Total synthesis of FR901464, an antitumor agent that regulates the transcription of oncogenes and tumor suppressor genes.
FR901464 is a potent anticancer agent that regulates the transcription of oncogenes and tumor suppressor genes. A convergent enantioselective synthesis of FR901464 was accomplished in 13 linear steps. Central to the synthetic approach was the diene-ene cross olefin metathesis reaction to generate the C6-C7 olefin, without the use of protecting groups, as the final coupling. Additional key reactions include a Zr/Ag-promoted alkynylation to set the C4 stereocenter, a mild and chemoselective Red-Al reduction, a stereoselective Mislow-Evans-type [2,3]-sigmatropic rearrangement to install the C5 stereocenter, a Carreira asymmetric alkynylation to generate the C4' stereocenter, and a highly efficient ring-closing metathesis-allylic oxidation sequence to form an unsaturated lactone.
Albert
Brian J
BJ
Department of Chemistry, University of Pittsburgh, 219 Parkman Avenue, Pittsburgh, PA 15260, USA.
Sivaramakrishnan
Ananthapadmanabhan
A
Naka
Tadaatsu
T
Koide
Kazunori
K
D000480:Alkynes / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D011714:Pyrans / Q000138:chemical synthesis; D012834:Silver / Q000737:chemistry; D013141:Spiro Compounds / Q000138:chemical synthesis; D013912:Threonine / Q000031:analogs & derivatives / Q000138:chemical synthesis; D015040:Zirconium / Q000737:chemistry
D000480:Alkynes; D000970:Antineoplastic Agents; C104486:FR 901464; D011714:Pyrans; D013141:Spiro Compounds; D013912:Threonine; D012834:Silver; D015040:Zirconium