Semi-Synthesis structural elucidatio and in-vitro anti-snake venom activity of irregular monoterpenes derivatives from Baccharis trimera (Asteraceae)

ANA MARIA TORRES, GABRIELA RICCIARDI; MANUEL MINTEGUIAGA; CATALAN CESAR; DELLACASSA, EDUARDO

Sao Paulo

Congreso; 46th IUPAC World Chemistry Congress; 2017

IUPAC

Irregular monoterpenes are uncommon natural products found mainly in Asteraceae family, whose skeleton do not follow the Ruzicka rule, which establishes a head-to-tail fashion linkage between isoprene units resulting from biosynthesis1. Despite there are many ways to rearrange these building blocks, the o-menthane skeleton is very rare being only two natural base derivatives products known, both in Asteraceae: piquerol A from Piqueria trinervia and carquejol from Baccharis trimera (synonym of B. genistelloides)2. Usually, irregular monoterpenes have received interest as research targets for bioactivities (i.e.: pyrethrin insecticide compounds) by their reported ability to interact with biological systems1,2.The interaction of natural or natural-derived products with proteins is extremily important for snake venom inhibition, because many compounds can act inhibiting enzymes like phospholipases, proteases or coagulases blocking their activity and neutralizing their effects in vitro and in vivo3. Even when a neo-clerodane irregular diterpene found in B. trimera was cited with promissory anti-proteolytic and anti-hemorragic properties4, there is not previous reports on irregular monoterpene activity against snake venoms.In this carquejyl acetate (1) was isolated from B. trimera essential oil in order to obtain natural and synthetic derivatives [ carquejol (2), carquejone (3), 2-isopropenyl-3-methylphenol (?carquejyl phenol, 4) and 7,8-epoxy-carquejol (5)] following the scheme I. All products were purified by column chromatography (CC) and their structures established by 1D and 2D 1H-NMR, 13C-NMR and MS. The rearrangement of carquejone (3) to isocarquejone (6) was evidenced in the silica gel stationary phase during CC . Products 1-4, and the pure B. trimera essential oil, were tested by their in-vitro activity against Bothrops diporus and B. alternatus (Viperidae) venoms through SDS-PAGE, anti-hemolytic, anti-proteolytic and anti-coagulating techniques as reported by Camargo et al. 2011.3 The results showed some degree of activity for all compounds, but carquejone (3) was the most active one, demonstrating the relevance of employing semi-syntethic approachs in the searchof bioactive components.