Alkaloids spirobenzylisoquinoline

Of five new alkaloids which have been characterized, ledeborine (167 R = Me, r2 = r3 = H, R = OH) is a phenolic alkaloid isolated from Corydalis ledebouriana. The remaining alkaloids, namely raddeanamine (168), rad- 

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The reactions described in this section have been applied to synthesis of a variety of spirobenzylisoquinoline alkaloids (Section V,C,5). 

The spirobenzylisoquinoline alkaloids have been reviewed (1,2,7-10,147) and compiled (148). The exact biosynthetic route to spirobenzylisoquinolines from protoberberine alkaloids has not yet been elucidated (149). 

Biosynthesis of the spirobenzylisoquinoline alkaloid ochotensimine (282) via the quinomethide intermediate (Scheme 49) was proposed by Shamma and Jones (7J0). On the basis of this hypothesis, several biomimetic transformations of phenolic protoberberines to spirobenzylisoquinolines have been realized by the base-induced rearrangement via the quinomethide. 

Almost all types of spirobenzylisoquinoline alkaloids have been synthesized from corresponding protoberberines via 8,14-cycloberbines on the basis of the fundamental reactions described in Section IV,A,1. For example, on irradiation in methanol the phenolbetaine 325 derived from the protoberberine 324 afforded the 8,14-cycloberine 326 in excellent yield (Scheme 60). Sequential... 

Raddeanamine (360) is an unusual spirobenzylisoquinoline alkaloid having a tertiary methyl group in five-membered ring. Methylation of the corresponding ketone gave the methyl carbinol with the reverse stereochemistry, namely, the methyl carbinol 361 was obtained from the reaction of the ketone 294 with methyllithium (Scheme 64). Stereoselective synthesis of ( )-raddeanamine was accomplished by an intramolecular oxyfunctionalization via the 8-methyl-8,14-cycloberbine 364 (175). 

Transformation of phthalideisoquinolines to spirobenzylisoquinoline alkaloids is described in Section V,D,6. 

The spirobenzylisoquinoline 171b derived from berberine (15) (Section IV,A,1) was oxidized with m-chloroperbenzoic acid to the /V-oxide 389, which was treated with trifluoroacetic anhydride to afford dehydrohydrastine (370) in 56% overall yield (Scheme 71) through the Polonovski reaction (187). Holland et al. (188,189) reported the reverse reaction from dehydrophthalides to spirobenzylisoquinolines, namely, 370 was reduced with diisobutylalu-minum hydride to give a mixture of two diastereoisomeric spirobenzylisoquinolines 320 and 348 via the enol aldehyde. This reaction was applied to synthesis of various spirobenzylisoquinoline alkaloids such as (+)-sibiricine (352), ( + )-corydaine (347), (+ )-raddeanone (354), ( )-yenhusomidine (359), (+ )-ochrobirine (343), and ( )-yenhusomine (323). 

Indenobenzazepines have been used as key intermediates for synthesis of rhoeadine, protopine, phthalideisoquinoline, and spirobenzylisoquinoline alkaloids. Several new alkaloids possessing an indenobenzazepine skeleton have been isolated, and they are presumably biosynthesized from proto-berberine alkaloids. 

In the H NMR spectra of spirobenzylisoquinoline alkaloids substituted at C(8) the chemical shift of the 8-proton is diagnostic of its stereochemistry with respect to the nitrogen atom. This is exemplified by the spectra of the diastereoisomeric pair of compounds [108] and [109]... 

Another important route stems from the formation of the N-methylated moieties of the (S)-tetrahydroprotoberberines, which serve as precursors for the protopine, benzophenanthridine, tetrahydrobenzazepines (rhoeadines) and spirobenzylisoquinoline alkaloids (Kutchan and Zenk, 1993 Liscombe and Facchini, 2008 Ziegler and Facchini, 2008) (Fig. 2.7). 

The similar conversion of the spirobenzylisoquinoline alkaloids to inden-oazepine-type alkaloids led to the stereocontrolled syntheses of ( )-rad-deanine (132) and ( )-yenhusomine (133) and the structure revision of... 

A spirobenzylisoquinoline alkaloid, ochrobirine (112) has been synthesized from its biogenetic precursor, coptisine (111) (Scheme 43). The key reaction presented in this biomimetic and stereoselective conversion involves a regioselective C8—N bond fission of the aziridine (113), which is formed from the betaine by photochemical valence tautomerization <79TL3749>. 

Two intriguing models for the biogenesis of spirobenzylisoquinoline alkaloids have been proposed.246,247 Knowledge that aurotensine (265) and other proto-berberine-derived alkaloids co-occur with ochotensine, a spirobenzylisoquinoline... 

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