Dutch Resolution: Separationof Enantiomers with Families of Resolving Agents. A Status Report

Abstract

Dutch Resolution is the term given to the use of mixtures (families) of resolving agents in classical resolutions. In this status report an overview is given of the latest results and new (possible) families of resolving agents are introduced. The concept of families is discussed as well as the factors that come into play on use of families. Practical aspects of Dutch Resolution in particular and resolutions in general are discussed.

Development of a Mild Procedure for the Addition of Bisulfite to Electrophilic Olefins

“…[1] For this reason, they have been often used as resolving agents for chiral racemic amines, [2] and families of sulfonic acids were prepared and used in "Dutch resolution" experiments. [3,4] Sulfonic acids and sulfonamides are isosteric with carboxylates which justifies their popularity in medicinal chemistry. [5] Taurine and some of its derivatives (e.g., homotaurine, guanidotaurine) have repeatedly being found to have activity on the central nervous system (CNS).…”

“…The harsh conditions effectively limited the synthetic utility of this reaction with the reports of Kellogg [4] and Crowley [14] being the only variant described recently. Kellogg reported the addition of solid sodium bisulfite to chalcones in ethanol at reflux; [4] Crawley and co-workers have successfully optimized a microwave-assisted sulfonylation of cinnamic acid ester derivatives using aqueous sodium bisulfite. [14] Both these procedures required the use of high temperature and a large excess of bisulfite reactant.…”

Chiral discrimination in the solid state by using the Dutch resolution method

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TPB (1,1,4,4-tetraphenyl-1 ,3-butadiene) is a luminescent molecule that displays luminescence also in the crystalline state, if favorably packed by aligning the transition dipoles in the correct orientation.TPB is currently known in three polymorphs a, b, g, [1], and TPB molecular structure approximately displays C 2 point symmetry in the a form, and C i point symmetry in b and g. Among these the b form has proved to be best suited to photoluminescence; unfortunately its crystallization is not reproducible. The g form, structurally very similar to the b polymorph, is also rarely obtained.

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“…Unexpected behaviour of seeding experiments on the melt will be also discussed and rationalized by means of structural analysis and of PXRD, DSC, Raman, SS-NMR experiments. [1] Girlando, A., Iannelli, S., Bilotti, I., Brillante , A., Della Valle, R,G., Venuti, E.,Campione , M., Mora, S., Silvestri, L., Spearman, P., Silvia , T . The worldwide sales of the single enantiomer drug market was about $300 billion in 2010.…”

“…An estimated 30-50% of these drugs have been obtained by classical resolution methods. [1] The main reason why chiral discrimination is one of the hot topics of chemistry is that after years of extensive research we still do not fully understand the mechanism of chiral discrimination and cannot design the 'perfect' resolving agent.…”