Preparative chiral separation and absolute configuration of the synthetic pterocarpanquinone LQB‐118

Abstract

The racemic pterocarpanquinone LQB-118 is active, in mice and hamsters, against tegumentary and visceral leishmaniasis. This compound also presents antiinflammatory and antineoplastic activity in mice. The low level of toxicity observed in these studies makes LQB-118 a promising drug candidate. In order to conduct further biological testing to investigate enantioselectivity in the above-mentioned activities, a multimilligram amount of each enantiomer of LQB-118 was produced. Furthermore, vibrational circular dichroism (VCD) and Density Functional Theory (DFT) calculations were used to determine unambiguously their absolute configurations. The comparison of experimental and calculated VCD data led to the assignment of (-)-LQB-118 as 7aR,12aR and, consequently, (+)-LQB-118 as 7aS12aS.

Vibrational Circular Dichroism for the Assignment of Absolute Configuration of Natural Products in Brazil

“…In this section, we will present a list of natural products and related compounds studied by Brazilian researchers (Table S1), which had their absolute configuration assigned using VCD spectroscopy and DFT calculations, associated or not with other techniques (Batista Jr et al 2011b;2013;2015b;Batista et al 2019;Caldas et al 2020;Caleffi et al 2019;Canzi et al 2018;Covington et al 2016;Demarque and Merten 2017;Felippe et al 2012;Gimenes et al 2019;Joseph-Nathan et al 2010;Lianza et al 2020;Londero et al 2021;Medina et al 2019;Morais et al 2020;Ortega et al 2017;Ortega et al 2018;Ortega et al 2019;Queiroz et al 2019;Rodriguez et al 2020;Santos Jr et al 2014;Scatena et al 2017;Socolsky et al 2012;Souza et al 2019;Teodoro et al, 2018a;2018b). Some selected examples will be discussed in detail below.…”

Enantiomeric Mixtures in Natural Product Chemistry: Separation and Absolute Configuration Assignment

“…To avoid immiscibility problems with the eluents, one should go first to 100% EtOH. Methanol (MeOH) or acetonitrile (ACN) are the solvents of choice, or mixtures of them [ 55 , 84 ]. Reversed elution mode should also be explored.…”

New Levan-Based Chiral Stationary Phases: Synthesis and Comparative HPLC Enantioseparation of (±)-trans-β-Lactam Ureas in the Polar Organic Mode

“…The polar organic mode is particularly attractive for the analytical and preparative separation of enantiomers, as it offers several advantages, such as a shorter analysis time, high efficiency, better signal/noise ratio, usually higher solubility of the analytes in the mobile phase, etc. [39][40][41][42]. In the polar organic mode, only polar organic solvents (except water), usually alcohol (methanol, ethanol, and 2-propanol), acetonitrile, or their combinations are used as the mobile phase [39][40][41].…”