Model Construction for the A–B–C Ring System of Lysergic Acid via Vilsmeier–Haack-Type Cyclization of 1H-Indole-4-propanoic Acid Derivatives
✍ Scribed by Masayuki Kurokawa; Toshiko Watanabe; Tsutomu Ishikawa
- Publisher
- John Wiley and Sons
- Year
- 2007
- Tongue
- German
- Weight
- 192 KB
- Volume
- 90
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Abstract
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).