Microthecaline A, a Quinoline Serrulatane Alkaloid from the Roots of the Australian Desert Plant Eremophila microtheca

Abstract

Chemical investigation of the roots of the Australian desert plant Eremophila microtheca yielded microthecaline A (1), a novel quinoline-serrulatane natural product. The structure of 1 was determined by spectroscopic analysis, and the absolute configuration was assigned by ECD. Compound 1 exhibited moderate antimalarial activity against Plasmodium falciparum (3D7 strain), with an IC of 7.7 μM. Microthecaline A represents the first quinoline-serrulatane alkaloid to be isolated from Nature.

Total synthesis of the plant alkaloid racemic microthecaline A: first example of a natural product bearing a tricyclic quinoline-serrulatane scaffold

“…Antonpaar-Monowave microwave synthesizer was used for reactions carried out under microwave conditions. 1 H NMR (500 MHz and 400 MHz) and 13 C (125 MHz and 100 MHz) spectra were recorded in CDCl 3 , DMSO-d 6 and CD 3 OD using (CH 3 ) 4 Si as internal standard. IR spectra were recorded as KBr plates on Shimadzu-IR Affinity instrument.…”

“…Column chromatography was performed on the crude compound using silica and 30% EtOAc/hexanes as the mobile phase afforded compound 2 (796 mg, 75%) as a light yellow solid (mp 99-101 C). 1…”

“…The product obtained was thoroughly characterized and the spectroscopic data was found to be comparable with the literature values available for microthecaline A (ESI). 1 Given the importance of enantiomeric purity to evaluate the biological activity of the molecule, attempts are currently underway in our lab to develop a synthetic route for (R)-microthecaline A, the naturally occurring stereoisomer (Scheme 4).…”

“…Column chromatography of the crude compound using silica and elution with 30% EtOAc/hexanes provided 3 (560 mg, 80%) as a light yellow solid (mp 70-72 C). 1 A mixture of 3 (500 mg, 1.45 mmol) and tri-uoromethanesulphonic acid (5 mL) were heated at 80 C for 2 hours. On completion, the reaction mixture was cooled to room temperature, diluted with ice cold water and quenched with saturated NaHCO 3 solution.…”

“…Isolation and characterization of the alkaloid (R)-microthecaline A was reported by Davis and co-workers from the Australian desert plant Eremophila microtheca. 1 The molecule is the rst example of a natural product bearing the tricyclic quinolineserrulatane scaffold and displayed moderate activity against 3D7 and Dd2 Plasmodium falciparum strains. Bioactive serrutalane based molecules are well known for their diverse activities including anti-tubercular, anti-inammatory and inhibition of phagocytosis.…”