Isoquinoline-type alkaloids

The plants of Hernandiaceae comprise about sixty-five species in four generic kinds. The plants of Hernandia ovigera L. are widespread in the tropics and the subtropics. In Japan, these plants grow on the beaches of Okinawa and Ogasawara islands. In the Okinawa region, the plants have been used as therapeutic agents. A number of groups have been involved in the isolation and structure elucidation of aporphine-type and isoquinoline-type alkaloids from these plant materials as well... 

Opitim contains 10-25% alkaloids, and the main constituent is morphine. Other than morphine, more than 25 alkaloids are known, and among them are other morphinan-type alkaloids (codeine and thebaine), benzyl-isoquinoline-type alkaloids (papaverine and noscapine), and protopine-type alkaloids (protopine). The biosynthetic precursor of all of these alkaloids is phenylalanine. 

About 20 species of plant are known in the genus Ancistrocladus (Ancistro-cladaceae), which grows wild in the tropical areas of Asia, Malaysia, and West Africa. From this genus of plants, as well as two genera of the Dionchophyl-laceae family, naphthalene-isoquinoline-type alkaloids have been isolated. This type of alkaloid is quite rare, and only about 20 such alkaloids have been reported [1]. 

There are no reports on the biosynthesis of this type of alkaloid. It is possible that the origin of these alkaloids is phenylalanine, as for other isoquinoline-type alkaloids. However, because this type of alkaloid possesses a methyl moiety attached to the carbon alpha to the nitrogen atom, like ephedrine and related alkaloids, it is also possible that these alkaloids are derived from a C6-Ci unit, such as benzoic acid or benzaldehyde, as in the case of ephedrine and related alkaloids. That is why these alkaloids are included in this chapter. Elucidation of the biosynthetic pathway for these alkaloids is awaited. 

Miscellaneous Isoquinoline-Type Alkaloids (Type XIII) 330... 

Type XIII—Miscellaneous Isoquinoline-Type Alkaloids... 

Another methods for the electrochemical formation of the active carbanion is the cathodic reduction of iminium salts. When an iminium salt is reduced in the presence of a suitable alkylating agent, an alkyl group is introduced to the carbon atom of the imine. Some isoquinoline and indole type alkaloids are synthesized by using this substitution method as exemplified bellow by the synthesis of laudanosine 51 37>. 

The role of reticuline as an intermediate in the biosynthesis of the mor-phinan alkaloids (Fig. 2.8) was demonstrated by the isolation both of (S)-and (f )-reticuline from the opium poppy. An excess of the (S)-reticuline over the (f )-isomer was found in opium (poppy latex) obtained from the mature plant, in contrast to the roughly equal amounts of these two isomers that occur in poppy seedlings. Both isomers were found to be incorporated into morphine, the major alkaloid isolated from opium, although incorporation of the (f )-isomer was slightly more efficient. (f )-Reticuline is firmly established in P. somniferum as the precursor of the morphinan-type alkaloids (Loefer and Zenk, 1990). (S)-Reticuline, however, is the central intermediate in isoquinoline alkaloid biosynthesis. It has been postulated that (R)-reticuline is formed from (S)-reticuline by isomerization. This inversion of configuration can be explained by the intermediate formation of the 1,2-dehydroreticulinium ion originating from (S)-reticuline, followed by stereospecific reduction to yield the (R) counterpart. The 1,2-dehydroreticulinium ion is efficiently incorporated into opium alkaloids and its role as a precursor of the morphinan-t)q)e alkaloids has been unequivocally established (De-Eknamkul and Zenk, 1990, 1992). 

Numerous reports have also been published on the separation of the individual alkaloids by using ion exchangers (301, 302), various solvents of different pH (303), or multibuffered extraction systems (102, 103, 304-306). The isolation of minor bases from extracts of P. somniferum (254,282, 307-311) and of Fumaria officinalis (166) has been reported. The separation of the bases obtained from this plant material was also carried out by countercurrent distribution (312) and column chromatography (313, 314). The alkaloid coreximine was detected in P. somniferum by an isotope dilution method which was based on the biosynthesis of this alkaloid from reticuline (249). The isoquinoline type of quaternary alkaloids can be... 

