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

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 degrees C) and acid promoted intramolecular C - S bond formation leading to a 10- membered cycle are key steps of our synthesis.