J. Cristóbal López

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

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 donors 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.

n-Pentenyl esters facilitate an oxidative alternative to the Ferrier rearrangement. An expeditious route to sucrose

Ferrier-type reactions can now be carried out under non-acidic conditions by treating 3-n-pentenoyl glycals with iodonium dicollidinium perchlorate whereupon the terminal double bond is chemoselectively activated to furnish an allylic oxo-carbenium ion which reacts at the anomeric position with monosaccharide alcohols to afford 2,3-unsaturated disaccharides in fairly good yields.

Stereoselective synthesis of substituted exo-glycals from 1-exo-methylene pyranoses

Halo-exo-glycals of the gluco-, manno- and galacto- series, readily prepared by reaction of 1-exo-methylene pyranoses with iodonium dicollidinium triflate (IDCT), undergo Suzuki or B-alkyl Suzuki cross-coupling reactions with boronic acids or alkyl boranes to yield, in a stereoselective manner, functionalized exo-glycals.

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

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).

Thioglycoside and trichloroacetimidate donors in regioselective glycosidations. Comparison with n-pentenyl glycosides

Thioglycoside and trichloacetimidate donors show the same regiopreferences as NPG analogs for selective glycosidation of an altroside diol, indicating that the selectivity may be general for donors. They also undergo one-pot, double-differential-glycosidations to give a single trisaccharide out of four possibilities.

Six- versus five-membered ring formation in radical cyclization of 1-vinyl-5-methyl-5-hexenyl radicals

Abstract Radical cyclization of 1-vinyl-5-methyl-5-hexenyl radicals (radical numbering) affords six-membered ring products prevailing over the isomeric five-membered ring compounds; the former are generated through two reaction pathways: 6- endo – trig ring closure and rearrangement of intermediate methylenecyclopentyl radicals obtained by 5- exo – trig cyclization.

A general stereodivergent strategy for the preparation of carbasugars. Syntheses of 5a-carba-α-d-glucose, α-d-galactose, and β-l-gulose pentaacetates from d-mannose

A stereodivergent approach to 5a-carba-d- and l-pyranoses has been applied to the preparation of 5a-carba-α-d-gluco-, 5a-carba-α-d-galacto-, and 5a-carba-β-l-gulopyranose pentaacetates. The strategy, by which a single precursor can be transformed into three different carbasugars, features a stereoselective reduction followed by deoxygenation of a key polyoxygenated methylcyclohexanone intermediate. The latter is readily available by 6-exo-dig radical cyclization of a d-mannose derivative.

One-pot synthesis of 1-exo-alkylidene-2,3-anhydro furanoses: convenient precursors for exo-glycals and functionalized C-glycals

1-exo-Methylene-2,3-anhydro furanoses, obtained from C-glycals in a one-pot, three step operation can be readily transformed into functionalized C-glycals by palladium-catalyzed nucleophilic addition.

Two terpenoids from salvia bicolor

Abstract Two new terpenoids, 20( S ),24( R )-epoxy-dammar-12,25-diol-3-one and 12-methoxy-11,7-dihydroxydehydroabietane, were isolated from the roots of Salvia bicolor .

Stereoselective synthesis of C-ketosides by Lewis acid-catalyzed C-glycosylation of alkynyl-ketoses

C-Ketosides are conveniently prepared in a stereoselective manner from alkynyl-ketoses by reaction with carbon nucleophiles in the presence of a Lewis acid.