Synthesis and antituberculosis activity of novel unfolded and macrocyclic derivatives of ent-kaurane steviol

(–)‐Isosteviol as a Versatile Ex‐Chiral‐Pool Building Block for Organic Chemistry

“…Various kinds of macrocycles have been synthesized based upon (–)‐isosteviol. For example, based upon the tweezer‐like structure 73 (Figure 7), closely related macrocycle 75 (Figure 8) can be obtained by two‐fold esterification with 1,3‐propanediol and malonyl chloride 70. It was found that 75 exhibits enhanced tuberculostatic activity, inhibiting the in vitro growth of Mycobacterium tuberculosis .…”

Synthesis of Macroheterocyclic Compounds with a Furan Bridge Possessing Structural Fragments of 1,2,3-Triazoles and Natural Diterpenoids

“…Glycyrrhetinic acidtweezer receptors with excellent selectivity and affinity for Hg 2+ ion, [11] and stable cyclic dimer based on oleanolic acid with remarkable binding ability to F -ion [7] were reported. In the series of macrocyclic diterpenoids from isosteviol [12,13] and steviol, [14] compounds with excellent antituberculosis activity were found. [14] Macrocyclic derivatives of diterpenoid paclitaxel exhibited cytotoxicity against pancreatic cell lines expressing multidrug-resistant genes.…”

“…In the series of macrocyclic diterpenoids from isosteviol [12,13] and steviol, [14] compounds with excellent antituberculosis activity were found. [14] Macrocyclic derivatives of diterpenoid paclitaxel exhibited cytotoxicity against pancreatic cell lines expressing multidrug-resistant genes. [15] In recent years, Cu I catalyzed azide-alkyne cycloaddition (CuAAC) received much attention as a method for construction of steroid/triterpenoid-based functional molecules.…”

Macrocyclic Derivatives of Diterpenoid Isosteviol with Hydrazide and Hydrazone Moieties

“…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.…”