Butyrolactone synthesis via polar radical crossover cycloaddition reactions: diastereoselective syntheses of methylenolactocin and protolichesterinic acid.

A direct catalytic synthesis of γ-butyrolactones from simple alkene and unsaturated acid starting materials is reported. The catalytic system consists of the Fukuzumi acridinium photooxidant and substoichiometric quantities of a redox-active cocatalyst. Oxidizable alkenes such as styrenes and trisubstituted aliphatic alkenes are cyclized with unsaturated acids via polar radical crossover cycloaddition (PRCC) reactions. This method has been applied to the diastereoselective total synthesis of methylenolactocin and protolichesterinic acid.

Synthesis of cyclobutane lignans via an organic single electron oxidant-electron relay system.

A direct method to synthesize lignan cyclobutanes and analogs via photoinduced electron transfer is presented. A variety of oxygenated alkenes are employed to furnish terminal or substituted cyclobutane adducts with complete regiocontrol, yielding cycloadducts with trans stereochemistry. Key to minimizing competing cycloreversion is the inclusion of an aromatic electron relay (ER). This method has been adapted to the synthesis of the natural products magnosalin and pellucidin A.

Suzuki-Miyaura coupling of aryl carbamates, carbonates, and sulfamates.

The first Suzuki-Miyaura cross-couplings of carbamates, carbonates, and sulfamates is described. The method provides a powerful means of using simple derivatives of phenol as precursors to polysubstituted aromatic compounds, as exemplified by a concise synthesis of the anti-inflammatory drug flurbiprofen.

Using enzyme assays to evaluate the structure and bioactivity of sponge-derived meroterpenes.

Enzyme screening of crude sponge extracts prioritized a 2005 Papua New Guinea collection of Hyrtios sp. for further study. The MeOH extract contained puupehenone and four puupehenone analogues (1, 2, 3, 5, and 7) along with a new diastereomer, 20-epi-hydroxyhaterumadienone (4), and a new analogue, 15-oxo-puupehenoic acid (6). The drimane terpene core of 4 and 6 was rapidly dereplicated, and the modified Mosher's method identified 4, while 1D and 2D NMR techniques were used to solve 6. These compounds plus noteworthy repository natural products and standards were tested against three lipoxygenase isozymes, human 5-, 12-, and 15-lipoxygenases. Significant potency and selectivity profiles were exhibited in the human 5-lipoxygenase assay by puupehenone (1) and jaspaquinol (9) and structural factors responsible for activity identified.