A highly convergent synthesis of the methyl ether derivative 2a of the naphthylisoquinoline alkaloid ancistrocline (2) is described. The key step involves a stereoselective biaryl coupling between the chiral oxazoline 3 and the Grignard reagent 4 derived from the optically active tetrahydroisoquinoline 8. The atropisomeric mixture was then converted to the separable acetamides 11 and 12, which were obtained in a ratio of 16:84 and an overall yield of 32% for the three steps. The major atropisomer 12 was then converted into O-methylancistrocline (2a), which was identical to a semisynthetic sample derived from the related alkaloid ancistrocladinine (14).

The asymmetric syntheses of (+)-rottnestol (1) and the related marine sponge metabolites (+)-raspailols A (5) and B (6) are described. The key step in each of these sequences was a Stille coupling to form the C9-C10 sp2-sp2 bond and connect the polyene sidechains to the appropriate optically active tetrahydropyran core. For rottnestol (1), both C12 epimers were synthesised by a coupling between stannane 7 and (R)- or (S)-8 followed by acid hydrolysis which allowed for the assignment of the absolute configuration at the remote C12 stereocentre as R upon comparison of chiroptical data of the synthetic material with that reported for the natural product. In accord with this, (12R)-raspailol A (5) was synthesised from stannane 7 and sidechain 9 and this compound also compared well with the data for natural material including sign and absolute value of the specific rotation. Finally, the same C12 epimer of raspailol B (6) was secured via a union between stannane 10 and iodide 9 and this also possessed a similar rotation to that described for the natural product. Thus, all three compounds appear to possess the (12R) configuration, while that of the core tetrahydropyran ring is the same as proposed originally.

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