Model Construction for the A–B–C Ring System of Lysergic Acid via Vilsmeier–Haack‐Type Cyclization of 1H‐Indole‐4‐propanoic Acid Derivatives |
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Authors: | Masayuki Kurokawa Toshiko Watanabe Tsutomu Ishikawa |
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Institution: | 1. Graduate School of Pharmaceutical Sciences, Chiba University, 1‐33 Yayoi, Inage, Chiba 263‐8522, Japan, (phone: +81‐43‐290‐2910;2. fax: +81‐43‐290‐2910) |
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Abstract: | Vilsmeier–Haack‐type cyclization of 1H‐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 1H‐indole to the 3 position was achieved by Vilsmeier–Haack reaction in the presence of K2CO3 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). |
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Keywords: | Lysergic acid 1H‐Indole‐4‐carboxamide 1H‐Indole‐4‐propanoic acid derivatives Vilsmeier– Haack reaction Cyclization reactions Pummerer reaction |
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