Highly Sensitive, Simple, and Cost- and Time-Effective Method to Determine the Absolute Configuration of a Secondary Alcohol Using Competing Enantioselective Acylation Coupled with LC/MS

• Published in: Analytical chemistry (Washington) 2018-11, Vol.90 (22), p.13212-13216
• Main Authors: Lee, Seoung Rak, Park, Hyun Bong, Kim, Ki Hyun
• Format: Article
• Language: English
• Subjects: Absolute configuration; Aceraceae - chemistry; Acylation; Alcohol; Alcohols; Alcohols - chemistry; Alcohols - isolation & purification; Biological Products - chemistry; Catalysis; Catalysts; Catechin - chemistry; Chemistry; Chromatography; Chromatography, Liquid - methods; Computer applications; Configurations; Cost analysis; Dichroism; Enantiomers; Functional groups; Hydroxyl groups; Identification methods; Kinetics; Laurates - chemistry; Mass spectrometry; Mass Spectrometry - methods; Mathematical analysis; Molecular Structure; Monoglycerides - chemistry; Natural products; NMR; Nuclear magnetic resonance; Organic chemistry; Quantum chemistry; Stereoisomerism; Stereoisomers; Synthetic biology; Trichothecenes - chemistry
• ISSN: 0003-2700; 1520-6882
• DOI: 10.1021/acs.analchem.8b03385

The absolute-configuration determination of natural products and synthetic compounds with stereogenic centers is very important because stereoisomers dramatically and differentially affect many crucial properties, such as physical behaviors and biological functions. Despite several established methods for determining the absolute configuration, significant unmet needs for new methods still exist owing to the specific limitations of established methodologies. Here, we present a simple, optimized, new chemical-derivative method that utilizes competing enantioselective acylation followed by LC/MS analysis, and we demonstrate its successful application in determining the absolute configuration of a secondary alcohol in natural products with multiple reactive functional groups. This new development relies on the enantiomeric pair of homobenzotetramisole (HBTM) catalysts exhibiting adequate kinetic resolution for acylation of the secondary alcohol, and then the fast reaction was quantitatively confirmed via LC/MS as the characterization technique for the enantioselective transformations. Our new approach was successfully applied to determine the absolute configuration of one secondary alcohol in compound 1, which has other hydroxyl groups to be reacted. The identified stereocenter of 1 was verified by previously established methods including quantum chemical electronic-circular-dichroism (ECD) calculations, computational NMR-chemical-shift calculations followed by DP4+ calculations, and modified Mosher’s method. In addition, our method was applied to five known naturally occurring compounds, which led to the successful verification of their absolute configurations. Our newly developed method using the HBTM catalyst provides a highly sensitive, simple, and cost- and time-effective approach and an applicable and convenient analytical method for determining the absolute configuration of one secondary alcohol in natural products.