Stereoselective Synthesis, Characterization, and Antibacterial Activities of Novel Isosteviol Derivatives with D‐Ring Modification

Abstract

Considerable interests have been attracted by isosteviol and its derivatives because of their large variety of bioactivities. In this project, a series of novel 15-and 16-substituted isosteviol derivatives were stereoselectively prepared by means of functional interconversions in ring D of the tetracyclic diterpene isosteviol. All compounds synthesized were characterized by analysis of NMR, IR, HR-MS data, and the configurations of 33 and 37 were confirmed by X-ray crystallographic analysis. The antibacterial activities in vitro of these isosteviol derivatives were investigated; the synthetic compounds were more active against Gram-positive than Gram-negative bacteria, and were especially active against Bacillus subtilis. Among them, compound 27 (MIC ¼ 1.56 mg/ml) exhibited the highest antibacterial activity and thus may be exploitable as a lead compound for the development of potent antibacterial agents.

Cytotoxic and Apoptosis‐Inducing Activities of Steviol and Isosteviol Derivatives against Human Cancer Cell Lines

“…On the other hand, treatment of 1 with NaIO 4 and KOH produces steviol (2; (5b,8a,9b,10a,13a)-13hydroxykaur-16-en-18-oic acid) [4], a kaurane-type diterpenoid which constitutes an aglycone moiety of 1. On the other hand, a number of derivatives of 2 and 19 have been prepared and evaluated for their bioactivities which included anti-inflammatory [7 -9], cytotoxic [10 -12], antibacterial [10] [13], glycosidase-inhibitory [14] [15], plantgrowth-regulation [16], antihyperglycemic [17], and glucocorticoid-agonist activities [18]. In addition, compounds 1, 2, and 19 have been suggested to be valuable chemopreventive agents against chemical carcinogenesis [5] [6].…”

“…To clarify the efficacy of the 13-OH group on the cytotoxicity, we prepared ent-kaur-16-en-19-ol 19-O-cinnamate (18), the 13-deoxy analog of 5, from ent-kaur-16-en-19-oic acid (15), which has been isolated previously from the pollen of Helianthus annuus [21]. ii) Benzyl chloride (BnCl)/pyridine; 9% (13). 16) and then reduced with LiAlH 4 to yield 17.…”

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

“…It has been shown that chemical transformations of the isosteviol core can be frequently performed in a stereoselective manner in the absence of any enantioselective catalysts or chiral auxiliaries [16,21]. The high stereoselectivity of those reactions can be attributed to the unique space structure of the rigid isosteviol skeleton with several chiral centers.…”

“…As a result, series of pyrazoline [15], pyrazole [15] and isoxazolidine [16] derivatives (Figure 1) have been recently synthesized.…”

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

“…(–)‐Isosteviol ( 2 ), being a metabolite of stevioside, also exhibits a wide range of biological activities, which might be the reason why the EU has reluctantly accepted stevioside as an alternative sweetener. Compound 2 can induce insulin regulation7 and exhibits cardioprotective8 as well as cytotoxic9 and antibacterial effects 10. During the past few years, (–)‐isosteviol has become a focus in organic chemistry for two major reasons.…”