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

Abstract

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 timeeffective approach and an applicable and convenient analytical method for determining the absolute configuration of one secondary alcohol in natural products.

Suppression of 6-Hydroxydopamine-Induced Oxidative Stress by Hyperoside Via Activation of Nrf2/HO-1 Signaling in Dopaminergic Neurons

“…The isolated compounds were identified as (7 S ,8 R )-1′,4-dihydroxy-3,3′,5′-trimethoxy-7′,8′,9′-trinor-8,4′-oxyneoligna-7,9-diol ( 1 ) [32], 4,4′-((1 R ,2 R )-3-hydroxy-1-methoxypropane-1,2-diyl)-bis-2-methoxyphenol ( 2 ) [33], 1- O -β- d -(6′′- O -galloyl)-glucopyranoside ( 3 ) [34], naringenin-4′- O -β- d -glucopyranoside ( 4 ) [35], hyperoside ( 5 ) [36], quercetin 3-β- d -xylopyranoside ( 6 ) [37], avicularin ( 7 ) [38], guaijaverin ( 8 ) [39], 6,8-dihydroxy-7-methoxy-2 H -1-benzopyran-2-one ( 9 ) [40], 6-hydroxy-7-methoxy-2 H -1-benzopyran-2-one ( 10 ) [41], ( E )-ferulic acid ( 11 ) [42], 4-hydroxy-benzeneethanol ( 12 ) [43], 2-hydroxy-4-methoxyphenol ( 13 ) [44], 4-hydroxy-benzoic acid ( 14 ) [45] and syringic acid ( 15 ) [46] by comparing their NMR spectroscopic and physical data with those reported in the literature, and by measuring their specific rotations as well as via LC/MS analysis.…”

Simultaneous separation and detection chiral fenobucarb enantiomers using UPLC–MS/MS

“…The stereostructure of fenobucarb contains a chiral center, which leads to a pair of enantiomers. Optical isomers exhibit similar chemical and physical properties, while their bioactivity, toxicity, absorption, transformation and degradation behaviors are generally enantioselective [8][9][10][11]. A research shows that another carbamate chiral pesticide isoprocarb have enantioselective behavior that the more efficient S-isoprocarb degraded faster than that of R-isoprocarb in the cucumber, tomato, cabbage and soil.…”

Bioactive compounds from the seeds of Amomum tsaoko Crevost et Lemaire, a Chinese spice as inhibitors of sphingosine kinases, SPHK1/2

“…6). 32 We further referred to properties of chemical substances with similar chemical equivalence as compound 5. The values of specic rotation were compared, [a] 25 D +17.9 for compound 5 and [a] 25 D +13 for methyl-(10R)hydroxyhexadeca-(7Z,11E,13Z)-trienoate, 33 and conrmed compound 5 as (11R)-hydroxyhexadeca-(2E,7Z,9E)-trienoic acid.…”

“…CEA reaction. Parallel reactions for the CEA reaction were performed as reported by Lee et al, 32 using S-and R-HBTM. Compound 5 (0.2 mg, 0.75 mmol) was transferred to two transparent, capped 5 mL vials at room temperature, and DMF (90 mL) was added as the organic solvent for the CEA reaction.…”