Since the past decades, the plant stilbenoid resveratrol has gained significant attention of the general public as well as the research community due to its versatile medicinal properties. Apart from resveratrol, there is also an increasing interest in other plant stilbenoids because of their different potential biological activities. In order to meet the increasing demand for stilbenoids, alternative and sustainable approaches for their production are needed. We identified the cytochrome P450 monooxygenase 154E1 from Thermobifida fusca YX (CYP154E1) which enables the synthesis of (E)‐4,4′‐dihydroxystilbene via direct double hydroxylation of (E)‐stilbene. The construction of a triple mutant led to a more than six‐fold increased catalytic efficiency compared to the wild type enzyme. CYP154E1 and variants thereof accepted not only (E)‐stilbene but also possessed remarkable activity towards ortho‐ and meta‐substituted hydroxystilbenes leading to resveratrol, (E)‐2,4′‐dihydroxystilbene, (E)‐2,4′,5‐trihydroxystilbene and (E)‐3,4′‐dihydroxystilbene. The combination of protein engineering and the use of methyl‐β‐cyclodextrin as substrate solubilizing agent resulted in product titers of up to 4.2 g L−1 and enzyme total turnover numbers (TTN) of up to 20,000.magnified image

The Masuda borylation/Suzuki arylation (MBSA) sequence starting from N‐protected 3‐iodoindoles has successfully been extended to the coupling of five‐membered heterocycles and indoles in the arylation step, which could not be achieved with previously developed MBSA methods. By this approach the one‐pot nature of the method as well as the use of a simple catalyst system has been retained. The applicability of the method has been demonstrated by the facile synthesis of camalexins and 3,3′‐biindoles, compounds of special interest due to their pronounced antifungal, antimicrobial and cytotoxic activities.

SummaryBased upon a consecutive one-pot Sonogashira–Glaser coupling–cyclization sequence a variety of 2,5-di(hetero)arylthiophenes were synthesized in moderate to good yields. A single Pd/Cu-catalyst system, without further catalyst addition, and easily available, stable starting materials were used, resulting in a concise and highly efficient route for the synthesis of the title compounds. This novel pseudo five-component synthesis starting from iodo(hetero)arenes is particularly suitable as a direct access to well-defined thiophene oligomers, which are of peculiar interest in materials science.

The Masuda borylation-Suzuki coupling (MBSC) sequence was successfully extended to the challenging coupling of vinylhalides with various (hetero)arylhalides using sterically hindered phosphane ligands. Starting from (hetero)arylhalides and α-bromocinnamaldehyde, the sequentially Pd-catalyzed process selectively furnishes α,β-substituted cinnamaldehydes without affecting the reactivity of the Michael system. These intermediates were implemented as entries into a novel synthesis of 3,4-diaryl 1H-pyrazoles in the fashion of a three-step one-pot procedure consisting of a Masuda borylation-Suzuki coupling and subsequent Michael addition-cyclocondensation-elimination sequence.

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