Total synthesis of tetrahydroisoquinoline and and#946;carboline alkaloids using ellmans chiral auxiliary

Abstract

In 1950s, the ipecac alkaloids such as emetine, dihydrotetrabenazine (1, DTBZ), and tetrabenazine (2, TBZ) were first isolated as racemic mixtures (Fig. 1). Of these, dihydrotetrabenazine is an active metabolite of tetrabenazine. The racemic tetrabenazine has recently been approved as a drug candidate by FDA for the treatment of Chorea, which represents a major advancement of Huntington s disease (HD). The clinical research test reveals that TBZ dramatically decreases the Chorea when compared to the patients treated with placebo. TBZ and DTBZ are useful as vesicular monoamine transporter 2 (VMAT2) inhibitors. The radio labeled TBZ and DTBZ are used as radiotracers in Positron Emission Tomography (PET) for imaging the dopamine neuron degeneration diseases and recently the beta-cell mass related to diabetes. Due to its promising biological activity, DTBZ has attracted many synthetic chemists to take up its total synthesis. As a result, various approaches have appeared in the literature. newline