Total synthesis of spirotryprostatin A, leading to the discovery of some biologically promising analogues

The total synthesis of the title compound has been accomplished. A key step involves the oxidative rearrangement of the beta-carboline derivative to a n oxindole via the action of N-bromosuccinimide. From this point, a diketop iperazine was introduced. A thiophenyl group served as a precursor of the i sopropylidene function. Implementation of the same sort of chemistry starti ng with a methoxytryptophan derivative led to the parent structures. Furthe rmore, it was shown that the difficultly accessible isopropylidene side cha in of spirotryprostatin A is not necessary for biological activity. Moreove r, three analogues lacking the diketopiperazine system were shown to be qui te active as cell cycle inhibitors.