Configuration of the vitamin E analogue garcinoic acid extracted from garcinia kola seeds

Abstract

Vitamin E derivatives bearing a carboxylic group have recently gained great attention because of their antitumoral properties. Garcinoic acid (trans-13'-carboxy-delta-tocotrienol) is a vitamin E analog extracted from Garcinia Kola seeds in which the carboxylic group is at the end of the aliphatic side chain and reported to be a racemate based on the optical rotation measurements. However, CD determination of a sample of the acid analyzed by us gave a positive peak at 208 nm, indicating that it is not a racemate. To assess the enantiomeric composition of garcinoic acid, it was thus transformed to alpha-tocopherol and analyzed by chiral HPLC on column OD-H. On the basis of the elution order of alpha-tocopherol stereoisomers, the garcinoic acid sample resulted to be enantiopure with R configuration at carbon 2 of the chroman ring. Moreover, in a preliminary test, the acid and some of its derivatives showed a marked antiproliferative effect on glioma C6 cancer cells.

Extraction, purification and nuclear magnetic resonance (NMR) assignment of garcinoic acid from Garcinia kola (bitter kola) fruit

“…Our small negative specific optical rotation measurement {[] D -2.05 (c = 2.1, MeOH)} differs in both sign and in magnitude to the report from Maloney and Hecht (2005). However, it is consistent in magnitude with Terashima et al (1997) and in sign with Mazzini's et al (2009). In addition, since only one tocopherol cyclasebased biosynthetic pathway has been detailed, we are confident that the absolute stereochemistry of 5 is 2R, as shown in Figures 1 and 2.…”

“…Several heterocyclic compounds have been isolated from this source (Iwu and Igboko, 1982;Kabangu et al, 1987;Terashima et al, 1999) including -tocotrienoloic acid 5, which is also known as garcinoic acid (Delle Monache et al, 1984;Terashima et al, 1997;Terashima et al, 2002;Mazzini et al, 2009). Apart from its antioxidant (Terashima et al, 1997;Terashima et al, 2002) and DNA polymerase inhibition (Maloney and Hecht, 2005), numerous, mainly anecdotal, effects resulting from the ingestion of these nuts are appreciated by people using them (Adebisi and Song, 2008).…”

Complexity of vitamin E metabolism

“…As absolute concentrations of LCMs in the blood circulation of mammals are far too low for isolation, a natural compound, called garcinoic acid, isolated from the African bitternut Garcinia kola has proven to be a usefull resource to synthesize the α-and δ-LCMs of α-and δ-TOH [143] . Recent studies on α-and δ-LCMs have provided first preliminary insights [142,143,[256][257][258] into the molecular modes of action of the LCMs, which seem to be specific and distinct from that of their metabolic precursors. We therefore hypothesize that at least some of the discrepancies in the results obtained from in vitro and in vivo studies on vitamin E might be explained by individual differences in the physiological metabolism of vitamin E, and in particular under pathological conditions.…”

Human serum determination and in vitro anti-inflammatory activity of the vitamin E metabolite α-(13'-hydroxy)-6-hydroxychroman

“…Synthesis and characterization of LCMs were described in [12][13][14]. Vitamins and metabolites were stored in sealed amber vials under nitrogen at À 20°C until use.…”