Luzindole

Luzindole (N-0774; N-acetyl-2-benzyltryptamine), is a drug used in scientific research to study the role of melatonin in the body. Luzindole acts as a selective melatonin receptor antagonist, with approximately 11- to 25-fold greater affinity for the MT₂ over the MT₁ receptor. In animal studies, it has been observed to disrupt the circadian rhythm as well as produce antidepressant effects.

Synthesis

Although the "hydrogen bomb" method was reported as 54% yield by Dubococvich, Boehringer Sohn achieved 96% for this step. The difference is that B.I. conducted their hydrogenation under normal pressure at 50°C for 5 hours, whereas Dubocovich conducted theirs at 100 lbs/in2 hydrogen heated to 35°C. This proves that the hydrogenation step proceeds favorably under milder conditions.

The Pictet–Spengler reaction between tryptamine [61-54-1] (1) and benzaldehyde gives 1-Phenyl-tetrahydrocarboline [3790-45-2] (2). Catalytic hydrogenation leads to 2-Benzyltryptamine [22294-23-1] (3). Acylation with acetic anhydride only gave 21% yield of Luzindole (4).

2-iodoaniline [615-43-0] (1) Propargylbenzene [10147-11-2] (2) 2-(3-phenylprop-1-ynyl)aniline, PC85868179 (3) 2-benzylindole [3377-72-8] (4) 1-Dimethylamino-2-nitroethylene [1190-92-7] (5) (6)

One pot Luzindole synthesis:

References