Development of synthetic methodologies: The aldol reactions of 1,3-dienolborinates, and the development and mechanistic study of aminolactonization

Reported herein is the development of the highly alpha-regio- and diastereoselective aldol reactions of vinylogous boron enolates. The action of dicyclohexylchloroborane, in combination with triethylamine on t-butyl but-3-enoate, has been demonstrated to furnish the anti-aldol adducts, whereas the reaction of methyl but-3-enoate with bis(exo-norbornyl)chloroborane in the presence of N,N-diisopropylethylamine furnishes the syn-isomers. Also presented is the design and synthesis of a library of alpha-methylene-gamma-butyrolactones which are highly potent in the inhibition of pancreatic cancer cell growth against three cell lines: Panc-1, MIA PaCa-2, and BxPC-3. Further described herein is the development of aminolactonization, a novel reaction that was discovered and developed as a means to provide direct access to alpha-(aminomethyl)-gamma-butyrolactones, the aminated derivatives of these compounds, which possess a wide range of activities. These compounds are synthesized in exceedingly high yields and excellent diastereoselectivities.