An efficient and selective access to 1-substituted and 3-substituted derivatives of luotonin A

A method for the selective introduction of a substituent into position 1 or position 3 of the antitumour alkaloid, luotonin A, is described. The protocol involves a base-catalysed intramolecular [4+2] cycloaddition reaction of an arylpropargyl unit with a carbonitrile as the key step. These educts are conveniently accessible in two steps from a known precursor. The newly developed route is orthogonal to a previously used cycloaddition approach, which gave access to 2- or 4-substituted luotonin A derivatives.