Synthesis of carbohydrates in a continuous flow reactor by immobilized phosphatase and aldolase.

Herein, we report a new flow process with immobilized enzymes to synthesize complex chiral carbohydrate analogues from achiral inexpensive building blocks in a three-step cascade reaction. The first reactor contained immobilized acid phosphatase, which phosphorylated dihydroxyacetone to dihydroxyacetone phosphate using pyrophosphate as the phosphate donor. The second flow reactor contained fructose-1,6-diphosphate aldolase (RAMA, rabbit muscle aldolase) or rhamnulose-1-phosphate aldolase (RhuA from Thermotoga maritima) and acid phosphatase. The immobilized aldolases coupled the formed dihydroxyacetone phosphate to aldehydes, resulting in phosphorylated carbohydrates. A final reactor containing acid phosphatase that dephosphorylated the phosphorylated product yielded the final product. Different aldehydes were used to synthesize carbohydrates on a gram scale. To demonstrate the feasibility of the flow systems, we synthesized 0.6 g of the D-fagomine precursor. By using immobilized aldolase RhuA we were also able to obtain other stereoisomers of the D-fagomine precursor.

Organocatalysed asymmetric Mannich reactions.

The asymmetric Mannich reaction ranks among the most potent enantioselective and diastereoselective C-C-bond forming reactions. In recent years, organocatalysed versions of asymmetric Mannich processes have been increasingly reported and used in a rapidly growing number of applications. This tutorial review provides an overview of the recent history of the asymmetric organocatalysed Mannich reaction, including scope and limitations, and application of different catalyst systems.