Hydrogen‐Bonding Cooperativity: Using an Intramolecular Hydrogen Bond To Design a Carbohydrate Derivative with a Cooperative Hydrogen‐Bond Donor Centre

Abstract

Neighbouring groups can be strategically located to polarise HO.OH intramolecular hydrogen bonds in an intended direction. A group with a unique hydrogen-bond donor or acceptor character, located at hydrogen-bonding distance to a particular OH group, has been used to initiate the hydrogen-bond network and to polarise a HO.OH hydrogen bond in a predicted direction. This enhanced the donor character of a particular OH group and made it a cooperative hydrogen-bond centre. We have proved that a five-membered-ring intramolecular hydrogen bond established between an amide NH group and a hydroxy group (1,2-e,a), which is additionally located in a 1,3-cis-diaxial relationship to a second hydroxy group, can be used to select a unique direction on the six-membered-ring intramolecular hydrogen bond between the two axial OH groups, so that one of them behaves as an efficient cooperative donor. Talose derivative 3 was designed and synthesised to prove this hydrogen-bonding network by NMR spectroscopy, and the mannopyranoside derivatives 1 and 2 were used as models to demonstrate the presence in solution of the 1,2-(e,a)/five-membered-ring intramolecular hydrogen bond. Once a well-defined hydrogen-bond is formed between the OH and the amido groups of a pyranose ring, these hydrogen-bonding groups no longer act as independent hydrogen-bonding centres, but as hydrogen-bonding arrays. This introduces a new perspective on the properties of carbohydrate OH groups and it is important for the de novo design of molecular recognition processes, at least in nonpolar media. Carbohydrates 1-3 have shown to be efficient phosphate binders in nonpolar solvents owing to the presence of cooperative hydroxy centres in the molecule.

Synthesis of modified D-mannose core derivatives and their impact on GH38 α-mannosidases

“…The residue was purified by column chromatography (hexane:EtOAc 4:1→2:1) providing 9 (0.20 g, 93%) as a colourless oil. 1 (10) 22 .…”

“…Other target derivatives, phenyl and benzyltriazolyl rhamnosides 14 and 15, were synthesised by Cu(I) catalysed azide-alkyne cycloaddition (CuAAC) reaction of azide 10 22 with the corresponding alkynes. Synthesis of 10 was accomplished from methyl α-Dmannopyranoside 6 by the same sequence as reported for 3 (tosylation, benzoylation, reduction), followed by debenzoylation and acetylation of secondary hydroxyls leading to peracetylated methyl α-D-rhamnoside 8.…”

“…Found: 523.1257.4.2.1.22. (6S) Benzyl 6-C-methyl-α-D-mannopyranosyl sulfone(22).Deprotection of compound 21 (30 mg, 0.06 mmol) according to general procedure (Method D) and purification by column chromatography (CH3CN:MeOH 9:1) afforded 22 (17 mg, 85%) as a white foam. [α]D + 98 (c 0.4, MeOH); 1 H NMR (400 MHz, CD3OD): δ 7.51-7.40 (m, 5H, Ar), 4.84 (d, 1H, J1,2 1.6 Hz, H-1), 4.60 (d, 1H, J 14.0 Hz, CH2Ph), 4.41 (dd, 1H, J2,3 3.1 Hz, H-2), 4.36 (d, 1H, J 14.0 Hz, CH2Ph), 4.17 (dq, 1H, Jd 1.8 Hz, Jq 6.6 Hz, H-6), 4.05-3.96 (m, 3H, H-3, H-4, H-5), 1.43 (d, 3H, J 6.7 Hz, C-7(CH3)); 13 C NMR (100 Mz, CD3OD)…”

A Neutral DNA Sequence‐Selective Vector for Interaction Studies: Fluorescence Binding Experiments Directed Towards a Carbohydrate‐DNA Carrier

“…Initially we explored the use of carbohydrate hydrogen bonding cooperativity [42][43][44][45] to favour DNA binding and we characterised sugar H-bonding patterns that efficiently bind CG [46] and phosphate [47,48] in apolar solvents. In order to establish the efficiency of these binding elements to the biological target and under physiological conditions we first need to design a vector molecule: a compound that will bring our new designed binding motives to the minor groove of DNA without complete loss of interaction and binding sequence selectivity, hopefully to fix the carbohydrate to a unique binding site of a designed oligonucleotide.…”

Multivalent Presentation of Mannose on Hyperbranched Polyglycerol and their Interaction with Concanavalin A Lectin

“…[29] In the case of azido-Man, the azido functionality at the anomeric position was introduced via the corresponding peracetylated a,b-d-mannopyranose by reacting with trimethylsilylazide (TMSN 3 ) catalyzed by SnCl 4 . [30] Subsequently, the Man residues were clicked onto the prefunctionalized surface of hPG via triazole linkage by standard Sharpless/ Huisgen click chemistry [31] in an overall highly efficient process. The versatile nature of this reaction has led to a tremendous application in polymer chemistry, mainly due to the quantitative yields and the possibility of carrying out the synthesis in either organic solvents or water.…”