Unfolded and macrocyclic ammonium derivatives of diterpenoids steviol and isosteviol having choline moieties. Synthesis and inhibitory activities toward acetylcholine- and butyrylcholinesterases

Abstract

Derivatives of isosteviol and steviol possessing choline moieties have been synthesized and assayed for AchE and BchE inhibitory activity.

Triphenylphosphonium Cations of the Diterpenoid Isosteviol: Synthesis and Antimitotic Activity in a Sea Urchin Embryo Model

“…8′-Bromo-3′,6′-dioxaoctan-1′-yl 16-oxo-ent-beyeran-19-oate 19-(9′-Triethylammonium-1′,4′,7′-trioxanonyl)-16,19-dioxo-entbeyerane bromide (17): This was synthesized as previously described: 60 Sea Urchin Embryo Assay. 44 Adult sea urchins, Paracentrotus lividus L. (Echinidae), were collected from the Mediterranean Sea on the Cyprus coast in March−April and November 2014 and kept in an aerated seawater tank.…”

Macrocyclic Derivatives of Diterpenoid Isosteviol with Hydrazide and Hydrazone Moieties

“…Then the solvent was removed under reduced pressure, a precipitate was recrystallized from methanol, dried in vacuo, and the pure product was obtained. 24,39,4,11,12,27,28,35,14,25,38(4α,16)tetra (19-nor-ent-beyerana)cyclooctatetracontaphane -2,5,10,13,16,23,26,29,34,37,40,47-dodecaone (16 (17). Anhydrous hydrazine (0.4 ml, 11 mmol) was added to the …”

“…Macrocycles having such structures were obtained with the help of synthesis only. Thus macrocycles synthesized on the basis of monoterpenes (myrtenal, [8] 3-carene, [9,10] α-pinene [9,10] ), diterpenoids (isosteviol, [11][12][13][14] steviol, [15] paclitaxel [16,17] ), and bile acids [18,19] have been reported. In these compounds mono-or polycyclic terpene, or steroide skeletons are combined in macrocycle by various linkers.…”

“…Two isosteviol molecules were first bonded via the oxo groups into binuclear isosteviol derivative possessing an unfolded structure, and its macrocylization was realized in the last step. [13,15] Continuing the series of papers concerned with syntheses of macrocyclic isosteviol derivatives, in which isosteviol moieties were connected by various diester linkers, [10][11][12][13][14] herein we report the synthesis of macrocyclic isosteviol derivatives having hydrazide and hydrazone fragments. It was found previously that the combination of two isosteviol molecules with diester linker increased its antituberculosis activity by several times, and the greater is the distance between isosteviol moieties, the greater is the activity.…”

Synthesis and Anticancer Evaluation of Complex Unsaturated Isosteviol-Derived Triazole Conjugates

“…In particular, since the end of the 1990s, ent-beyrane diterpenoid isosteviol has attracted a great deal of attention from medicinal chemists as a native scaffold for organic chemistry and drug discovery [1][2][3]. With its unique rigid skeletal structure with six stereo centers, isosteviol derivatives have been shown to have numerous biological activities [4][5][6][7][8][9], particularly in the anticancer area [10][11][12][13][14][15].…”