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A Bioinspired Synthesis of (±)‐Rubrobramide, (±)‐Flavipucine, and (±)‐Isoflavipucine
Author(s) -
Mizutani Shoma,
Komori Kenta,
Taniguchi Tohru,
Monde Kenji,
Kuramochi Kouji,
Tsubaki Kazunori
Publication year - 2016
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.201602910
Subject(s) - glyoxal , chemistry , regioselectivity , ring (chemistry) , isomerization , circular dichroism , cascade reaction , stereochemistry , combinatorial chemistry , organic chemistry , catalysis
A biomimetic synthesis of naturally occurring lactams rubrobramide, flavipucine, and isoflavipucine is described. The key step is a regioselective Darzens reaction between isobutyl glyoxal and an α‐bromo‐β‐ketoamide. The construction of the core tricyclic ring system of rubrobramide was achieved by a cascade reaction in a single step from an α,β‐epoxy‐γ‐lactam. Furthermore, the absolute configuration of naturally occurring (+)‐rubrobramide was determined by vibrational circular dichroism. (±)‐Flavipucine and (±)‐isoflavipucine were synthesized from an epoxyimide, which was prepared by reaction of isobutyl glyoxal with a protected α‐bromo‐β‐ketoamide. Deprotection of the epoxyimide and formation of the pyridone ring gave (±)‐flavipucine, which was converted into (±)‐isoflavipucine by thermal isomerization.