Structural Elucidation of an Atropisomeric Entcassiflavan-(4β→8)-Epicatechin Isolated from Dalbergia monetaria L.f. Based on NMR and ECD Calculations in Comparison to Experimental Data

Abstract

A rare dihydoxyflavan-epicatechin proanthocyanidin, entcassiflavan-(4β→8)-epicatechin, was isolated from Dalbergia monetaria, a plant widely used by traditional people from the Amazon to treat urinary tract infections. The constitution and relative configuration of the compound were elucidated by HR-MS and detailed 1D- and 2D-NMR measurements. By comparing the experimental electronic circular dichroism (ECD) spectrum with the calculated ECD spectra of all 16 possible isomers, the absolute configuration, the interflavan linkage, and the atropisomers could be determined.

Keywords: Dalbergia monetaria; NMR; electronic circular dichroism (ECD); proanthocyanidin; procassidin dimer; quantum chemical calculation.

Scheme 1

Structure of compound 1 with axial position of the protons at C2, C4, and F2, as well as the OH group at F3, and the key HMBC correlations.

Scheme 2

Alternative structures of PA 1. (A) with C4–D8 and (B) with C4–D6 connectivity of the two ring systems.

Figure 1

(A) Calculated ECD spectrum (red curve) for the most stable conformation of the C4–D8 RRRR P atropisomer with a high similarity of 0.9674 and a shift of 19 nm to the experimental ECD-spectrum (black curve); the spectrum of the C4–D8 SSSS M enantiomer is shown by the blue curve, which does not fit. (B) Related structure with the dihedral angle (A10–C4–D8–D9) = 135.9°. (C) Calculated ECD spectrum (red curve) for the C4–D8 RRRR M atropisomer with a relative energy of 1.7 kcal/mol and a high similarity of 0.9642, but a high shift of 30 nm to the experimental ECD spectrum (black curve); the spectrum of the C4–D8 SSSS P enantiomer is shown by the blue curve, which does not fit. (D) Related structure with the dihedral angle (A10–C4–D8–D9) = −60.6°. Combining the Boltzmann weighted spectra of the most stable structures (RRRR P and RRRR M atropisomer) gives a ratio of P/M = 19:1 and a slightly increased similarity of 0.9682. However, the superimposed spectrum looks almost identical to that shown in Figure 1A.

Figure 2

(left) Calculated ECD spectrum (red curve) for the P atropisomer with a relative energy of 2.3 kcal/mol of the C4–D6 RRRR isomer (M isomer: see Figure S11) with a similarity of 0.9278 and a shift of 27 nm to the experimental ECD spectrum (black curve); (right) related structure with the dihedral angle (A10–C4–D6–D5) = −61.4°.