The first enantioselective total syntheses of prenylflavonoid Diels-Alder natural products (-)-kuwanon I, (+)-kuwanon J, (-)-brosimone A, and (-)-brosimone B have been accomplished from a common intermediate based on a concise synthetic strategy. Key elements of the synthesis include a biosynthesis-inspired asymmetric Diels-Alder cycloaddition mediated by a chiral ligand/boron Lewis acid, as we...

The combination of nucleophilic nitrenoids and ?-acid catalysis has emerged as a powerful tool in heterocycle synthesis. Accessing more varied heterocycle-substitution patterns by maintaining the same reaction pathways across different alkynes remains challenge. Here we show that Au(I) isoxazole-based with alkynyl thioethers provides controlled access to (3 + 2) annulation regioselective additi...

transforming relatively complex starting materials into substituted heterocycles, and for the functionalization of existing heterocycles, there is less precedent for methodology which involves the direct, regiodefined synthesis of highly substituted heterocycles from simple starting materials. As such, new methods for the synthesis of substituted heterocycles (or their precursors) are potential...

Novel strategies are developed for an efficient formal synthesis of (-)-mycalamide A. The left-hand side (-)-7-benzoylpederic acid is synthesized from (2S,3S)-2,3-epoxybutane. The key features include a highly regioselective Ru-catalyzed alkene-alkyne coupling reaction and a novel way to control the challenging C(7) stereocenter. The right-hand side was synthesized from (R)-pantolactone. The co...

The first stereoselective synthesis of lippidulcines A, B and C has been accomplished starting from (+)-hernandulcin, which has been prepared on a multigram scale. The previously assigned absolute configurations have been confirmed. The key steps of this synthesis are based on a modified version of the Kornblum-DeLaMare rearrangement, and on a highly regioselective and stereoselective ketone re...

The stereochemical determination of the potent antifungal agents leupyrrin A1 and B1 and the total synthesis of leupyrrin A1 are reported. The relative and absolute configuration was determined by a combination of high field NMR studies, molecular modeling, and chemical derivatization. The expedient total synthesis involves a one-pot sequential Zr-mediated oxidative diyne-cyclization/regioselec...

Regioselective sulfamoylation of primary hydroxyl groups enabled a 5-step synthesis (overall yield 17%) of the first reported small molecule inhibitor of sulfatase-1 and 2, ((2S,3R,4R,5S,6R)-4,5-dihydroxy-2-methoxy-6-((sulfamoyloxy)methyl)tetrahydro-2H-pyran-3-yl)sulfamic acid, which obviated the use of hydroxyl protecting groups and is a marked improvement on the reported 9-step synthesis (ove...

An efficient total synthesis of (+)-vincristine has been accomplished through a stereoselective coupling of demethylvindoline and the eleven-membered carbomethoxyverbanamine presursor. Demethylvindoline was prepared by oxidation of 17-hydroxy-11-methoxytabersonine, followed by regioselective acetylation with mixed anhydride method. Although an initial attempt of coupling by using demethylvindol...

Preparation of abasic site precursors through a divergent chemoenzymatic synthesis has been accomplished. Several biocatalysts and acylating agents were studied furnishing a practical and scalable green method useful for industrial applications. Highly regioselective acylation and deacylation reactions with 1,2-dideoxy-D-ribose are described resulting in excellent yield. A fast, atom-efficient ...

Starting from succinic anhydride and 2-methylanisole, a chemoenzymatic collective formal/total synthesis of several optically active tetrahydronaphthalene based bioactive natural products has been presented via advanced level common precursors; the natural product and antipode (-)/(+)-aristelegone B. Regioselective benzylic oxidations, stereoselective introduction of hydroxyl groups at the α-po...