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

Abstract

Total Synthesis of (+)-D-Homoestrone 3-methyl ether SummaryA 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 rn-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 A9(")-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 As-isomer 15a add hydrogen from the a-face of the molecule to an extent of about 80%. The 8a-D-homoestrone derivatives 20a and 23 as well as the 9p-isomers 19a and 22 were characterized.

Expeditious Construction of the DEF Ring System of Thiersinine B

“…For the preparation of 5 , we envisaged a stepwise construction of its side chain moiety via α-allylation of 6 to 8 and subsequent chain elongation of 8 to 5 using a cross-metathesis reaction (Scheme ). The allylation of 6 (obtained by treating 7 with PivCl/DMAP/Et 3 N/THF) was attempted, at first, by its conversion into the corresponding dienolate under thermodynamic conditions (NaH/DMSO/THF, NaH/THF/HMPA, KO t -Bu/THF, or KO t -Bu/THF/HMPA) followed by allylation of the dienolate intermediate with allyl bromide. These conditions, however, resulted in the formation of a mixture of the desired monoallylation product 8 , the starting material 6 , and a substantial amount of diallylation product 9 .…”

60 Jahre Steroid‐Chemie in Helvetica Chimica Acta

“…Die Racematspaltung des Endproduktes erfolgte uber die diastereomeren Menthyloxy-acetate.Am Anfang der Bearbeitung der Ostrogene in der Schweiz stand die Partialsynthese von D-Homoostron. Der Kreis schloss sich 1977, als Gutzwiller, Meier und Fiirst iiber eine moderne Totalsynthese von (+)-D-Homoostron-3-methyl-ether (119) ausgehend von dem durch asymmetrische Synthese leicht zuganglichen, (S)-konfigurierten Octalindion 120 berichteten[140]…”