Synthesis of Spirovetivane Sesquiterpenes from Santonin. Synthesis of (+)-Anhydro-beta-rotunol and all diastereomers of 6,11-spirovetivadiene.
The synthesis of the spirovetivane sesquiterpenes (+)-anhydro-beta-rotunol and all the diastereomers of 6,11-spirovetivadiene in enantiomerically pure form has been achieved starting from santonin. The key step is the silicon-guided acid-promoted rearrangement of a 1-trimethylsilyl-4,5-epoxyeudesmane prepared from santonin in several steps involving lactone reductive opening, conjugate addition of TMSLi-CuCN, deoxygenation of a carbonyl group, and epoxidation. Rearrangement of the epoxide gave a spiro[4,5]decanediol which was used as a synthetic intermediate. From this compound, (+)-anhydro-beta-rotunol was prepared after elimination of the primary hydroxyl group in the side chain, followed by allylic oxidation at C8 and elimination of the tertiary hydroxyl group in the cyclohexane ring. On the other hand, elimination of the hydroxyl group in the side chain and reduction of the hydroxyl in the cyclohexane ring gave (-)-premnaspirodiene and (-)-hinesene. The synthesis of the rest of the diastereomers for these compounds required formal inversion of the C5 spiro carbon. The synthesis of these compounds showed that the structure of (-)-agarospirene isolated from Scapania sp. was erroneously assigned, and it has been corrected to be identical to that of (-)-hinesene.
Blay
Gonzalo
G
Departament de Química Orgànica, Facultat de Química, Universitat de València, E-46100-Burjassot (València), Spain.
Cardona
Luz
L
Collado
Ana M
AM
García
Begoña
B
Morcillo
Verónica
V
Pedro
José R
JR
D008968:Molecular Conformation; D012500:Santonin / Q000737:chemistry*; D012717:Sesquiterpenes / Q000138:chemical synthesis*; D013141:Spiro Compounds / Q000138:chemical synthesis*; D013237:Stereoisomerism
D012717:Sesquiterpenes; D013141:Spiro Compounds; C494065:anhydro-beta-rotunol; D012500:Santonin