Total Syntheses of the Isomeric Aglain Natural Products Foveoglin†A and Perviridisin†B: Selective Excited-State Intramolecular Proton-Transfer Photocycloaddition.

Selective excited-state intramolecular proton-transfer (ESIPT) photocycloaddition of 3-hydroxyflavones with trans, trans-1,4-diphenyl-1,3-butadiene is described. Using this methodology, total syntheses of the natural products (±)-foveoglin A and (±)-perviridisin B were accomplished. Enantioselective ESIPT photocycloaddition using TADDOLs as chiral hydrogen-bonding additives provided access to (+)-foveoglin A. Mechanistic studies have revealed the possibility for a photoinduced electron-transfer (PET) pathway.

Biomimetic kinetic resolution: highly enantio- and diastereoselective transfer hydrogenation of aglain ketones to access flavagline natural products.

We have previously reported asymmetric syntheses and absolute configuration assignments of the aglains (+)-ponapensin and (+)-elliptifoline and proposed a biosynthetic kinetic resolution process to produce enantiomeric rocaglamides and aglains. Herein, we report a biomimetic approach for the synthesis of enantiomerically enriched aglains and rocaglamides via kinetic resolution of a bridged ketone utilizing enantioselective transfer hydrogenation. The methodology has been employed to synthesize and confirm the absolute stereochemistries of the pyrimidone rocaglamides (+)-aglaiastatin and (-)-aglaroxin C. Additionally, the enantiomers and racemate of each metabolite were assayed for inhibition of the heat-shock response, cytotoxicity, and translation inhibition.

Remodeling natural products: chemistry and serine hydrolase activity of a rocaglate-derived ß-lactone.

Flavaglines are a class of natural products with potent insecticidal and anticancer activities. ß-Lactones are a privileged structural motif found in both therapeutic agents and chemical probes. Herein, we report the synthesis, unexpected light-driven di-epimerization, and activity-based protein profiling of a novel rocaglate-derived ß-lactone. In addition to in vitro inhibition of the serine hydrolases ABHD10 and ACOT1/2, the most potent ß-lactone enantiomer was also found to inhibit these enzymes, as well as the serine peptidases CTSA and SCPEP1, in PC3 cells.

Enantioselective photocycloaddition of 3-hydroxyflavones: total syntheses and absolute configuration assignments of (+)-ponapensin and (+)-elliptifoline.

We have previously reported development of biomimetic, asymmetric [3 + 2] photocycloadditions between 3-hydroxyflavones and cinnamate dipolarophiles to access (-)-rocaglamide and related natural products. Herein, we describe enantioselective syntheses of aglain cycloadducts leading to the first total syntheses and absolute configuration assignments of the aglain natural products (+)-ponapensin and (+)-elliptifoline.

Chiral anthracene and anthrone templates as stereocontrolling elements in Diels-Alder/retro Diels-Alder sequences.

The development of chiral anthracene templates for use in Diels-Alder/retro Diels-Alder sequences is described. A summary of past results and new progress is reported.

A new chiral anthracene for the asymmetric Diels-Alder/retro-Diels-Alder sequence.

(-)-(R)-9-(1,2-Dimethoxyethyl)anthracene (8) is successfully employed as a chiral template in the Diels-Alder/retro-Diels-Alder sequence for the preparation of alpha,beta-unsaturated lactams. The cycloadditions proceed with complete diastereoselectivity, and regioselectivity in subsequent transformations of the carbonyl groups is also excellent. Flash vacuum pyrolysis accomplishes the cycloreversion.