Total synthesis of spirotryprostatin A, leading to the discovery of some biologically promising analogues Academic Article uri icon

Overview

MeSH Major

  • Antineoplastic Combined Chemotherapy Protocols
  • HSP90 Heat-Shock Proteins
  • Neoplasms
  • Proto-Oncogene Proteins

abstract

  • The total synthesis of the title compound has been accomplished. A key step involves the oxidative rearrangement of the β-carboline derivative to an oxindole via the action of N-bromosuccinimide. From this point, a diketopiperazine was introduced. A thiophenyl group served as a precursor of the isopropylidene function. Implementation of the same sort of chemistry starting with a methoxytryptophan derivative led to the parent structures. Furthermore, it was shown that the difficultly accessible isopropylidene side chain of spirotryprostatin A is not necessary for biological activity. Moreover, three analogues lacking the diketopiperazine system were shown to be quite active as cell cycle inhibitors.

publication date

  • March 17, 1999

Research

keywords

  • Academic Article

Identity

Digital Object Identifier (DOI)

  • 10.1021/ja983788i

Additional Document Info

start page

  • 2147

end page

  • 2155

volume

  • 121

number

  • 10