Synthetic studies on ecteinascidin 743: rapid access to the fully functionalized tetrahydroisoquinoline with a bridged 10-membered sulfur containing macrocycle

Abstract

Synthesis of tetrahydroisoquinoline with a 1,4-bridged 10-membered sulfur containing macrolactone (5) is described. Phenolic aldolisation, Pictet–Spengler cyclisation of an acid sensitive amino diol under newly developed conditions (LiBr, toluene–TFE, 80 °C) and acid promoted intramolecular C–S bond formation leading to a 10-membered cycle are key steps of our synthesis.