Sodium borohydride → Sodium Hydroxide

Participants

Reaction Steps

N-demethyl-sinomenine may be also be obtained through total synthesis, e.g. by adaptation of the procedures described by Kametani et al., (Kametani, T., et al., Studies on the synthesis of heterocyclic compounds. Part ccc. Synthesis of salutridine, sinoacutine, and thebaine. Formal total syntheses of morphine and sinomenine., J. Chem. Soc. (C), 15:2030-2033 (1969)). Specifically, total synthesis begins with diazotization of (±) 1-(2-amino-3-benzyloxy-4-methoxybenzyl)-1,2,3,4,-tetrahydro-6,7-dimethoxy-2-methylisoquinoline, followed by the thermal decomposition of the resulting diazonium salt. The result would be (±) salutaridine which is converted into (±) thebaine by incubation of (±) salutaridine with methanol and sodium borohydride. After incubation at 0° C. for 1 hour, evaporation of methanol, and extraction with 10% aqueous ammonium chloride and chloroform, the resulting intermediate, a mixture of epimeric alcohols, is treated with N-hydrochloric acid for 1 hour. From this solution (±) thebaine is isolated by liquid-liquid extraction (addition of 10% sodium hydroxide and extraction into chloroform) and a solid liquid purification step using preparative thick-layer chromatography on a silica gel. (±) N-demethyl sinomenine is then synthesized from (±) thebaine using a modification of the procedure of Okabe K., et al., Jap. J. Pharm. Chem. 39:267 (1968). As an alternative to total synthesis, the intermediate products (±) salutaridine or (±) thebaine could be used as starters for N-demethyl-sinomenine synthesis.

Provenance & Evidence