Bernard Luke Flynn

The synthesis and tubulin binding activity of thiophene-based analogues of combretastatin A-4

A number of analogues of combretastatin A-4 (1), containing a thiophene ring interposed between the two phenyl groups, have been prepared. The synthesis of these compounds employed a combination of palladium-mediated coupling and iodocyclization techniques. The thiophene compounds 11, 14, 18, and 19 also represent non-benzofused analogues of some recently described tubulin binding benzo[b]thiophenes 3-5. The most active thiophene compounds identified in this study were 11, 14, and 18. Overall they are less active than 1 but exhibit comparable activity to the most active of the benzo[b]thiophenes 3-5. A structure-activity relationship of these compounds is considered.

A multi-component coupling approach to benzo[b]furans and indoles.

A single step access to multiply substituted benzo[b]furans and indoles has been developed.

Three Molecules of an Arylalkyne Reacting with a β-Amino-Substituted α,β-Unsaturated Fischer Carbene Complex to Give Highly Substituted Spiro[4.4]nonatrienes

Abstract A novel mode of reaction towards arylethynes is shown by the β-trimethylsilyl-substituted α,β-unsaturated Fischer carbene complex 10. A mixture of the isomeric, highly substituted spiro[4.4]nonatrienes 12 and 13 (ratios 1.6:1 to 4.5:1) in yields ranging from 34 to 62% is formed by the formal insertion of three alkyne molecules and concomitant or subsequent cyclization. Such selective triple reactions of alkynes with ethenylcarbene complexes have not previously been observed. It is believed that this reaction proceeds via an unprecedented domino sequence of a formal [3+2] cycloaddition, carbene reformation, and formal [2+2+1] cycloaddition process which occur in conjunction with a number of other additional in situ transformations of transient chromium π-complexes.