New malonate macrocycle bearing two isosteviol moieties and its adduct with fullerene C60

Macrocyclic Derivatives of Diterpenoid Isosteviol with Hydrazide and Hydrazone Moieties

“…105-110 °C [20] ). Acid chloride 12 was synthesized from diacid 10 by a facile rout [13] as an oil that was immediately used in the reactions with adipic acid dihydrazide and hidrazine. Adipic acid dihydrazide was purchased from Alfa Aesar (Massachusetts, USA).…”

“…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.…”

“…Some of its derivatives were used as starting compounds: isosteviol oxo group was selectively reducted, or the carboxyl group was converted into the carbonyl chloride group, or into the hydroxymethyl group. [12,13] The synthetic potential of directly the C 16 =O group of isosteviol was not realized, though the involving this functionality in reactions with amines should lead to nitrogen containing macrocycles which could exhibit any biological activities. In addition, the course of a macrocyclization reaction of isosteviol derivative bearing the C 16 OH and the C 4 CH 2 OH groups with chloride-anhydrides of dicarboxylic acids appeared to be dependent on their length.…”

“…[20] The macrocyclization of this acid into a macrocycle of c kind (Scheme 1c) resulted in the further increase in bioactivity. [13] We have revealed that some binuclear isosteviol derivatives having an unfolded molecular structure, in which isosteviol moieties † Minimal inhibitory concentration Scheme 1. Schematic representation of macrocyclic terpenoids.…”

“…[21] Taking into account results aforementioned [13,20] we suppose that a synthesis of macrocycles having several isosteviol moieties connected by dihydrazide and dihydrazone linkers could be an efficient approach to obtain novel isosteviol derivatives exhibiting higher antituberculosis activities.…”