Intramolecular Pictet-Spengler reaction of N b-Alkoxytryptamines. 4. A study towards diastereocontrol in the synthesis of tetracyclic eudistomins

Abstract

The diastereoselectivity of the intramolecular Pictet-Spengler condensation in the synthesis of tetracyclic eudistomins is described. N b-Alkoxytryptamines 15a–m were synthesized with different sized groups R 2. Closure of the 7-membered oxathiazepine ring was accomplished in 66–98% yield. With the intramolecular approach diastereoselectivity can be achieved for the unnatural trans isomer. An indole methylated derivative was also synthesized giving the interesting cis/trans pentacyclic spiro compounds 19 and 20. These results are interpreted in terms of a kinetically favoured electrophilic attack at the indole-3 position, whereas β-carboline formation is the result of a slower route via electrophilic attack at the indole-2 position.