Benzyltetrahydroisoquinoline precursor

Martin RO, Warren ME Jr, Rapoport H (1967) The biosynthesis of opium alkaloids. Reticuline as the benzyltetrahydroisoquinoline precursor of thebaine in biosynthesis with carbon-14 dioxide. Biochemistry 6 2355-2363... 

An interesting variation on the above theme for the biosynthesis of the pavines and isopavines has been proposed by Dyke (169). This proceeds via a quinone methine intermediate. The precursor, a l-benzyltetrahydroisoquinoline-3-car-boxylic acid 165 oxidizes to a quinone methide 166, which then decarboxylates to afford a reactive enamine 167. Cyclization then readily furnishes a pavine. Alternatively, hydration of the enamine 167 at C-4 would ultimately result in formation of an isopavine (Scheme 36). 

Simple isoquinolines are not found in the Menispermaceae of South America. The isoquinolone thalifoline (1) was identified from Abuta pahni [32], Benzyltetrahydroisoquinolines are the biogenetic precursors for aporphines, proaporphines, and oxoaporphines. Yet the only such compound isolated from South American Menispermaceae is (+) coclaurine (2) obtained from Sciadotema eichleriam [52] and Caryomene olivascens [37-38]. The chemistry of simple isoquinolines [65], isoquinolones [66], and benzyltetrahydroisoquinolines [67] have been reviewed. 

By resolution of the benzyltetrahydroisoquinoline or preferably asymmetric reduction with a chiral borohydride of the precursor the chiral members of the series should be accessible bearing in mind the the efficient transformations already acomplished (ref. 167). In the light of potential shortages (ref. 186) and avoidance of dependence upon the sole natural commercial sourse, this synthetic strategy represents a practical approach to the medical opiates. 

The new interest in synthetic 1-benzyltetrahydroisoquinoline bases related to the natural alkaloids arises from the possibility of using them as precursors in biogenetic experiments and as model compounds in the... 

The first proaporphine described in the literature was pronuciferine isolated from Nelumbo nucifera (Nymphaceae) and its chemical was structure elucidated by Bemauer in 1963 30). This alkaloid was isolated again in 1968 from Stephmia glabra 31). At that time it was the only known precursor to the aporphines. However, it is known today that the aporphines can also be formed directly from benzyltetrahydroisoquinolines. 

---