ABSTRACT
An efficient formal total synthesis of (+) cortistatinsâ A and J has been accomplished, by exploiting a highly diastereoselective intramolecular [4+3] cycloaddition of epoxy enolsilanes as the key reaction to construct ringsâ B and C of the cortistatins in one step.
Subject(s)
Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Isoquinolines/chemical synthesis , Polycyclic Compounds/chemical synthesis , Cycloaddition Reaction , Epoxy Compounds/chemistry , Heterocyclic Compounds, 4 or More Rings/chemistry , Isoquinolines/chemistry , Molecular Structure , Polycyclic Compounds/chemistry , Silanes/chemistry , StereoisomerismABSTRACT
A concise, asymmetric synthesis of the pentacyclic framework of the cortistatins has been accomplished in 12 steps from commercially available starting materials, employing a highly diastereoselective intramolecular (4+3) cycloaddition of epoxy enolsilanes as the key step.
Subject(s)
Heterocyclic Compounds, 4 or More Rings/chemistry , Heterocyclic Compounds, 4 or More Rings/chemical synthesis , Isoquinolines/chemistry , Isoquinolines/chemical synthesis , Polycyclic Compounds/chemistry , Polycyclic Compounds/chemical synthesis , Stereoisomerism , Substrate SpecificityABSTRACT
Using epoxy enol triethylsilanes as oxyallyl cation precursors, [4 + 3] cycloadditions with various dienes occur under catalysis by silyl triflates and acids in good yields. The intramolecular [4 + 3] cycloaddition proceeds under mild conditions and generate hydroxylated cycloadducts with high diastereoselectivity and yields. Enantiomerically pure epoxy enol silanes have been shown to give excellent yields of the optically pure cycloadduct bearing multiple stereocenters.
