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A Chemo-Enzymatic Cascade Process for Single-Operation Synthesis of Chiral Aroma Lactones
Michael Schoen, Student, Vienna Institute of Technology
A combination of heterogeneous metal-catalyzed hydrogenation and enzymatic Baeyer-Villiger oxidation is chosen. In a continuous flow reactor, cheap dihydrojasmone is reduced to the saturated ketone with excellent diastereoselectivity (>90 % cis). Operation at high product concentration allows for direct introduction of the efflux to an efficient batch biotransformation (>7 g/L, <25 min), yielding natural (S,S)-Aerangis lactone in perfect purity (>99 % ee, >99 % de) via kinetic resolution by cyclododecanone monooxygenase (CDMO). By re-direction of the first product stream through a second flow reactor, diastereoselectivity is inverted in-line (90 % trans), giving access to epimeric (R,S)-Aerangis lactone with >99 % ee by employing cyclopentanone monooxygenase (CPMO) in the final biooxygenation.
A Non-Resonant Microwave Applicator for Continuous Flow Chemistry: Safe, Fast Optimization and Scale-Out Synthesis
Ashkan Fardost, Student, Uppsala University
The prospect of a microwave applicator fully dedicated to continuous flow
chemistry may offer many advantages over traditional heating methods, such as fast and
controlled heating at high temperatures, as well as a higher level of safety regarding
explosive reagents and pressure-producing reactions.
Synthetic protocols are hereby developed with a unique system utilizing a nonresonant
microwave heating applicator purpose-built for continuous flow that heats an
entire reactor without pronounced hot and cold spots, allowing method optimization in
small scale and subsequent scale-out without scale-up translation. With a pressure
resistance of up to 50 bars and volumes spanning the range of 160 µL (1 mm ID) to 6
mL (6 mm ID), the consumable glass reactors employed by the system allow a variety
of flow regimes, scales, as well as superheating of solvents.
The technology is demonstrated with method optimization and scale-out of classic
organic reactions including palladium-catalyzed organic transformations, synthesis of a
bioactive M. tuberculosis proteasome inhibitor, and Fischer indole synthesis with a
residence time of only 20 seconds, producing 34 grams of compound per hour (199
mmol/hour) with an isolated yield of 85%.
A Non-Resonant Microwave Applicator for Continuous Flow Chemistry: Safe, Fast Optimization and Scale-Out Synthesis
Ashkan Fardost, Student, Uppsala University
The prospect of a microwave applicator fully dedicated to continuous flow
chemistry may offer many advantages over traditional heating methods, such as fast and
controlled heating at high temperatures, as well as a higher level of safety regarding
explosive reagents and pressure-producing reactions.
Synthetic protocols are hereby developed with a unique system utilizing a nonresonant
microwave heating applicator purpose-built for continuous flow that heats an
entire reactor without pronounced hot and cold spots, allowing method optimization in
small scale and subsequent scale-out without scale-up translation. With a pressure
resistance of up to 50 bars and volumes spanning the range of 160 µL (1 mm ID) to 6
mL (6 mm ID), the consumable glass reactors employed by the system allow a variety
of flow regimes, scales, as well as superheating of solvents.
The technology is demonstrated with method optimization and scale-out of classic
organic reactions including palladium-catalyzed organic transformations, synthesis of a
bioactive M. tuberculosis proteasome inhibitor, and Fischer indole synthesis with a
residence time of only 20 seconds, producing 34 grams of compound per hour (199
mmol/hour) with an isolated yield of 85%.
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