Xiong-Wei Liu

Efficient 1,6-addition reactions of 3-substituted oxindoles: Access to isoxazole-fused 3,3′-disubstituted oxindole scaffolds and hexahydro-1h-pyrido[2,3-b]indol-2-one scaffolds

ABSTRACT Developed herein is a new methodology for a hybrid of two pharmacophoric oxindole and isoxazole motifs to construct isoxazole-fused 3,3′-disubstituted oxindole scaffolds via an efficient 1,6-addition reaction of 3-substituted oxindoles to 3-methyl-4-nitro-5-alkenylisoxazoles, which might generate novel drug-like molecules for biological screenings. The method gives an easy access to a series of isoxazole-fused 3,3′-disubstituted oxindoles with 26 examples in high yields (up to 92% yield) and good diastereoselectivity (up to >20:1), which makes possible the synthesis of libraries under similar circumstances. Subsequently, a sequential Michael addition/amidation/reductive cyclization process was designed for accessing this hexahydro-1H-pyrido[2,3-b]indol-2-one scaffold, which is a key structural skeleton found in a large number of biologically active natural products and pharmaceutical compounds. Hexahydro-1H-pyrido[2,3-b]indol-2-one scaffold 7cg could be obtained in 42.5% overall yield after 4 steps. GRAPHICAL ABSTRACT

Diversity-oriented TsOH catalysis-enabled construction of tanshinone-substituted bis(indolyl/pyrrolyl)methanes and their biological evaluation for anticancer activities

ABSTRACT 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. GRAPHICAL ABSTRACT

Rapid, microwave-accelerated synthesis and anti-osteoporosis activities evaluation of Morusin scaffolds and Morusignin L scaffolds

Described herein is a facile and efficient methodology toward the synthesis of Morusin scaffolds and Morusignin L scaffolds 4-9 and 12via a novel three-step approach (Michael addition or prenylation, cyclization and cyclization) and use a rapid, microwave-accelerated cyclization as the key step. Furthermore, their biological activities have been preliminarily demonstrated by in vitro evaluation for anti-osteoporosis activity. These Morusin, Morusignin L and newly synthesized compounds 5b, 6a, 8e, 8f greatly exhibited the highest potency, especially at the 10-5mol/L (P<0.01), and had good in vitro anti-osteoporosis activities using the commercially available standard drug Ipriflavone as a positive control. The mechanisms associated with anti-osteoporosis effects of these compounds may be through the inhibition of TRAP enzyme activity and bone resorption in osteoclasts, and promotion effect of osteoblast proliferation in vitro. The results indicated that Morusin scaffolds and Morusignin L scaffolds may be useful leads for further anti-osteoporosis activity screenings.