Applications protoberberine

A third conversion was achieved by application of photochemical transformation of a spirobenzylisoquinoline to a protoberberine (243,244). Hydro-genolysis of the urethane 149 followed by hydrolysis gave the amino ketone... 

Several applications of this methodology have appeared from Mariano s group, however, we will demonstrate the synthetic potential of this discovery by citing here the two most important examples. Synthesis of ( +) Xylopinine (205), a protoberberine alkaloid, has been performed [161] from the photocyclisation of 204 in methanol. Similarly, a erythrane ring system (207) has been constructed [162] from the photoreactions of 206. Some other interesting aspects of this chemistry have been related to a novel Pictet-Spengler [163] type cyclisation and the chemistry of allene cation radicals [164]. 

The phenanthridine skeleton is synthesized by photocyclization of the enamides prepared from cyclohexanonimines and benzoyl chlorides (17,18). The benzo[c]phenanthridine skeletons are formed from the enamides prepared from 2-tetralonimines and benzoyl chlorides (19,20). More conveniently, the skeletons of protoberberine alkaloids are readily synthesized from the enamides prepared by simple acylation of 1 -methyl-3,4-dihy-droisoquinolines with benzoyl chlorides (21-24). This berbine synthesis is one of the most typical examples of the application of enamide photocyclization to alkaloid synthesis and can be further extended to the facile synthesis of the skeletons of the yohimbine group of indole alkaloids (25,26). 

Preformed cyclic /V,A-dialkyliminium salts i.e. where a ring Joins the a-caibon and positively charged nitrogen) have been used in enolate condensation reactions. The number of examples, however, is rather limited, probably because of complications arising through abstraction of enolizable protons. A -Dehy-droindolizidinium salt (69) represents one of the few examples of an enolizable, cyclic A, -dialkylimi-nium salt known to react with an enolate (equation 8). The use of a soft zinc enolate in this reaction may be crucial. The relative stereochemistry of the resulting 3-amino ester (70) is undefined. /V-Alkyl-3,4-dihydroisoquinolinium salts e.g. 71), a class of nonenolizable, cyclic iminium salts, have had extensive applications in the total synthesis of protoberberine and phthalide isoquinoline alkaloids. A review by Pai and coworkers has covered much of this work. In a more recent application by Yamazaki and co-... 

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). 

Mori and Ban reported the novel syntheses of benzolactams and lactones from o-haloarylalkylamines and -alcohols using Pd(OAc)2 and PPh3 in the presence of BU3N under carbon monoxide. As an application of this methodology, they succeeded iu the total synthesis of sendaverine (7, Scheme 3) by very short steps. °i The key step is the formation of isoquinolone 6a by Pd-catalyzed carbonylation of aryl bromide 5a. Pandey later reported the synthesis of benzyl-tetrahydroisoquinolines using a similar proce-dure.f This procedure was also used for the total synthesis of protoberberine alkaloids. ... 

Cyclotrimerization of alkynes into the benzene ring has found numerous applications in the syntheses of natural compounds such as protoberberine skeleton [84], precursors of aromatic steroids [85], and tetracyclic terpenes [86]. A typical example is the short synthesis of estrone 147, in which the whole steroid framework 149 was assembled from the starting diyne 148 in one step (Scheme 65) [87]. 

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