Premium
Total Syntheses of (−)‐Strictosidine and Related Indole Alkaloid Glycosides
Author(s) -
Sakamoto Jukiya,
Umeda Yuhei,
Rakumitsu Kenta,
Sumimoto Michinori,
Ishikawa Hayato
Publication year - 2020
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202005748
Subject(s) - indole test , chemistry , enantioselective synthesis , stereochemistry , biocatalysis , biosynthesis , total synthesis , indole alkaloid , chemical synthesis , biomimetic synthesis , combinatorial chemistry , organic chemistry , reaction mechanism , enzyme , biochemistry , catalysis , in vitro
A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α‐cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (−)‐strictosidine, which is an important intermediate in biosynthesis. This two‐step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (−)‐strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (−)‐strictosamide, (−)‐neonaucleoside A, (−)‐cymoside, and (−)‐3α‐dihydrocadambine.