Zwitterionic Alkaloids

As shown in Seheme 26, Papaverine hydrochloride yields a separable mixture of Protopapaverine (67) and the salt norpapaverinium chloride (68) when heated slightly beyond its melting point for several minutes. Molecule 67 can exist as conjugated mesomeric betaine 67A (7-hydroxy form) or as 2-substituted-2/7-isoquinolin-6-one 67B (6-hydroxy form) (66TL1177). Similar structures were described as zwitterionic pentacyclic 

10-Methoxy-3,4,5,6-tetradehydrocorynantheol (286), 3,4,5,6,18,19-Hexade-hydroochropposinine (287), 3,4,5,6-Tetradehydrositsirikine (288), Alstonine (289), the no-name-alkaloid (290) (Mitragyna speciosa) (98T8433), 3,4,5,6-Tetradehydropalicoside (291) and its methylester which were isolated recently from Strychnos mellodora (99P1171), Serpentine (292), and Serpentinine (293) are known representatives of this class of alkaloids. 

Total syntheses of racemic Melinonine E (316) and Strychnoxanthine (317) were performed using a radical cyclization process as the key step (98JOC968). Melinonine E was first isolated from the bark of Strychnos melinoniana in 1957 (57HCA1167), but structure elucidation was not carried 

The key step of an interesting synthesis of Sempervirine (327) is a triazine Diels-Alder annulation reaction with an enamine (88T3195). 1- 

334 was then accomplished in 45% yield for the two steps. Sodium amalgam under carefully controlled conditions caused a complete desulfonylation without reduction of the pyridine ring. Treatment of the sulfonylated species 

335 with butyl lithium followed by quenching with bromoacetaldehyde provided the indoloquinolizinium bromide 336, which on alkaline hydrolysis yielded the zwitterionic Sempervirine (327). 

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Two new zwitterionic alkaloids with a 5,6-dihydroindolo[2,3-a]quinolizine ring system have been isolated from Vinca major L. var. elegantissima Hort (13). The structures of vincarpine (4) and dihydrovincarpine (5) have been determined on the basis of their spectral data and via some derivatives obtained by either catalytic or hydride reduction. Interestingly, the H-NMR spectrum of vincarpine in TFA solution corresponds to structure 6 derived by lactonization of 4 in the presence of acid. 

In 1966, Hirata et al. isolated yuzurimine (12) as one of the major alkaloids from D. macropodum and reported the crystal structure of yuzurimine hydrobromide [25]. They also isolated the two related alkaloids yuzurimines A (13) and B (14), whose structures were elucidated through spectroscopic data and chemical evidence in 1972. At almost the same time, Nakano et al. isolated macrodaphniphyllamine (16), macrodaphniphyllidine (17), and macrodaphnine (18) [15,29], whose structures were identical with deacetyl yuzurimine A, acetyl yuzurimine B, and dihydroyuzurimine, respectively. Yamamura et al. isolated deoxyyuzurimine (19) from D. humile [30], and daphnijsmine (20) and deacetyl daphnijsmine (21) from the seeds of D. teijsmanni [23]. Calycinine A (22) was isolated from D. calycinum distributed in China, together with deacetyl daphnijsmine, deacetyl yuzurimine, and the zwitterionic alkaloid 26 [31] (Figure 18.3). 

Daphnilactone B (24) was isolated as one of the major alkaloids from the fruits of three Daphniphyllum species in Japan, D. macropodum, D. teijsmanni, and D. humile, and the structure was deduced by extensive spectral analysis, as well as by chemical evidence, and finally assigned by X-ray crystallographic analysis [34,35,37]. Isodaphnilactone B (25) was isolated from the leaves of D. humile and the structure was analyzed by spectroscopic methods [30]. A zwitterionic alkaloid 26, the hydration product of daphnilactone B, was isolated from the fruits of D. teijsmanni, and the structure determined on the basis of its spectral and chemical properties [38]. 

Daphnine (191), the highly conjugated N(2) zwitterionic alkaloid from Daphnandra dielsii and D. repandula (Monimiaceae), is the sole representative of this type of alkaloid. Daphnine is of very restricted distribution to the genus Daphnandra. 

The medicinal Indian plant Abrus precatorius elaborates the ester precaterine (99), and a number of simple pyridine Zwitterionic alkaloids of established structure, such as trigonelline (lOO) (S. Ghosal and S.K. Dutta, Phytochem., 1971, 10, 195). 

Two further quaternary pyrrolizidine alkaloids have been isolated by Sasaki and Hirata from Anodendron affine Druce. These are anodendrine (26) and its C-1 epimer alloanodendrine. In confirmation of these structures, anodendrine gave (+ )-laburninic acid (27) on palladium-catalysed hydrogenolysis, whereas alloanodendrine gave (-t-)-isoretronecanolic acid, the C-1 epimer of (27). The structures of both zwitterionic alkaloids were then finally established by synthesis. 

Anodendrine (17) and alloanodendrine (18) are a pair of zwitterionic alkaloids whose structure was determined by a combination of physical and chemical methods. The synthesis of the former was achieved by treating the methyl ester of labrnninic acid with isopentenyl bromide and hydrolysing the product. The alio base was similarly prepared from (+ )-isoretronecanolic acid (12). 

Daphilactone-B (4) is a major component of several alkaloids isolated from the fruits of three kinds of plants growing in Japan (7). Further examination of the alkaloidal components in the fruits of the species Daphniphyllum teijsmanni Zollinger (70) led to the isolation of a zwitterionic alkaloid (32) (Fig. 4), which was recently proved to be only one major component of the water-soluble fraction of the methanol extract (76). This alkaloid [32 mp 247-248°C C22H33O3N miz 359 (M+)] produces the following spectral data (Nujol)... 

H, br s, Wh 5 Hz). From these spectral data, indicating the presence of a hydroxymethyl group (83.70 and 4.29) and a carboxylate 1595 and 1575sh cm ). this zwitterionic alkaloid is regarded as the hydration product of daphnilactone-B (4). In fact, 32 was readily converted to a mixture of daphnilac-tone-B (4) and a methyl ester (33) on treatment with anhydrous MeOH containing HCl gas (room temp., 5 hr) followed by NaHCOj. 

Sasaki, K., and Y. Hirata The Structures of Two New Zwitterionic Alkaloids from... 

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