Acyclic Remote 1,6-Stereoselection.

Stereochemical communication in homopropargylation and homoallylation of aldehydes was achieved by the Ti-O temporary linker strategy. Propargylic and allylic alcohol derivatives were employed as convenient pronucleophiles, obviating prefabrication of propargylation/allylation reagents. It was surprising that 1,6-diastereoselectivity was affected by not only the Grignard reagent but also the reaction solvent.

Cananginone Abrogates EMT in Breast Cancer Cells through Hedgehog Signaling.

Cananginones, a family of linear acetogenins found as secondary metabolites in the plant kingdom, show cytotoxicity against several types of cancer cells. We aimed to investigate the efficacy of cananginone and its mechanism as an anti-cancer agent. Our initial screening of Cananginone against HepG2, PC3, A549, and MCF7 cells showed anti-cancer activities and is more potent against MCF7 cells, consistent with the previous report. Next, cell-based assays have revealed that cananginone abrogates cancer stem cell renewal as well as Epithelial-Mesenchymal Transition (EMT) and increased the ROS level beyond the threshold level thus reducing the viability of cancer cells. In the connection of Hh-Gli to EMT, our study indicated that cananginone inhibits Gli1 in a non-canonical pathway. Presumably, this is the first report on the inhibitory activity of cananginone in the Hh pathway and is different from Hh-antagonists cyclopamine and GANT 61 considering the mechanism.

Studies toward the synthesis of strevertenes A and G: stereoselective construction of C1-C19 segments of the molecules.

Stereoselective synthesis of common C1-C19 skeletons of pentane macrolides strevertenes A and G possessing 10 stereogenic centers has been achieved using a flexible and convergent strategy. The salient features of this synthetic study include the Evans aldol reaction for the constructions of C2, C3, C13, and C14 centers, CBS reduction for the generation of a C7 center, Hoveyda-Grubbs cross olefin metathesis for the synthesis of C8-C9 bond, and Wittig olefination for the installation of C16-C19 conjugated olefins.

Studies Directed toward the Stereoselective Synthesis of Cytospolide E.

Our exhaustive effort toward the total synthesis of cytotoxic marine nonanolide cytospolide E has been detailed. To achieve this synthesis, we have explored both the ring-closing metathesis and lactonization-based macrocyclization strategies using a variety of precursors. Unfortunately, none of them provided the desired product. The ring-closing metathesis approach provided mainly the macrocycle with Z-olefin, whereas the macrolactonization strategy culminated in 8-epi-9-epi-cytospolide E following the regioselective formation of a 10-membered macrocycle over a 9-membered macrocycle.

Stereoselective Total Synthesis of Carolacton.

A short and convergent strategy for the stereoselective total synthesis of biologically active natural product carolacton has been accomplished. Our synthesis highlights the Urpi acetal aldol, Crimmins aldol, Ireland-Claisen rearrangement, TiCl4-assisted aldol followed by ß-hydroxy elimination to construct C7-C8 olefin, and ring-closing metathesis as the key steps for achieving the target molecule with an overall yield of 18.8%.

Total synthesis of cananginone C and structural revision of debilisone A.

A short, convergent and general strategy for stereoselective total synthesis of biologically active α-substituted γ-hydroxymethyl γ-lactone based natural products cananginone C and debilisone A has been developed. The salient features of this synthesis include Cadiot-Chodkiewicz coupling, Evans allylation, Sharpless asymmetric dihydroxylation and γ-lactonization. The originally proposed structure of debilisone A has been revised.

Asymmetric Total Synthesis of Bioactive Natural Lipid Mycalol.

A concise and convergent route for stereoselective total synthesis of promising anticancer natural lipid mycalol has been achieved using cheap and readily available l-arabinose as a chiral pool. The notable features of our synthesis comprised regioselective Wacker oxidation, Sharpless asymmetric dihydroxylation, Julia-Kocienski olefination, Wittig olefination, Zipper reaction, and Sonogashira reaction. Comparison of the spectroscopic data on a series of isomers supports the revised structure (Org. Lett. 2015, 17, 1652) instead of the one originally proposed.