Synthetic Studies Concerning the Crinine Alkaloid Haemultine

The racemic form, (+/-)-1, of the structure originally assigned to the crinine alkaloid haemultine has been prepared for the first time. A key step involved the conversion of compound (+/-)-4 into the isomeric cis-C3a-arylhexahydroindole (+/-)-3 using a Pd-0-catalysed intramolecular Alder-ene reaction. The amino-alcohol (+/-)-2 derived from the latter compound reacted with paraformaldehyde in the presence of trifluoroacetic acid to give, via a Pictet-Spengler reaction, the target (+/-)-1. The diastereoisomeric Mosher esters 15 and 16 obtained by coupling the racemate (+/-)-1 with the R-form, 14, of the Mosher acid could be separated chromatographically and then reductively cleaved to give the enantiomerically pure compounds (+)-1 and (+/-)-1, respectively. The physical and spectroscopic data derived from the former enantiomer are consistent with the proposition that the title natural product is, in fact, a mixture of (+)-1 and its Delta(2,3)-double bond isomer.