Synthesis of B/C trans-morphine
1967; Elsevier BV; Volume: 8; Issue: 14 Linguagem: Inglês
10.1016/s0040-4039(00)90684-1
ISSN1873-3581
AutoresHiroshi Kugita, Mikio Takeda, H. INOUE,
Tópico(s)Berberine and alkaloids research
ResumoSYNTHESIS OF B/C TRANS-MORPHINE H. Kugita, M. Takeda and H. Inoue Organic Chemistry Research Laboratory Tanabe Seiyaku Co., Toda, Saitama, Japan (Received 9 January 1967) In a previous paper, we described the synthesis of a B/C trans morphine structure (III) by the hydroboration of A8-dihydrodesoxycodeine? This reaction was extended to some A*-derivatives bearing a substituent on the C-ring in the hope of obtaining various compounds of the B/C trans system for pharmacological v evaluation. This communication concerns with the synthesis of tm-ccdeine and c -morphine. Reaction of isoneopine (prepared in two steps from thebain,e2) and toluenep-sulfonyl chloride in pyridine gave tosylisoneopine (I), C25H27N05S**, m.p. 186-80. Hydroboration of I in tetrahydrofuran and subsequent alkaline oxidation gave trans-6B-tosyloxy-*a-hydroxydihydrodesoxycodeine (II), C25H2qN06S, m.p. 141-20 (benzene), in 74.6% yield with a recovery of I (15%). Reduction of II with lithium aluminum hydride gave the 8a-hydroxy derivative (III), identical with the authentic compound. Boiling of II with potassium acetate in aqueous dimethylformamide gave a mixture which was chromatograghed on alumina to give the trana-6a-acetoxy-8u-hydroxy derivative (IV), C20H25N05, m.p. 161.5-2.5O ( AcOEt-hexane), IR(Nujo1) voH 3200 cm, vco 1740 cm-', trans-6a,8a-dihydroxy derivative (V), C18H23N04, m.p. 144.5-5.5O (AcOEt), IR(Nujo1) ))OH 3380 CIU-~, and a-&-hydroxy-A6-derivative (VI), C18H21N03, m.p. 159-160.50 (AcOEt), IR (Nujol) qOH 3200 cm-l, in 31, 19.4 and 17.4 % yield respectively. Hydrogenation
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