Synthesis and Quantitative Analysis of Diastereomeric Linked Ester Conjugates With Remote Stereocenters Using High-Field NMR and Chiral HPLC

Autor: Tõnis Pehk, Ly Villo, Omar Parve, Lauri Vares, Eva Doyle, Aleksander-Mati Müürisepp, Jaan Parve, Sven Tamp, Marina Kudryashova
Rok vydání: 2013
Předmět:
Zdroj: Chirality. 25:793-798
ISSN: 0899-0042
DOI: 10.1002/chir.22217
Popis: A stereochemically safe high-yielding procedure for linking unprotected as well as protected hydroxycarboxylic acids to chiral secondary alcohols via glycolic acid linker is proposed. L-menthol has been linked with both enantiomers of mandelic, malic, and methoxyphenylacetic acid using bromo- or iodoacetyl group as a precursor of the glycolic acid linker. High-field nuclear magnetic resonance (NMR) and chiral high-performance liquid chromatography (HPLC) determination of high diastereomeric ratio (dr) (>99%) of the products bearing remote stereocenters was explored. Chiral HPLC allowed quantitation of the diastereomers up to dr 99.9/0.1. High-field NMR quantitation of the diastereomeric and parent alcoholic impurities in esters was demonstrated at the molar 0.3% and 0.03% levels, respectively. These analyses were done via comparison of integral intensities from major component 13C satellites in 1H or even in 13C spectra to the 1H or 13C signals of impurities. Despite lower sensitivity, the last option generally has much better selectivity. In this way the dynamic resolution is brought down by two orders. Chirality 25:793–798, 2013. © 2013 Wiley Periodicals, Inc.
Databáze: OpenAIRE
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