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DOI: 10.1055/sos-SD-215-00081

Ilari, A.; Bonamore, A.; Boffi, A.Science of Synthesis: Biocatalysis in Organic Synthesis, (20152170.

RsSTS-mediated synthesis of novel strictosidine analogues containing the piperazinoindole core instead of the tetrahydro-β-carboline (tryptoline) unit has been reported.[‌31‌] Pyrazino- and piperazino[1,2-a]indole systems deserve a special mention in view of their prominent biological activities linked to advanced pharmaceutical product development.[‌32‌] Current synthetic strategies for this class of compounds, especially for regio- and enantioselective synthesis, require demanding chiral transition-metal catalysts. Thus, the use of enzyme catalysis to gain access to the piperazinoindole scaffold is of high potential interest. 2-(1H-Indol-1-yl)ethanamine (15, IEA) has been synthesized and tested as a possible substrate.[‌31‌] Incubation of recombinant RsSTS wild-type protein with this indole derivative, under neutral conditions in the presence of the monoterpenoid glucoside secologanin (4), results in excellent enzyme-dependent conversion (>95%), as shown by HPLC (Scheme 8). In this transformation, the 3α-(S)-piperazinoindole strictosidine analogue 16 [3α-(S)-PIS] is formed, in which the typical tetrahydro-β-carboline skeleton is replaced by the unusual piperazino[1,2-a]indole framework, representing the first example of a piperazino monoterpenoid indole alkaloid. As is the case for the natural RsSTS substrate tryptamine (6), the complete stereoselectivity of RsSTS delivers exclusively 3α-(S)-PIS (16) by condensation of 4 and 15. The use of the enzyme RsSTS presently provides exclusive access to 16.

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