Daniel R. Nicponski

Cu(II)-catalyzed olefin migration and Prins cyclization: highly diastereoselective synthesis of substituted tetrahydropyrans.

Metal-ligand complexes of Cu(OTf)(2) with an appropriate bisphosphine ligand have been shown to effectively catalyze the formation of substituted tetrahydropyrans via a sequential olefin migration and Prins-type cyclization. This methodology provides convenient access to a variety of functionalized tetrahydropyrans in excellent diastereoselectivities and good to excellent yields.

Synthetic α-(aminomethyl)-γ-butyrolactones and their anti-pancreatic cancer activities

Aminated α-methylene-γ-butyrolactones, which are readily synthesized with facile control of the diastereoisomerism, provide an economical and commercially-viable alternative to the use of aminated natural products. These aminoloactones, which exhibit excellent activity against three pancreatic cancer cell lines when measured at 10 μM-Panc-1, MIA PaCa-2, and BxPC-3-and are comparable to or better than parthenolide and dimethylaminoparthenolide (DMAPT, LC-1). It has also been shown that there is an effect on the biological activity depending on the identity of the amine.

Total regio- and diastereocontrol in the aldol reactions of dienolborinates.

It is reported that appropriate dienolborinates can provide access to both diastereomers of 2-(hydroxymethyl)but-3-enoates through exclusive α-regiocontrol in a non-vinylogous pathway. Contrary to previous reports in which dialkylchloroboranes failed to enolize propanoates, acidity-enhanced but-3-enoates readily undergo enolization, offering unprecedented control over the formation of these valuable synthons. The first example of an aldol reaction in the presence of a phosphine-borane adduct is also reported.

Diastereoselective Synthesis of Substituted Tetrahydropyrans by Copper(II)–Bisphosphine-Catalyzed Olefin Migration and Prins Cyclization

We developed a copper(II) triflate-bisphosphine complex catalyzed olefin migration and Prins cyclization which lead to the synthesis of substituted tetrahydropyran derivatives. The protocol is convenient and a variety of substituted tetrahydropyrans were obtained in good to excellent yields with excellent diastereoselectivities.

The first synthesis of a borylated α-methylene-γ-butyrolactone

BACKGROUND The Michael acceptor scaffolding is a source of rich biological activity for α-methylene-γ-butyrolactones and their derivatives. A wide variety of these structures are present in many natural products that are well-known for their useful medicinal properties. RESULTS The first example of a borylated α-methylene-γ-butyrolactone is presented herein, along with its antipancreatic cancer activities against Panc-1, MIA PaCa-2 and BXPC-3. The synthetic route chosen allows for a wide range of lactones to be synthesized through different cross-coupling reactions starting from arylic bromide precursors. The precursors were synthesized by way of a highly efficient, chemoselective and indium-promoted Barbier reaction. Specifically, the indium metal reacted with only one of two present bromide functionalities: an allylic bromide in the presence of an arylic one. The bromide precursors were also tested for activity in the same bioassay as the borylated lactone and parthenolide. CONCLUSION Notably, these brominated compounds demonstrate a significantly higher level of activity than parthenolide.