Diastereoselective synthesis of α-(aminomethyl)-γ-butyrolactones via a catalyst-free aminolactonization.

An auto-catalytic domino reaction, presumably involving an aza-Michael reaction, proton transfer, and lactonization, furnishing α-(aminomethyl)-γ-butyrolactones in near quantitative yields and excellent diastereoselectivity is described.

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.

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.

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.

A Tandem Olefin Migration and Prins Cyclization Using Cu(OTf)(2)-Bisphosphine Complexes: An Improved Synthesis of Functionalized Tetrahydropyrans.

In situ-generated (bis-DPPMB)-Cu(OTf)(2) complex has been examined to catalyze a tandem olefin migration and Prins cyclization of an alkenol with various aldehydes. The reaction proceeded with electron-rich aromatic aldehydes at room temperature and provided functionalized tetrahydropyrans in good yields. An efficient synthesis of the bis-DPPMB ligand has also been described.

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.