Canadine synthesis

RUEFFER, M., ZENK, M.H., Canadine synthase from Thalictrum tuberosum cell cultures catalyzes the formation of the methylenedioxy bridge in berberine synthesis. Phytochemistry, 1994, 36, 1219-1223. 

Cushman and Dekow (SO) performed a synthesis of ( )-canadine (246) by oxidative decarboxylation on LTA treatment (Scheme 28). Thus, LTA oxidation in a mixture of AcOH and dimethylformamide of ( )-cis-2,3-methylenedioxy- 8-oxo- 9,10- dimethoxy-13- carboxytetrahydroprotober-berine (244) in the presence of cupric acetate gave berlambine (245) in 65% yield. Aluminum hydride reduction of 245 afforded ( )-canadine (246) in 63% yield. 

Furthermore, the following compounds were synthetically prepared racemic cheilanthifoline (58c) (47), kikemanine (58d) (129), canadine (58e), berberine (59a) (590, 614), tetrahydropalmatine (58g) (475), sinac-tine (58h), cavidine (68d) (616,617), nandinine (58i) (590, 614, 615), capaurine (58p) (618), capaurimine (58o) (128, 618a), xylopinine (60c) (610, 615, 619), O-methylcaseanadine (62b) (70, 620), thalictricavine (68b), and corydaline (68h) (615). Xylopinine (60c) and some other alkaloids were synthesized by benzoylation of 1-alkyl-3,4-dihydroisoquinolines followed by photocyclization. This method provides a useful route to the synthesis of other protoberberine alkaloids (619). It is also applicable to the synthesis of cularine (51) and spirobenzyltetrahydroisoquinoline alkaloids (188). Xylopinine was also synthesized from the corresponding enamide under benzyne reaction conditions (615). Kametani etal. summarized their findings on the synthesis of these alkaloids and described the formation of protoberberines by debenzylation and photolysis of tetrahydroisoquinolines (622, 623). The total stereospecific synthesis of racemic ophiocarpine (70a) from the 3,4-dihydroisoquinoline derivative by Mannich cyclization was also described (624). 

Scheme 67. Synthesis of optically active ochotensanes from canadine (58e) metho chloride (814).

A synthesis of oxyberberine is also a synthesis of tetrahydroberberine, and the resolution of the latter by means of bromocamphorsulfonic acid (211) to Z-canadine completed the synthesis of this natural base. 

Structure and Synthesis. In addition to the proof of the structure of tetrahydropalmatine by virtue of its preparation from palmatine and the reverse oxidation, the resolution of the dZ-base was accomplished by means of d- and Z-tartaric acids in succession, the d-base d-tartrate and the Z-base Z-tartrate being the forms of least solubility (225). The d- and Z-bases had [a]n +291° (ethanol) and —294° (ethanol), respectively, the natural d-base having [a] +292.5° (58). Spath and Mosettig (226) have also related tetrahydropalmatine directly to tetrahydroberberine, that is to canadine. The d-, Z-, and dZ-forms of canadine were demethylenated by means of phloroglucinol and sulfuric acid yielding the base XXX in its three possible forms, the d-form having +307° (ethanol). These when... 

Pyne has recently extended this methodology to the synthesis of the tetrahydroprotobeberine alkaloid (i )-(H-)-canadine (93) [62]. 

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