Synthesis of C‐2‐ and C‐3‐Sulfonatomethyl O‐ and S‐Glycosides by Horner–Wadsworth–Emmons Olefination

Abstract

The applicability of the Horner–Wadsworth–Emmons olefination to the introduction of the sulfonatomethyl moiety at the 2‐ and 3‐positions of orthogonally protected O‐ and S‐glycosides has been studied. The conformational preferences and relative energies of the exo‐ and endocyclic alkenesulfonic acids obtained were analysed by high‐temperature molecular dynamics and DFT calculations. Thioglycosides bearing a sulfonatomethyl moiety at the secondary position have been prepared for the first time. Finally, the attempted synthesis of 2‐sulfonatomethyl glucoside by nucleophilic substitution reaction is also described.

Testing the Simplified Molecular Dynamics Approach to Improve the Reproduction of ECD Spectra and Monitor Aggregation

“…The SHAKE algorithm [ 61 ] was used to keep the bond lengths of hydrogen atoms rigid allowing a time step of 2 fs to be used. The MD simulations were carried out using AMBER simulation engine version 12 [ 14 , 62 ] using an NVT ensemble at 300 K. First, a minimization was performed for 10,000 steps starting with the steepest descent algorithm, which is switched to the conjugate gradient algorithm after 100 steps. After minimization a constant pressure MD was carried out for 0.4 ns with isotropic position coupling using a Berendsen barostat to equilibrate the system, during which the density stabilized, and the temperature settled at 300 K. Then, the pressure regulation was switched off and a classical constant total energy MD producing microcanonical NVE ensemble was carried out for 4 ns or 100 ns.…”

“…According to the generally applied protocol for the computation of ECD or other chiroptical data of small- or medium-molecular-weight derivatives, an initial conformational search is performed at a low level (usually molecular mechanics (MM) level implemented in different programs, e.g., Macromodel [ 8 ], Conflex [ 9 ] or Spartan [ 10 ]) as the first step to generate conformers systematically or by a specific algorithm [ 9 , 11 , 12 ]. Molecular dynamics (MD) offers an alternative way to generate the conformers at normal [ 13 ] or elevated temperature [ 14 ], which is however less utilized in chiroptical methods [ 13 , 15 , 16 ].…”

“…The accustomed utilization of MD conformers is similar to the ones obtained by the classical conformational search. They are optimized at a low (usually MM) level and then re-optimized at an advanced DFT level after clustering [ 13 , 14 , 15 , 33 , 35 ]. In order to address intermolecular interactions, which is not feasible with the classical ECD calculation approach, molecular complexes are sometimes extracted from the dynamics or generated manually [ 16 , 36 , 37 , 38 ].…”

A Modular Synthetic Approach to Isosteric Sulfonic Acid Analogues of the Anticoagulant Pentasaccharide Idraparinux

“…With the aim of developing a novel class of heparinoid anticoagulants, our group has started a programme to study whether the sulfate ester groups of the active pentasaccharide can be exchanged with sulfonic acid moieties without detriment to the antithrombin-binding ability [10,11,12,13,14,15,16,17,18,19]. Two pentasaccharide sulfonic acids ( 4 and 5 ) and the reference compound idraparinux 3 have been prepared until now.…”