Tamanu oil from Calophyllum inophyllum L. has long been used in traditional medicine. Ethanol extraction was found the best strategy for recovering bioactive compounds from the resin part of Tamanu oil, yielding two neutral and acidic resins fractions with high phenolics, flavonoids and pyranocoumarins concentrations. A further cascade of LPLC/HPLC separations of neutral and acidic resin fractions allowed identifying fifteen metabolites, and among them, calanolide D and 12-oxocalanolide A (both in neutral fraction) were first identified from a natural source. All these extracts, subfractions and isolated metabolites demonstrated increased free radical scavenging, antioxidant, anti-inflammatory, antimicrobial and antimycobacterial activity compared to Tamanu oil and its de-resinated lipid phase. Overall, these results could promote resinous ethanol-soluble Tamanu oil extracts as a useful multifaceted and renewable medicinal resource.

In order to discover new ³¹P NMR markers for probing subtle pH changes (<0.2 pH unit) in biological environments, fifteen new conformationally constrained or sterically hindered α-aminophosphonates derived from diethyl(2-methylpyrrolidin-2-yl)phosphonate were synthesized and tested for their pH reporting and cytotoxic properties in vitro. All compounds showed near-neutral pK_as (ranging 6.28–6.97), chemical shifts not overlapping those of phosphorus metabolites, and spectroscopic sensitivities (i.e., chemical shifts variation Δδ_ab between the acidic and basic forms) ranging from 9.2–10.7 ppm, being fourfold larger than conventional endogenous markers such as inorganic phosphate. X-ray crystallographic studies combined with predictive empirical relationships and ab initio calculations addressed the inductive and stereochemical effects of substituents linked to the protonated amine function. Satisfactory correlations were established between pK_as and both the 2D structure and pyramidalization at phosphorus, showing that steric crowding around the phosphorus is crucial for modulating Δδ_ab. Finally, the hit ³¹P NMR pH probe 1b bearing an unsubstituted 1,3,2-dioxaphosphorinane ring, which is moderately lipophilic, nontoxic on A549 and NHLF cells, and showing pK_a = 6.45 with Δδ_ab = 10.64 ppm, allowed the first clear-cut evidence of trans-sarcolemmal pH gradients in normoxic Dictyostelium discoideum cells with an accuracy of <0.05 pH units.