Stereospecific Ester Activation in Nitrite-Mediated Carbohydrate Epimerization

Abstract

[reaction: see text] The Lattrell-Dax method of nitrite-mediated substitution of carbohydrate triflates is an efficient method to generate structures of inverse configuration. In the present study, epimerization of gluco- and galactopyranoside derivatives to the corresponding allo- and gulopyranoside structures by triflation/nitrite treatment has been investigated. It was found that a neighboring ester group was essential for the reactivity of the nitrite-mediated triflate inversion. Furthermore, a good inversion yield also depended on the relative configuration of the neighboring ester group to the triflate. Only with the ester group in the equatorial position, whatever the configuration of the triflate, did the reaction proceed smoothly, whereas a neighboring axial ester group proved largely inefficient. The results were subsequently used to predict the inversion of glucopyranoside derivatives to the mannopyranoside epimers.

Synthesis of the C-glycoside of α-d-mannose-(1 → 6)-d-myo-inositol

“…The crude product was treated with potassium nitrite in DMF at 50 °C to give the desired alcohol 25 in 80% yield over two steps. 32 The manno configuration and the 3′ C 6′ conformation of 25 was supported by J values ( J 2′,3′ = J 3′,4′ = 9.6 Hz; J 4′,5′ = J 5′,6′ = 0 Hz) and H-2′/H-4′ and H-4′/H-7′ nOe’s. Straightforward removal of alcohol protecting groups in 25 provided the target α- C-manno -pyranosyl- myo -inositol 4 .…”

Synthesis of 4” manipulated Lewis X trisaccharide analogues

“…A Lattrell-Dax nitrite mediated inversion [58–60] of the 4-OH in galactoside 15 provided the glucoside 17 , which was used as the common precursor to analogues 18 and 19 . Treatment with sulfuryl chloride [61] gave the 4-chloro galactoside 18 in good yield, whereas triflation at O-4 followed by S N 2 displacement of the triflate by using tetrabutylammonium fluoride [62–63] gave the 4-fluoro galactoside analogue 19 in excellent yields.…”

Synthesis and evaluation of galacto-noeurostegine and its 2-deoxy analogue as glycosidase inhibitors

“…To eventually reach the galacto-configuration, an early epimerisation at the 3-position was envisaged. This lack of reactivity can be explained by the absence of a neighbouring ester group in an equatorial position, as described by Ramström et al 19 Furthermore, it was hypothesised that the steric hindrance of the bottom face resulted in a nitrite ion attack on the sulfur atom of the triflate rather than on C-3, giving rise to the initial alcohol with liberation of nitrosyl triflate. Triflation of alcohol 7 followed by nitritemediated substitution according to the Lattrell-Dax method was attempted, 18 unfortunately leading to full recovery of the starting material.…”

“…Similarly, the anomeric mixture was used in the following zinc-mediated fragmentation, under sonication, 22 to give a unique hexenal 16 which was subsequently allylated in a Barbier-type reaction, affording a separable 3 : 2 diastereoisomeric mixture of homoallylic alcohols 17R/17S. The undesired diastereomer (18R) was then efficiently converted to its epimer (18S) after PCC oxidation (19) and lithium tri-tert-butoxyaluminium hydride reduction (82% over two steps). Gratifyingly, unlike their gluco counterparts, 6 the ring closing metathesis could be performed without the need for protection of the homoallylic alcohol moieties and each diastereomer gave its corresponding cycloheptene in 78% yield.…”

“…(5R,6S,7R)-5,6-Di-O-benzyl-7-C-benzyloxymethyl-cyclohept-3en-1-one (19). To a solution of alcohol 18R (2.92 g, 6.57 mmol) in dry DCM (25 mL) and under an argon atmosphere, was added silica gel (63-200 µm, 4 g) then PCC (22.42 g, 104 mmol, 2.5 eq.)…”