Uncommon Reactivity of a Seco-Oxacassane Diterpenoid and Antiproliferative Activity of Some Derivatives

Abstract

The main diterpenoid of Acacia schaffneri, 7,8-seco-7,8-oxacassa-13,15-dien-7-ol-17-al (1), has two aldehydes of which one is protected as a ε-lactol.The free aldehyde resisted to afford the carboxylic acid using reagents with different oxidative strength, although 1 gave oxime 2 when treated with hydroxylamine, β-hydroxyketone 3 after addition of acetone, aldo-ε-lactone 4 whereby only the lactol was oxidized when using Jones reagent, and epoxyformate 5 after Baeyer-Villiger treatment. Hydrolysis of 5 with NaHCO3 gave 6. Structures 2-6 followed from physical and spectral data including X-ray diffraction. All compounds showed antiproliferative activity similar to some chemotherapeutic drugs against C2C12, L929, SiHa, and MDA-MB-231 cell lines. RESULTS AND DISCUSSIONDiterpenoid 1 was obtained in adequate amounts for the preparation of 2-6 from the aerial parts of A.schaffneri. 1 Nucleophilic addition of hydroxylamine to 1 gave 2 in 66% yield, while aldol condensation of 1 with acetone in basic medium led to β-hydroxyketone 3 in 43% yield. The corresponding 1 H NMR spectra did not evidence both syn and anti oximes for 2, nor the absolute configuration (AC) of C-17 in the case of 3. However, the anti oxime geometry in 2 and the (17S) AC in 3 followed from the X-ray diffraction (XRD) studies detailed below. Although 3 was not the only expected condensation product, the γ,δ-unsaturated carbonyl compound could not be obtained even when using large excesses of acetone and NaOH.