Benzyltetrahydroisoquinoline Bases Related to the Alkaloids

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 

Bases with Four Oxygenated Substituents 1. Isolaudanosoline 

Isolaudanosoline is the name given by Franck and Blaschke (196) to the tetraphenolic base CXXXIV (R = H). The tetramethyl derivative (CXXXIV R = CH3) [mp 76°-77° B HCI, 139°-141°] was prepared by Livshits et al. (197) who employed the Bischler-Napieralski reaction although they obtained instead of the usual dihydroisoquinoline base (CXXXV R = H2) the ketone CXXXV (R = O) whose methiodide on reduction afforded CXXXIV (R = CH3). In the absence of oxygen the dihydro base CXXXV (R = H2) can be prepared directly and its methiodide on reduction with sodium borohydride yields CXXXIV (R = CH3) [oil picrate, mp 189°]. When the methiodide of the latter base (CXXXVI R = CH3) was demethylated with hydrobromic acid the methobromide of isolaudanosoline was obtained (CXXXVI R = H). Its oxidation in aqueous solution with ferric chloride afforded an aporphine base (CXXXVII) [chloride, mp 225°-228° bromide, mp 170°-174°] 

The experimental testing of the earlier suggestions that iV-norlaud-anosoline (CXXXVIII R = H) and laudanosoline (CXXXVIII R = CH3) were possible precursors in the biogenesis of alkaloids in plants has provided a stimulus for their further study. 

Labeled bases have been described. When tetrahydropapaverine-l-i C and -3-14C [mp 90° B-HI, mp 256°] were demethylated with hydrochloric acid, the corresponding labeled iV-norlaudanosolines were obtained (113). Resolution of racemic tetrahydropapaverine-3- C by an adaptation of the method of Corrodi and Hardegger (3) afforded the enantiomers (mp 97.5°-98.5° [aju -I-26° 8) (113). Racemic laudano-soline-3-i C has also been prepared (198). 

---