Towards a total synthesis of the new anticancer agent mensacarcin: synthesis of the carbocyclic core.
A synthesis of the carbocyclic core associated with the new anticancer agent mensacarcin (1) is reported. The strategy involves the synthesis of several novel highly substituted aromatic compounds, such as 12 and 23. The lithium derivative of 12 readily engages in a nucleophilic addition to benzaldehyde 4 to provide the diphenylcarbinol rac-15. The analogous benzyl ether rac-16 undergoes an intramolecular Heck reaction to provide the required tetrahydroanthracene rac-17, which can be transformed into the key tricyclic methyl ether rac-20. In a second approach, the lithium derivative of 21 is added to the hexasubstituted benzaldehyde 23 to give the diphenylcarbinol rac-35. Subsequent methylation to rac-36 followed by an intramolecular Heck reaction provides tricycle rac-37. Similarly, the oxidised compound 40 provides an electronically more suitable intramolecular Heck partner to afford compound 41. Further transformations of these substrates leads to rac-43, which incorporates the core structure of mensacarcin (1).
Tietze
Lutz F
LF
Institut für Organische und Biomolekulare Chemie, Georg-August Universität, Tammannstrasse 2, Göttingen 37077, Germany. ltietze@gwdg.de <ltietze@gwdg.de>
Stewart
Scott G
SG
Polomska
Marta E
ME
Modi
Andrea
A
Zeeck
Axel
A
D000873:Anthracenes / Q000138:chemical synthesis* / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D001969:Bromobenzenes / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D003500:Cyclization; D007462:Iodobenzenes / Q000737:chemistry; D015394:Molecular Structure
D000873:Anthracenes; D000970:Antineoplastic Agents; D001969:Bromobenzenes; D007462:Iodobenzenes; C510239:mensacarcin; D002244:Carbon