Abstract
1H NMR-guided fractionation of the petroleum ether extract of the aerial parts from Hypericum hirsutum yielded to the isolation of 19 polyprenylated polycyclic acylphloroglucinols. Structure elucidation based on 1D and 2D NMR spectroscopy together with high-resolution electrospray ionization mass spectroscopy revealed 14 acylphloroglucinols with a homoadamantane scaffold (1–14), while 5 further compounds showed an adamantane skeleton (15–19). Except for hookerione C (15), all isolated metabolites are hitherto unknown. While structurally-related metabolites have been isolated from other Hypericum species, it is the first report of admantan and homoadamantan type acylphloroglucinols in section Taeniocarpium Jaub. & Spach (Hypericaceae). The isolated compounds have been tested in a crystal violet-based in vitro assay on their properties to reduce the proliferation of human microvascular
endothelial cells compared to hyperforin as the positive control. They showed a moderate reduction of proliferation with IC50 values in the range ~ 3 – 22 µM, with the homoadamantane-based compounds 2 and 4 being the most active. In addition, inhibition of the TNF-α-induced ICAM-1 expression was determined for 1 – 5, 7, and 10 – 12. Substances 3 and 12 reduced the ICAM-1 expression significantly (to 46.7% of control for 3, 62.3% for 12, at 50 µM).
The synthesis of 5-diazo-5-[13C]-homoadamantan-4-one (12) is achieved by ring expansion of adamantanone with 13C-labelled diazomethane, conversion of the resulting 4-[13C]-homoadamantan-4-one (10) to the hydroxymethylene compound (11), followed by deformylative diazo group transfer reaction. The photolysis of 12 with pyrex filtered UV-light in dioxane-water (10:1) yields adamantan-2-carboxylic acid containing all the label in the 2-position of the adamantane skeleton. The total absence of isotope scrambling excludes the intermediate formation of the polycyclic oxiren (16) (Scheme 3).
The crystals of 1-methylsulfonyladamantane are monoclinic, space group P21/a, with a = 11.094(3), b = 7.668(2), c = 13.161(3) Å, β = 101.74(2)0, V = 1 096.1(5) Å3, Z = 4, Dx = 1.29 g cm -3, MoKα, λ = 0.71069 Å, μ = 2.65 cm-1, F(000) = 456, T = 291 K, the final R value is 0.036 for 1 834 observed reflections. For this compound and from literature data, the bond angles of adamantane derivatives are briefly discussed: the angle on the substituted C(1) atom depends clearly on the substituent but the available figures are still rather imprecise.
The 13C NMR spectra of all monohydroxy and ditopic dihydroxy adamantane isomers were measured and the lines assigned. The numbers of the isomers and of the non-equivalent carbon atoms permitted a verification of the simple additivity of the shielding contributions of two hydroxyl groups on the rigid adamantane skeleton in the isomers without a possibility of a direct OH-OH interaction. If such interactions occur, deviations are found. The direction and magnitude of the deviations is in agreement with the current interpretation of 13C chemical shifts in other classes of cyclic compounds. It is concluded that the deviations are not caused by intramolecular hydrogen bonds. The deviations and the values of substituent chemical shifts offer some limited information about the origin of the shielding effects, especially of those dependent on stereochemistry and degree of substitution (γanti effect).
Abstract Hydroboration of CS2 with NaB3H8 yields the new compound Na[CH2(BH 2)5S4 ], isolated as the tri-dioxanat. The anion has the adamantane skeleton CB5S4 .The crystal structure of the analog-ous compound (C6H5)4P[CH2 (BH2)5 S4 ] was determined from diffractometer data and refined to R = 0.043. The tetragonal unit cell (space group P4/n) contains two formula units (a = b = 1351.7 pm; c = 790.0 pm).
Hydration of Adamantane Skeleton: Water Assembling around Amantadine and Halo-substituted Adamantanes