Details

Autor(en) / Beteiligte

• Hsu, Fu-Lian
• Rice, Kenner C.
• Brossi, Arnold

Titel

Total Synthesis of (±)-3-Deoxy-7,8-dihydromorphine, (±)-4-Methoxy-N-methylmorphinan-6-one and 2,4-Dioxygenated (±)-Congeners

Ist Teil von

• Helvetica chimica acta, 1982-07, Vol.65 (5), p.1576-1589

Ort / Verlag

Weinheim: WILEY-VCH Verlag GmbH

Erscheinungsjahr

1982

Quelle

Wiley-Blackwell Journals

Beschreibungen/Notizen

• A total synthesis of racemic 3‐deoxy‐7,8‐dihydromorphine ((±)‐2) and 4‐me‐thoxy‐ALmethylmorphinan‐6‐one ((±)‐3) is described. The key intermediate was 2,4‐dihydroxy‐N‐formylmorphinan‐6‐one (11), obtained from 3,5‐dibenzyloxy‐phenylacetic acid (4) in 41.8% overall yield. Bromination of 11, and treatment with aqueous NaOH‐solution afforded, after N‐deblocking and reductive N‐methylation with concomitant removal of the aromatic bounded Br‐atom, the morphinanone 14. Elimination of the HO–C(2) group in 14 was accomplished by hydrogenolysis of its N‐phenyltetrazolyl ether 15, to give 3‐deoxy‐6,0‐didehydro‐7,8‐dihydromorphine (16). Reduction of 16 with L‐Selectride at low temperature provided (±)‐2 in high yield. The ether 15 directly afforded, under more vigorous reduction conditions, 4‐hydroxy‐N‐methylmorphinan‐6‐one (17). and after O‐methylation of 17, the methyl ether (±)‐3 was obtained. A (1:l)‐mixture of 4‐hydroxy‐2‐methoxy‐N‐methylmor‐phinan‐6‐one (28) and its 2‐hydroxy‐4‐methoxy isomer 30 svere obtained by Grewe‐cyclization of a mono‐methoxylated aromatic precursor similar to that which afforded 11. The 2,4‐dioxygenated N‐methylmorphinan‐6‐ones 29, 31 and 38 were also prepared and characterized.