Stereochemistry of Isoplagiochin C, A Macrocyclic Bisbibenzyl from Liverworts

Abstract

Cyclic bisbibenzyls, like isoplagiochins C (1) and D (2), are stereochemically intriguing molecules: Although not equipped with any of the traditional stereogenic elements that render molecules conformationally stable per se, they are sometimes isolated in an optically active form and are thus chiral at room temperature. The paper describes quantum chemical calculations, in particular investigations of the conformational space and molecular dynamics simulations, showing that the helicity is a property of the entire molecule, whose ring strain makes the molecule configurationally stable overall, with (formally) three stereogenic elements (two biaryl axes and one helical stilbene unit). Only one of the biaryl axes (the 'upper' one, joining C-12' and C-14) has a stable configuration, leading to a population of four interconverting diastereomers, yet without racemization at room temperature. On the basis of these conformational and dynamic calculations, the circular dichroism spectrum of isoplagiochin C (1) was calculated, leading to the first assignment of the absolute configuration of a cyclic bisbibenzyl. Accordingly, 1 has the P-configuration at the stereochemically stable biaryl axis and constitutes a mixture of diastereomers with respect to the other biaryl axis and the helical stilbene unit. From the temperature dependence of the racemization rates, an enantiomerization barrier of 101.6 kJ/mol was determined. Likewise, for the first time for cyclic bisbibenzyls, the enantiomeric ratio of this natural product was determined, by chromatography on a chiral phase with CD-coupling. Accordingly, 1 from Plagiochila deflexa is not enantiomerically pure, but occurs in a 85:15 ratio in favor of the enantiomer that has the P-configuration at the stereochemically stable axis.

Four New Sesquiterpenoids from the Fruits of Alpinia oxyphylla

“…10,11) The geometry was built on the basis of a S-configuration based on a 3D-structure of 2. Then, the conformational analysis was performed by means of the semiempirical PM3 method, as implemented in the program package QChem, starting from preoptimized geometries generated by the MM2 force-field in Chem 3D software.…”

“…The CH 2 Cl 2 extract was subjected to a silica gel column chromatography (CC) eluted with petroleum ether-acetone in a gradient (1 : 0 to 1 : 1), to afford 14 fractions (Fr. [1][2][3][4][5][6][7][8][9][10][11][12][13][14]. Fr.…”

Asymmetric Total Synthesis of Nigerone and ent‐Nigerone: Enantioselective Oxidative Biaryl Coupling of Highly Hindered Naphthols

“…On the other hand, the presence of a third band at 255 nm with a strong negative Cotton effect raised some uncertainty, making an independent interpretation of the experimental CD spectra of 24 by quantum chemical CD calculations [3][4][5] a rewarding task. Arbitrarily starting with the (P)-enantiomer of 24, a DFT (RI-BLYP/SVP) [15][16][17] based conformational analysis was performed.…”

“…In numerous cases such difficulties can be overcome by quantum chemical CD calculations. [3][4][5] One such class of compounds, the bisnaphthopyrone natural products, includes nigerone (1) and isonigerone (2) (Figure 1), [6] mold isolates that display moderate antitumor [7] and antibacterial [8] activities. While these compounds have been characterized, no total synthesis efforts have as yet appeared.…”

Novel Tirucallane‐Type Triterpenoids from Aphanamixis grandifolia

“…However, lack of proper model compounds for reference and absence of applicable exciton coupling in the CD spectrum of 1 rendered the assignment of its absolute configuration difficult by direct analysis of the CD curve [8]. Therefore, we calculated the electronic circular dichroism (ECD) by time-dependent density functional theory (TDDFT) [9] [10] and compared the result with experimental CD data of 1. The conformational analysis was performed by means of the semiempirical PM3 method, as implemented in the program package Q-Chem, starting from preoptimized geometries generated by the MM2 force field in Chem 3D software overlaid with key correlations observed in the ROESY spectrum.…”