Kametani et al. (544,545) and other workers (546-561) endeavored to carry out the synthesis of cularine alkaloids by phenolic oxidation (bio-genetic type of synthesis) of the corresponding derivatives of laudanosine. The paper (549) describes the synthesis of these bases via the 6-ethoxycar-bamido-3,4-dihydroisoquinolines, which were converted to 6-amino-isoquinoline. By Ullmann reaction it gives the compound 52 and ( )-cularine (51) (Scheme 18). Cularine-type alkaloids were also synthesized by the intramolecular Ullmann reaction of 7,8-disubstituted isoquinoline obtained by the usual Bischler-Napieralski reaction from the phenolic bromoamide (pathway a) (544, 548). However, in the papers referred to (557,558,561), the rings A, C, and D were formed first (pathway b), and only then was the ring formed during the synthesis of cularine. 

The large group of alkaloids of the isoquinoline type ranges in complexity from the simple isoquinolines, more exactly defined as simple tetrahydro-isoquinolines, with only one aromatic nucleus, to the complicated structures of the bisbenzylisoquinolines. 

Most of the alkaloids containing an isoquinoline structure that are considered are presented in the following order simple iso quinolines, isoquinolones, and phenethylammonium compounds benzyltetrahydroi-soquinolines bisbenzylisoquinolines and bisbenzyltetrahydroisoquino-lines protoberberines and tetrahydroprotoberberines proaporphines aporphinoids dehydroaporphines 7-substituted aporphines oxoapor-phines phenanthrenes miscellaneous isoquinohne-type alkaloids and nonisoquinoline alkaloids. 

Actually there are no good definitions of alkaloids (Bate-Smith and Swain, 1966) since each one is either too narrow or too broad. Even in the restricted Winterstein and Trier definition, at least five alkaloid families exist that can be derived from different amino acids consequently, there is a need to establish the proper biosynthetic pathways to permit the application of the alkaloid character to chemotaxonomy, It has been mentioned above that canadine (berberidine) may be found in plants of six partially unrelated botanical families. This fact is not surprising when considered in relation to the biochemical investigations of canadine biosynthesis. Many reactions are necessary to convert tyrosine into canadine consequently, one might even wonder why the distribution of this alkaloid is so limited. In contrast, other plants (and even some that produce canadine) can produce many alkaloids that are derived from tyrosine but have a marked difference in structure. Tyrosine serves as the key precursor of alkaloids of the isoquinoline type, but other types of alkaloids, such as colchicine and the Amaryllidaceae and the Erythrina alkaloids, may be synthesized from this amino acid. The nucleus of an alkaloid molecule can arise from different precursors thus the indole nucleus in Erythrina alkaloids arises from tyrosine, while in brucine it comes from tryptophan (Figure 1.5). The alkaloids cinchonamine and cinchonine differ in that cinchonamine has an indole nucleus, while cinchonine (like quinine) has a quinoline nucleus however, they exist in a precursor-product relationship (that is, the quinoline type is derived from the indole type in a one-step reaction). 

The family Annonaceae comprises some 2000 species and only about 150 have been investigated for their chemical constituents. Studies during the past decade have indicated that this family can perform biosynthetic sequences which yield an array of isoquinolines. As examples of the more unique types of isoquinolines, Erythrina alkaloids and the cularines form the subjects of two separate chapters. Relatively little information exists on the pharmacology of the cularines. There are now about 225 bisbenzyl-... 

The reaction is essentially that described by the submitters.8 The procedure illustrates a convenient method for the synthesis of a type of lactone which could serve as an important intermediate in the synthesis of isoquinolones, tetrahydroisoquinolines, and isoquinoline alkaloids Several analogous and closely related lactones have been reported. 

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