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Model Construction for the A–B–C Ring System of Lysergic Acid via Vilsmeier–Haack ‐Type Cyclization of 1 H ‐Indole‐4‐propanoic Acid Derivatives
Author(s) -
Kurokawa Masayuki,
Watanabe Toshiko,
Ishikawa Tsutomu
Publication year - 2007
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.200790058
Subject(s) - chemistry , propanoic acid , ring (chemistry) , indole test , stereochemistry , substrate (aquarium) , sulfoxide , acetal , intramolecular force , lysergic acid , medicinal chemistry , organic chemistry , oceanography , geology
Vilsmeier–Haack ‐type cyclization of 1 H ‐indole‐4‐propanoic acid derivatives was examined as model construction for the A–B–C ring system of lysergic acid ( 1 ). Smooth cyclization from the 4 position of 1 H ‐indole to the 3 position was achieved by Vilsmeier–Haack reaction in the presence of K 2 CO 3 in MeCN, and the best substrate was found to be the N , N ‐dimethylcarboxamide 9 ( Table 1 ). The modified method can be successfully applied to an α ‐amino acid derivative protected with an N ‐acetyl function, i.e. , to 27 ( Table 2 ); however, loss of optical purity was observed in the cyclization when a chiral substrate ( S )‐ 27 was used ( Scheme 5 ). On the other hand, the intramolecular Pummerer reaction of the corresponding sulfoxide 20 afforded an S‐containing tricyclic system 22 , which was formed by a cyclization to the 5 position ( Scheme 3 ).