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We have developed an efficient and straightforward methodology for the synthesis of novel tanshinone-substituted bis(indolyl/pyrrolyl)methane scaffolds 3 through TsOH catalysis-enabled addition of indoles or pyrroles 1 with tanshinones 2 based on molecular hybridization strategy. Products were smoothly obtained in good yields (up to 81% yield). This protocol also represents the first construction of tanshinone skeleton-fused bis(indolyl/pyrrolyl)methane scaffolds, thus leading to new knowledge in the fields of both molecular complexity and diversity-oriented synthesis and the lead compound discovery. Furthermore, their biological activities against human leukemia cells K562, human prostate cancer cells PC-3, and human lung cancer cells A549 have been preliminarily demonstrated by in vitro assays. The results demonstrated that most of these compounds 3 obtained by this protocol showed comparable activity to the positive control of cisplatin. [ABSTRACT FROM AUTHOR]

Reported is a facile and efficient methodology toward the synthesis of novel pyrimidine-fused spiropyrrolidine oxindoles via a multicomponent 1,3-dipolar cycloaddition reaction of pyrimidine-fused 3-alkenyloxindoles 1 with azomethine ylides (thermally generated in situ from sarcosine and formaldehyde). Products bearing adjacent quaternary–tertiary centers were smoothly obtained in high yields (up to 90% yield) with good diastereoselectivity (up to >20:1). In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human lung cancer cells A549, human prostate cancer cells PC-3, and human leukemia cells K562 by the MTT-based assays, using the commercially available broad-spectrum anticancer drug of Cisplatin as a positive control. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines of K562, PC-3, and A549, showed comparably potent or even more potent than the positive control of Cisplatin (up to 3.0 times), and indicated that novel pyrimidine-fused spiropyrrolidine oxindoles may be potential leads for further biological screenings and may generate drug-like molecules. [ABSTRACT FROM AUTHOR]

Developed herein was an expedient method toward the synthesis of pyrimidine-fused 3-alkenyloxindoles 4 via a Knoevenagel condensation/S N Ar sequential reaction of pyrimidine aldehydes 1 with 2-oxindoles 2 using alcohols 3 as both the solvents and the reactants. A wide variety of products, which is a typical hybridization of two key structural skeletons of 3-alkenyl-oxindole and pyrimidine found in an array of biologically active natural products and pharmaceutical compounds, were obtained smoothly with high efficiency (up to 93% yield) and high ( E/Z )-selectivities (up to >20:1 E/Z ). Furthermore, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays using the commercially available broad-spectrum anticancer drug Cisplatin as a positive control. These results suggested that most of pyrimidine-fused 3-alkenyloxindoles 4 showed equipotent or more potent than the positive control of Cisplatin (up to 5.1 times), which suggested that pyrimidine-fused 3-alkenyloxindoles 4 may be potential leads for further biological screenings. [ABSTRACT FROM AUTHOR]

Described herein is a facile and efficient methodology for diversity-oriented one-pot multicomponent synthesis of 3-aminomethyl quaternary carbon oxindole fused five-membered carbocyclic spirooxindoles 5 via knoevenagel condensation/Michael/cyclization and then aminomethylation reaction. A wide variety of products with varying degrees of substitution around it, were obtained smoothly with high efficiency (up to overall yield 73% and >20:1 diastereoselectivity). In particular, their biological activities against these three cell lines K562, A549 and PC-3 have been evaluated. These results suggested that most of 3-aminomethyl quaternary carbon oxindole fused five-membered carbocyclic spirooxindoles 5 showed equipotent or more potent than the positive control of Cisplatin (up to 3.4 times). [ABSTRACT FROM AUTHOR]

Developed herein is a facile and efficient methodology toward the synthesis of novel turmerone motif-fused spiropyrrolidine oxindoles via a multicomponent 1,3-dipolar cycloaddition event of dienones 2 with azomethine ylides (thermally generated in situ from isatin derivatives and sarcosine). Products bearing adjacent quaternary–tertiary centers were smoothly obtained in high yields (up to 93% yield) with good diastereoselectivity (up to >20:1). In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays, using the commercially available standard drug of Cisplatin as a positive control. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these two cell lines of K562 and A549, showed comparably potent or even more potent than the positive control of Cisplatin (up to 5.1 times), and indicated that novel turmerone motif-fused spiropyrrolidine oxindoles may be potential leads for further biological screenings and may generate drug-like molecules. [ABSTRACT FROM AUTHOR]

A facile and efficient methodology was developed for the synthesis of multifunctional polycyclic spiropyrrolidine oxindoles bearing mesityl oxide unit via a three-component 1,3-dipolar cycloaddition reaction of dienones 2 with azomethine ylides (thermally generated in situ from isatin derivatives and proline or thioproline). Products bearing adjacent four chiral carbon centers were smoothly obtained in high yields (up to 98% yield) with diastereoselectivities up to >20:1. Furthermore, the key structural characteristic of the products of such a reaction is the natural product ingredient turmerone motif fused at the 3-position of the spirooxindole core, with varying degrees of substitution around it. In addition, their biological activity has been preliminarily demonstrated by in vitro evaluation against human prostate cancer cells PC-3, human lung cancer cells A549 and human leukemia cells K562 by the MTT-based assays, using the commercially available standard drugs Cisplatin as a positive control. These results suggested there is a trend that lipophilicity groups improve the potency, and also suggested an mesityl oxide moiety located in the polycyclic spiropyrrolidine oxindoles is beneficial for the activity. The results also demonstrated that most of the compounds showed considerable cytotoxicities to these three cell lines K562, A549 and PC-3, and indicated that polycyclic spiropyrrolidine oxindole analogs bearing mesityl oxide unit may be potential leads for further antitumor activity screenings. [ABSTRACT FROM AUTHOR]