Application of a double Mannich reaction using bis(aminol) ethers in the synthesis of AE ring analogues of methyl lycaconitine
An efficient method for the construction of azabicyclo[3.3.1]nonanes and azabicyclo[3.2.1]octanes is reported via double Mannich reaction of cyclic ketoesters with bis(aminol) ethers. This method is applied to the synthesis of AE ring analogues of methyl lycaconitine.
Brocke, Constanze,Brimble, Margaret A.,Lin, Diana S.-H.,McLeod, Malcolm D.
Efficient synthesis of the azabicyclo[3.3.1]nonane ring system in the alkaloid methyllycaconitine using bis(alkoxymethyl)alkylamines as aminoalkylating agents in a double Mannich reaction
The double Mannich reaction of cyclic β-keto esters with bis-(alkoxymethyl)alkylamines provides an efficient and versatile method for the construction of azabicyclo[3.3.1]nonanes and azabicyclo[3.2.1]octanes. The optimum conditions for efficient reaction involve use of the activator trichloromethylsilane in acetonitrile as solvent at ambient temperature. The utility of this synthetic method is further demonstrated by the facile synthesis of several AE ring analogues 39, 42 of the alkaloid methyllycaconitine by appendage of the key N-(methylsuccininimido)anthranilate pharmacophore to the N-(3-phenylpropyl)-substituted double Mannich adducts 18, 27. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005.
Brimble, Margaret A.,Brocke, Constanze
p. 2385 - 2396
(2007/10/03)
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