CHEMISTRY OF CYCLIC TAUTOMERS OF TRYPTOPHAN - FORMATION OF A QUATERNARY CENTER AT C3A AND TOTAL SYNTHESIS OF THE MARINE ALKALOID (+)-ENT-DEBROMOFLUSTRAMINE-B

A diastereoselective synthesis of the unnatural (+)-enantiomer of the marine alkaloid (-)-debromoflustramine B (1) from a cyclic tautomer (9) of L-tryptophan is described. The optical rotation of the synthetic 1 is opposite to that of the natural material enabling the configuration of the natural product to be established as 3aS,8aR. As natural flustramine B has been converted to (-)-debromoflustramine B its absolute configuration may also be set as 3aS,8aR. The synthetic scheme involves radical bromination of 9 at C3a followed by allylation, at C3a, with allyltributyltin to give 21. The allyl group is then converted to the C3a prenyl derivative 23 by oxidative cleavage and Wittig reaction. The remainder of the synthesis involves removal of the now extraneous carbomethoxy group from C2 and selective removal of the two nitrogen protecting groups and alkylation of the resulting amines. Oxidation of 9 with eerie ammonium nitrate to give mixtures of the C3a nitrato- and hydroxy-derivatives 18 and 19 is also described.