Enantiomeric high-performance liquid chromatography resolution and absolute configuration of 6β-benzoyloxy-3α-tropanol

Abstract

The absolute configuration of the naturally occurring isomers of 6β-benzoyloxy-3α-tropanol (1) has been established by the combined use of chiral high-performance liquid chromatography with electronic circular dichroism detection and optical rotation detection. For this purpose (±)-1, prepared in two steps from racemic 6-hydroxytropinone (4), was subjected to chiral high-performance liquid chromatography with electronic circular dichroism and optical rotation detection allowing the online measurement of both chiroptical properties for each enantiomer, which in turn were compared with the corresponding values obtained from density functional theory calculations. In an independent approach, preparative high-performance liquid chromatography separation using an automatic fraction collector, yielded an enantiopure sample of OR (+)-1 whose vibrational circular dichroism spectrum allowed its absolute configuration assignment when the bands in the 1100-950 cm(-1) region were compared with those of the enantiomers of esters derived from 3α,6β-tropanediol. In addition, an enantiomerically enriched sample of 4, instead of OR (±)-4, was used for the same transformation sequence, whose high-performance liquid chromatography follow-up allowed their spectroscopic correlation. All evidences lead to the OR (+)-(1S,3R,5S,6R) and OR (-)-(1R,3S,5R,6S) absolute configurations, from where it follows that samples of 1 isolated from Knightia strobilina and Erythroxylum zambesiacum have the OR (+)-(1S,3R,5S,6R) absolute configuration, while the sample obtained from E. rotundifolium has the OR (-)-(1R,3S,5R,6S) absolute configuration.

Chiral Chromatographic Analysis and Absolute Stereochemistry of Racemic Chlorpheneramine Using Chiral HPLC-Cd-or and Td-DFT Calculations

“…We recently reported the use of this approach in the study of the chiroptical properties of racemic trans-stilbene oxide 7 and the absolute configuration assignment of the tropane alkaloid 6-benzoyl-3-tropanol, 8 both in agreement with literature data and VCD observations, respectively.…”

Vibrational Circular Dichroism Absolute Configuration of Natural Products From 2015 to 2019

“…Preparation of (±)− 262 and chiral resolution allowed determining the AC of the natural occurring isomer as (+)-(1 S ,3 R ,5 S ,6 R )−6 β -benzoyloxy-3 α -tropanol ( 262 ) (Figure 75), present in Knightia strobilina and Erythroxylum zambesiacum , by a combined use of chiral HPLC with ECD, OR, and VCD. 125…”

“…The AC of both compounds was ascertained by VCD spectroscopy. 69 ECD, Raman optical activity, and VCD methodologies were used to characterize (3R,3'R)-astaxanthin (125) and (3S,3′S)astaxanthin (126) ( Figure 33). Commercially available racemic astaxanthin was separated into the enantiomers by column chromatography after bis-[(−)camphanic] ester derivatization.…”

“…124 Preparation of (±)−262 and chiral resolution allowed determining the AC of the natural occurring isomer as (+)-(1S,3R,5S,6R)−6β-benzoyloxy-3α-tropanol (262) (Figure 75), present in Knightia strobilina and Erythroxylum zambesiacum, by a combined use of chiral HPLC with ECD, OR, and VCD. 125 A commercial sample of tropane (−)-(1R,2R,3S,5S)-cocaine hydrochloride (263) ( Figure 75) was analyzed by ECD, VCD, and ROA spectroscopies. The results showed that the solution structure was different from the crystal geometry.…”

Synthesis, enantioseparation, and absolute configuration assignment of iminoflavans by chiral high‐performance liquid chromatography combined with online chiroptical detection

“…Chiroptical detection for HPLC techniques on chiral stationary phases is particularly useful as a selective detection method for chiral molecules [9,10], and for enantiomeric purity determination [10,11]. Electronic circular dichroism (ECD) chiroptical technique lends itself to combining HPLC-ECD detection with several known procedures for predicting and interpreting ECD spectra, thus providing a practical method for the absolute configuration assignment of the separated enantiomers [9][10][11][12][13][14].…”