Mechanistic Studies

Fraser‐Reid¹,

López

2010

Reactivity Tuning in Oligosaccharide Assembly

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This chapter begins with an account of the serendipitous events that led to the development of n-pentenyl glycosides (NPGs) as glycosyl donors, followed by the chance events that laid the foundation for the armed-disarmed strategy for oligosaccharide assembly. A key mechanistic issue for this strategy was that, although both armed and disarmed entities could function independently as glycosyl donors, when one was forced to compete with the other for one equivalent of a halonium ion, the disarmed partner was found to function as a glycosyl acceptor. The phenomenon was undoubtedly based on reactivity, but further insight came unexpectedly. Curiosity prompted an examination of how ω-alkenyl glycosides, other than n-pentenyl, would behave. Upon treatment with wet N-bromosuccinimide, allyl, butenyl, and hexenyl glucosides gave bromohydrins, whereas the pentenyl analog underwent oxidative hydrolysis to a hemiacetal. Although the answer was definitive, an in depth comparison of n-pentenyl and n-hexenyl glucosides was carried out which provided evidence in support of the transfer of cyclic bromonium ion between alkenes in a steady-state phenomenon. It was found that for two ω-alkenyl glycosides having a relative reactivity ratio of only 2.6:1, nondegenerate bromonium transfer enabled the faster reacting entity to be converted completely to product, while the slower reacting counterpart was recovered completely. This nuance suggests that in the armed/disarmed coupling, such a nondegenerate steady-state transfer is ultimately responsible for determining how the reactants are relegated to donor or acceptor roles.Development of chemoselective armed/disarmed coupling led to another phase in the sequence of serendipities. During experiments to glycosylate an acceptor diol, it was found that armed and disarmed donor's glycosylated different hydroxyl groups. This observation caused us to embark on studies of regioselective glycosylation. One of these studies showed that it is possible to activate selectively n-pentenyl orthoesters (NPOEs) over other n-pentenyl donors, and that this chemoselective process enables regioselective glycosylation. As a result, reaction partners can be so tuned that glycosylation of an acceptor with nine free hydroxyl groups by an n-pentenyl orthoester donor carrying two free hydroxyl groups is able to furnish a single product in 42% yield. Experiments such as the latter suggest that the donor favors a particular hydroxyl group, and/or that a particular hydroxyl favors the donor. Either option implies that the principle of reciprocal donor acceptor selectivity (RDAS) is in operation.Such examples of regioselective glycosylation provide an alternative to the traditional practice of multiple protection/deprotection events to ensure that the only free hydroxyl group among glycosyl partners is the one to be presented to the donor. By avoiding such protection/deprotections, there can be substantial savings of time and material - as well as nervous anxiety.

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“…14 With a number of different concepts for the one-pot synthesis, we chose the one-pot/one-addition method wherein all of the building blocks are present from the beginning. Invented by Kahne, 15 and further explored by Fraser-Reid 16 and Bols, 7 a this approach requires fine tuning of the reactivity to differentiate all of the reaction components. The general idea underpinning this approach is that the more reactive donor will react with the more reactive acceptor (hydroxyl).…”

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confidence: 99%

Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot

et al. 2017

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A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.

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One pot/two donors/one diol give one differentiated trisaccharide: powerful evidence for reciprocal donor–acceptor selectivity (RDAS)

Abstract: Three component, one-pot reactions involving equimolar amounts of the acceptor diol and both armed and disarmed donors presented simultaneously, produce a single double-differential glycosidation product; this phenomenon provides evidence for Reciprocal Donor Acceptor Selectivity (RDAS).

Cited by 36 publications

References 7 publications

Acceptor reactivity in glycosylation reactions

Acceptor reactivity in glycosylation reactions

Armed–Disarmed Effects in Carbohydrate Chemistry: History, Synthetic and Mechanistic Studies

Conformationally superarmed S-ethyl glycosyl donors as effective building blocks for chemoselective oligosaccharide synthesis in one pot

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