Enantiospecific synthesis of (R)-4-amino-5-oxo-1,3,4,5-tetrahydrobenz[cd]indole, an advanced intermediate containing the tricyclic core of the ergots

We report a new strategy for the enantiospecific synthesis of (R)-4-amino-5-oxo-1,3,4,5-tetrahydrobenz[cd]indole. This compound is an advanced intermediate which contains the tricyclic core of many of the tetracyclic ergot alkaloids. Our method involves the initial synthesis of D-4-bromotryptophan from the coupling of an indolyllithium species with a masked serinal. The alpha-amino position was protected with an N-trityl group, ensuring the enantiomeric integrity of this position during the ensuing organometallic cyclization reaction. Stabilization of the tricycle was accomplished by protecting the indole nitrogen with a BOC group or by reducing the alpha-amino ketone to the corresponding beta-amino alcohol.