Total Synthesis of Capsaicin Analogues from Lignin‐Derived Compounds by Combined Heterogeneous Metal, Organocatalytic and Enzymatic Cascades in One Pot

Abstract

The total synthesis of capsaicin analogues was performed in one pot, starting from compounds that can be derived from lignin. Heterogeneous palladium nanoparticles were used to oxidise alcohols to aldehydes, which were further converted to amines by an enzyme cascade system, including an amine transaminase. It was shown that the palladium catalyst and the enzyme cascade system could be successfully combined in the same pot for conversion of alcohols to amines without any purification of intermediates. The intermediate vanillyl-A C H T U N G T R E N N U N G amine, prepared with the enzyme cascade system, could be further converted to capsaicin analogues without any purification using either fatty acids and a lipase, or Schotten-Baumann conditions, in the same pot. An aldol compound (a simple lignin model) could also be used as starting material for the synthesis of capsaicin analogues. Using l-alanine as organocatalyst, vanillin could be obtained by a retro-aldol reaction. This could be combined with the enzyme cascade system to convert the aldol compound to vanillylamine in a one-step onepot reaction.Capsaicin (7a) is a pungent compound found in Capsicum spp, and is responsible for the hot and spicy

Selective Access to All Four Diastereomers of a 1,3‐Amino Alcohol by Combination of a Keto Reductase‐ and an Amine Transaminase‐Catalysed Reaction

“…Neither the ( S )‐selective ATA from Chromabacterium violaceum (ATA‐Cvi) and its mutant W60C,18 nor six ( R )‐selective ATAs led to a conversion when combined with a large alanine excess (80–200 equiv., see Supporting Information, Table S1 for tested enzymes). Also, when combined with an enzyme cascade ( L ‐alanine dehydrogenase and glucose dehydrogenase19) to shift the equilibrium, ATA‐Cvi did not yield the desired amino alcohol. However, benzylamine was formed as a side‐product with conversions up to 52% (HPLC Method 1, see Supporting Information for all analytics).…”

Integrated Heterogeneous Metal/Enzymatic Multiple Relay Catalysis for Eco-Friendly and Asymmetric Synthesis

“…[5][6][7] The inclusion of heterogeneous catalysis is highly desirable since it would allow for different reactivity not possible using homogeneous organometallic catalysts (e.g reductions and oxidations) and allow for facile removal and recycling of the transition metals. 8 It can also be implemented in flow-chemistry processes.…”

The Impact of Recent Developments in Technologies which Enable the Increased Use of Biocatalysts

“…In an excellent example of the flexible use of multiple biocatalysts, Berglund et al reported a total synthesis of capsaicin analogues from a primary alcohol 47 using a metal‐catalyzed oxidation to produce aldehyde 48 , followed by a one‐pot amine transaminase‐catalyzed reductive amination and a lipase‐catalyzed amidation, using a fatty acid as the acyl donor (Scheme ) . The authors initially investigated the use of a biocatalyzed oxidation, which could be coupled with the amine transaminase; the alcohol dehydrogenase could function as a redox partner for the regeneration of cofactors for the l ‐alanine dehydrogenase ( l ‐AlaDH) as well as the oxidation of the alcohol 47 .…”