Selective Hydroboration-Oxidation of Terminal Alkenes under Flow Conditions.

An efficient flow process for the selective hydroboration and oxidation of different alkenes using 9-borabicyclo(3.3.1)nonane (9-BBN) allows facile conversion in high productivity (1.4 g h-1 ) of amorpha-4,11-diene to the corresponding alcohol, which is an advanced intermediate in the synthesis of the antimalarial drug artemisinin. The in situ reaction of borane and 1,5-cyclooctadiene using a simple flow generator proved to be a cost efficient solution for the generation of 9-BBN.

Modular Chemoenzymatic Synthesis of Terpenes and their Analogues.

Non-natural terpenoids offer potential as pharmaceuticals and agrochemicals. However, their chemical syntheses are often long, complex, and not easily amenable to large-scale production. Herein, we report a modular chemoenzymatic approach to synthesize terpene analogues from diphosphorylated precursors produced in quantitative yields. Through the addition of prenyl transferases, farnesyl diphosphates, (2E,6E)-FDP and (2Z,6Z)-FDP, were isolated in greater than 80 % yields. The synthesis of 14,15-dimethyl-FDP, 12-methyl-FDP, 12-hydroxy-FDP, homo-FDP, and 15-methyl-FDP was also achieved. These modified diphosphates were used with terpene synthases to produce the unnatural sesquiterpenoid semiochemicals (S)-14,15-dimethylgermacrene D and (S)-12-methylgermacrene D as well as dihydroartemisinic aldehyde. This approach is applicable to the synthesis of many non-natural terpenoids, offering a scalable route free from repeated chain extensions and capricious chemical phosphorylation reactions.