In the Rawal synthesis (1994, racemic) amine 1 and enone 2 were combined in an amine-carbonyl condensation followed by methyl chloroformate quench to triene 3 which was then reacted in a Diels–Alder reaction (benzene 185 °C) to hexene 4. The three ester groups were hydrolyzed using iodotrimethylsilane forming pentacyclic lactam 5 after a methanol quench in a combination of 7 reaction steps (one of them a Dieckmann condensation). The C segment 6 was added in an amine alkylation and Heck reaction of 7 formed isostrychnine 8 after TBS deprotection.
The overall yield (10%) is to date the largest of any of the published methods