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Efficient Biomimetic Synthesis of Indole Alkaloids of the Vallesiachotamine Group by a Domino Knoevenagel Hetero Diels‐Alder Hydrogenation Sequence
Author(s) -
Tietze Lutz F.,
Bachmann Jürgen,
Wichmann Jürgen,
Zhou Yifa,
Raschke Thomas
Publication year - 1997
Publication title -
liebigs annalen
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 0947-3440
DOI - 10.1002/jlac.199719970515
Subject(s) - chemistry , knoevenagel condensation , diastereomer , domino , indole test , yield (engineering) , catalysis , organic chemistry , stereochemistry , medicinal chemistry , materials science , metallurgy
An efficient three‐step biomimetic synthesis of the four diastereomeric 18,19‐dihydroantirhines 4a–d starting from the tetrahydrocarboline aldehydes 5a and 5b is described. Domino reaction of the aldehydes 5a and 5b , respectively, with Meldrum's acid ( 6 ) and the enol ethers 8a and 8b in the presence of catalytic amounts of ethylenediammonium diacetate leads to the strictosidine analogues 10a–d and 11a–h , respectively, in 74–86% yield, hydrogenation of which gives mainly 15 and 16 with the skeleton of the vallesiachotamine indole alkaloids (55–86%). In addition, small amounts of 17 and 18 with the corynanthe skeleton are also formed (10–12%). Reduction of both 15 and 16 with LiAlH 4 yields the diastereomeric rac ‐18,19‐dihydroantirhines 4a–d in 78–86% yield.