High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening

Elena G. Shcherbakova, Valentina Brega, Vincent M. Lynch, Tony D. James, Pavel Anzenbacher

Research output: Contribution to journalArticle

8 Citations (Scopus)
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Abstract

A simple and efficient method for determination of the yield, enantiomeric/diasteriomeric excess (ee/de), and absolute configuration of crude chiral diols without the need of work-up and product isolation in a high throughput setting is described. This approach utilizes a self-assembled iminoboronate ester formed as a product by dynamic covalent self-assembly of a chiral diol with an enantiopure fluorescent amine such as tryptophan methyl ester or tryptophanol and 2-formylphenylboronic acid. The resulting diastereomeric boronates display different photophysical properties and allow for fluorescence-based ee determination of molecules containing a 1,2- or 1,3-diol moiety. This method has been utilized for the screening of ee in a number of chiral diols including atorvastatin, a statin used for the treatment of hypercholesterolemia. Noyori asymmetric hydrogenation of benzil was performed in a highly parallel fashion with errors <1 % ee confirming the feasibility of the systematic examination of crude products from the parallel asymmetric synthesis in real time and in a high-throughput screening (HTS) fashion.

Original languageEnglish
Pages (from-to)10222-10229
Number of pages8
JournalChemistry - A European Journal
Volume23
Issue number42
Early online date6 Jul 2017
DOIs
Publication statusPublished - 26 Jul 2017

Fingerprint

Assays
Screening
Throughput
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Self assembly
Hydrogenation
Amines
Esters
Fluorescence
Molecules
tryptophanol
benzil
Atorvastatin Calcium
2-formylphenylboronic acid
tryptophan methyl ester

Keywords

  • asymmetric catalysis
  • diols
  • enantiomeric excess
  • fluorescence
  • self-assembly

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening. / Shcherbakova, Elena G.; Brega, Valentina; Lynch, Vincent M.; James, Tony D.; Anzenbacher, Pavel.

In: Chemistry - A European Journal, Vol. 23, No. 42, 26.07.2017, p. 10222-10229.

Research output: Contribution to journalArticle

Shcherbakova, Elena G. ; Brega, Valentina ; Lynch, Vincent M. ; James, Tony D. ; Anzenbacher, Pavel. / High-Throughput Assay for Enantiomeric Excess Determination in 1,2- and 1,3-Diols and Direct Asymmetric Reaction Screening. In: Chemistry - A European Journal. 2017 ; Vol. 23, No. 42. pp. 10222-10229.
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