Conformational energetics of cationic backbone rearrangements in triterpenoid biosynthesis provide an insight into enzymatic control of product.
2,3-( S)-Oxidosqualene (C 30H 50O) serves as a versatile starting point for the remarkable biosynthesis of many isomeric naturally occurring triterpenoids of formula C 30H 50O. These biosyntheses all involve polycyclization via cationic intermediates. The fully cyclized primary products then are converted to various structures by cationic rearrangements involving the polycyclic backbone. The energetics of these rearrangements has been examined by B3LYP 6-31 G* DFT calculations and by ab initio Hartree-Fock calculations at the 6-31G* or 3-21G(*) level. The results have led to the conclusion that the biosynthesis of friedelin, the most drastically rearranged of the pentacyclic triterpenes, involves a complex nonstop process, with no stable intermediates between 2,3-( S)-oxidosqualene and friedelin. It is proposed that this single-reaction biosynthesis consists of pentacyclization to the lupanyl cation followed directly by a sequence of 10 suprafacial 1,2-shifts of carbon and hydrogen, driven by the large exergonicity of the pentacyclization and electrostatic acceleration of the rearrangement steps.
Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02138, USA.
László
L
Kürti
Rong-Jie
RJ
Chein
E J
EJ
Corey
D002412:Cations; D008956:Models, Chemical; D008968:Molecular Conformation; D013185:Squalene / Q000031:analogs & derivatives / Q000737:chemistry / Q000378:metabolism; D013816:Thermodynamics; D014315:Triterpenes / Q000737:chemistry* / Q000378:metabolism*; D000094042:Lupanes
D002412:Cations; D013185:Squalene; D014315:Triterpenes; C002821:2,3-oxidosqualene; C060796:friedelin; D000094042:Lupanes