Total Synthesis of Celastrol, Development of a Platform to Access Celastroid Natural Products.
Celastroid natural products, triterpenes, have been and continue to be investigated in clinical trials. Celastrol, and for that matter any member of the celastroid family, was prepared for the first time through chemical synthesis starting from 2,3-dimethylbutadiene. A triene cyclization precursor generated in 12 steps underwent a nonbiomimetic polyene cyclization mediated by ferric chloride to generate the generic celastroid pentacyclic core. In the cyclization, engagement of a tetrasubstituted olefin formed adjacent all carbon quaternary centers stereospecifically. With access to the carbocyclic core of the family of natural products, wilforic acid and wilforol A were prepared en route to racemic celastrol.
Chemistry Department, The University of Texas at Austin , Norman Hackerman Building, Austin, Texas 78701, United States.
Andrew M
AM
Camelio
Chemistry Department, The University of Texas at Austin , Norman Hackerman Building, Austin, Texas 78701, United States.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , 9500 Gilman Drive MC0657, La Jolla, California 92093, United States.
Trevor C
TC
Johnson
Chemistry Department, The University of Texas at Austin , Norman Hackerman Building, Austin, Texas 78701, United States.|Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego , 9500 Gilman Drive MC0657, La Jolla, California 92093, United States.
Dionicio
D
Siegel
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D053978:Pentacyclic Triterpenes; D014315:Triterpenes / Q000138:chemical synthesis* / Q000737:chemistry
D001688:Biological Products; D053978:Pentacyclic Triterpenes; D014315:Triterpenes; C050414:celastrol