Chiral Economy with Respect to Rotational Isomerism: Rational Synthesis of Hamatine and (Optionally) Ancistrocladine from Joint Helical Precursors

on the occasion of his 70th birthday &&& -Unlike the target alkaloids la and l b , which are configurationally stable at the biaryl linkage, the helicene-like distorted cyclic precursors 2 and 7 show dramatically lowered rotational thresholds: they equilibrate at room temperature, already.In contrast to the lactones 2a/b, however, the cyclic ethers 74 and 7b interconvert slowly enough to be separated conveniently, on a preparative scale.Ring opening of the desired helimer (e.g.7b) and re-equilibrationlre-separation of the rest allows the transformation of practically the whole synthetic material, optionally into lb or lapractising "axially chiral economy".Ancistrocladine3 (la) is the most widespread representative of the naphthylisoquinoline alkaloidsa remarkable group o f meanwhile nearly 30 related, structurally intriguing compounds4.These interesting natural products are found in tropical lianas belonging to the plant families of the Ancistrocladaceae and the Dioncophyllaceae.Biomimetic syntheses of both molecular partsthe naphthalene andthe isoquinoline mietiesfrom identical 0-polycarbonyl precursors strongly suggest an unprecedented biosynthesis from acetate units5.Besides these biosynthetic aspects, the most evident structural feature of la is its highly hindered biaryl linkage, which gives rise to rotational isomers that are configurationally