Totalsynthese von (+)-D-Homoöstron-3-methyläther

Total Synthesis of (+)-D-Homoestrone 3-methyl ether A novel total synthesis of (+)-D-homoestrone 3-methyl ether (21) is described starting from (S)-8a-methyl-3,4,8,8a-tetrahydro-2H, 7H-naphthalene-1,6-dione (1) as a chiral synthon for the rings C and D. The key step involves alkylation of the derived 3 with m-methoxyphenacyl bromide (4) as an AB-building block to give the dioxo-secosteroid 5. Hydrogenation of 5 affords the trans-decalone 11. As by-products the epimeric cis-decalones 12 and 13 were characterized. Cyclization of 11 leads under kinetic control predominantly to the Δ9(11)-tetraene 14. Catalytic hydrogenation of 14 and subsequent modification in ring D give the title compound 21. It was found that 14 and also the derived Δ8-isomer 15a add hydrogen from the α-face of the molecule to an extent of about 80%. The 8α-D-homoestrone derivatives 20a and 23 as well as the 9β-isomers 19a and 22 were characterized.