The highly substituted enantiomerically pure decalinone 2 is the key intermediate of our synthetic approach. It was synthesised using an annulation method developed in our laboratory , starting with cheap, easily available, symmetrical compounds.
Decalinone 2 allows alternative possibilities to close the oxygen bridge and to connect with the further two parts of the macrocyclic lactone. We succeeded in producing an advanced intermediate 3 of Kallmerten's synthesis of 18-desoxynargenicin with the advantage, that in our case 3 is enantiomerically pure.
In a model study we investigated the possibility of coupling the side chain with the decalin part before closing the oxygen bridge. This we achieved by intramolecular reductive coupling of a ketoester.
The protected C-15 to C-19 part of the macrocycle was synthesised via the Evans oxazolidinone technique as the key step.