Studies on structures and syntheses of arteannuin and its related compounds: XVII. The stereocontrolled total synthesis of methyl dihydroarteannuate-The total synthesis of arteannuin

Abstract

This paper reports the total synthesis of 11 R(-)-methyldihydroarteannuate (3) starting from 10 R (+)-citronellal (4). Compound 3 has already been used as starting material for the synthesis of arteannuin (1) through the photooxygenation of the key intermediate compound 2 by us. Thus, the total synthesis of arteannuin from 4 was accomplished. 10R(+)-citronellal (4) was submitted to cyclization and hydroboration to afford dihydroxy compound 5. After selective benzylation of the primary hydroxyl group, oxidation gave the ketone 6. Kinetic deprotonation of 6 and treatment of the resulting enolate with 3-trimethylsilyl-3-buten-2-one provided 1, 5-diketone 7. Cyclization of 7 with Ba(OH)_2·8H_2O and dehydration of the cyclization product with oxalic acid gave α, β-unsaturated ketone 8. 8 was reduced with sodium borohydride, and the reduction product was oxidized to the ketone 9. Both compounds 8 and 9 all showed a positive CE in its CD, therefore the α-orientations of 1-H in 8 and 6-H in 9 could be assigned respectively. When 9 was reacted with methyl Grignard reagent followed by dehydration with p-TsOH, a mixture of 10 and its △~3-isomer was obtained in 1:1 ratio, and pure 10 was isolated from the mixture by flash chromatography. Debenzylation followed by oxidation of the resulting alcohol gave 11. Compound 11 was esterified with CH_2N_2 to give the target compound 3 which is identical in all spectroscopic characteristics with those of 3 obtained from reduction of methyl arteannuate.