Synthesis of oxygenated oleanolic and ursolic acid derivatives with anti-inflammatory properties

Abstract

The scalable syntheses of four oxygenated triterpenes have been implemented to access substantial quantities of maslinic acid, 3-epi-maslinic acid, corosolic acid, and 3-epi-corosolic acid. Semi-syntheses proceed starting from the natural products oleanolic acid and ursolic acid. Proceeding over five steps, each of the four compounds can be synthesized ongram scale. Divergent diastereoselective reductions of α-hydroxy ketones provided access to the four targeted diol containing compounds from two precursors of the oleanane or ursane lineage. These compounds were subsequently evaluated for their ability to inhibit inflammatory gene expression in a mouse model of chemically induced skin inflammation. All compounds possessed the ability to inhibit the expression of one or more inflammatory genes induced by 12-O-tetradecanoylphorbol-13 acetate in mouse skin, however, three of the compounds, corosolic acid, 3-epi-corosolic acid and maslinic acid were more effective than the others. The availability of gram quantities will allow further testing of these compounds for potential anti-inflammatory activities as well as cancer chemopreventive activity.

Combinatorial treatment with natural compounds in prostate cancer inhibits prostate tumor growth and leads to key modulations of cancer cell metabolism

“…Betulinic acid, caffeic acid phenylethyl ester, genistein, palmatine chloride, shikonin and RES were purchased from CaymanChemicals (Ann Arbor, MI, USA), whereas >98% pure corosolic acid, epi-maslinic acid, epi-UA, epi-corosolic and maslinic acid were prepared as recently described. 58 , 59 For all screens, cells in exponential proliferation were seeded in 384-well plates using a Viaflo Assist micro-plate dispenser (Integra Biosciences, Hudson, NH, USA) and allowed to adhere overnight. During the primary screening, HMVP2 cells were screened with the individual NCL compounds at 3 time-points (12, 24 or 48 h) and three doses (5, 10, 20 µM final concentration).…”

Preparation and antitumor evaluation of self-assembling oleanolic acid-loaded Pluronic P105/D-α-tocopheryl polyethylene glycol succinate mixed micelles for non-small-cell lung cancer treatment

“…Oleanolic acid (OA; Figure 1) is a natural product with potential antitumor activity and can induce apoptosis in many tumor cell lines, including those of the breast, lung, and liver. [3][4][5] Unfortunately, the poor water solubility and low permeability of OA have limited its use. 6 Therefore, it is necessary to select an appropriate nano-drug delivery system to increase the solubility of OA and to reduce the oral first pass effect and improve bioavailability.…”

Evaluation of pentacyclic triterpenes found inPerilla frutescensfor inhibition of skin tumor promotion by 12-O-tetradecanoylphorbol-13-acetate

“…UA and OA were purchased from Sabinsa Company (East Windsor, NJ) and Stanford Chemicals (Irvine, CA), respectively. AA, CA, MA, 3-epiCA, and 3-epiMA were prepared as recently described by us [ 61 ]. All triterpenes used in the current experiments were > 98% pure.…”