Alkaloids isoquinoline family

Biosynthetic research relating to the isoquinoline family was extremely successful, with such important members as morphine [3, 14], codeine [3, 15] or berberine [3, 14,16-18]. Extensive efforts have provided details pertaining to multiple sets of enzymes participating in the biosynthesis of the alkaloids above, in many cases with the help of plant cell suspension culture techniques. Since 1988, when the breakthrough in cloning of cDNA from alkaloid biosynthesis occurred [19, 20], a significant number of enzymes known from the indoles and isoquinolines biosynthesis have been isolated, their biochemical properties described and the majority of their corresponding cDNAs cloned and functionally over-expressed in non-plant hosts such as Escherichia coli, yeast or insect cells. 

Since the late 1950s PMR spectroscopy has contributed immensely to many areas of the chemistry of alkaloids (7). With the advent of Fourier transform spectrometers CMR has rapidly approached the level of PMR in its application to problems of structural elucidation and stereochemistry. In the case of the alkaloids many classes of the isoquinoline family have been studied. These alkaloids are of particular interest not only because of their widespread occurrence in nature but also because of their pharmacological activity (2-5). Wenkert et al. (6) were the first to review progress in this area. More recently, Shamma and Hindenlang (7) have made an extensive compilation of chemical shift data on amines and alkaloids that includes many... 

The protopine alkaloids have a 10-membered ring containing a carbonyl group and a tertiary nitrogen atom. Even though they do not have an isoquinoline ring they are properly classified in the isoquinoline family... 

These alkaloids are a relatively small group within the isoquinoline family. Ochotensimine (101) was the first to be studied and it and ochotensine are the only compounds of the group that have an exocyclic methylene on the five-membered ring (2, 3, 62). The most common functional groups are carbonyl, hydroxyl, or acetoxy at one or both of C-8 and C-13. The spectra of a series of these alkaloids were reported in 1977 (63) and these data were used recently in the structural elucidation of a new alkaloid (64). The structures and spectral data on the alkaloids discussed in this section may be found in Fig. 19 and Table XVIII, respectively. They are ochotensimine (101), sibiricine (102), corydaine (103), ochrobirine (104), fumaritine (105), and fumaritine A-oxide (106). 

Besides his classic studies on the isoquinoline family of alkaloids, Manske also undertook, in collaboration with Leo Marion, an examination of the Lycopodiaceae native to Canada. From this work some thirty alkaloids were characterized, and though he did not himself participate in a major way in their structural elucidation, he always followed the work with interest and insight. Other alkaloids with which he was concerned were members of the Senecio and Lobelia families, and in the latter group he discovered lobinal-ine, the first dimeric member of this family to be isolated. 

Many stmctures are found in the isoquinoline family of alkaloids (see section 3.2), and the Bischler-Napieralski method has been of considerable value in synthesizing some of them. An example is the synthesis of papaverine, 4.20 (Scheme 4.18, where Ar refers to the dimethoxyphenyl substituent). 

B/sbenzylisoquinolins alkaloids isoquinoline alkaloids containing 2 fused benzylisoquinoline nuclei joined by one, two or three diaryl ether linkages. The ether linkages arise by phenol oxidation. B. a. occur in plants of the Menispermaceae and related families, which include the genera Berberis, Magnolia, Daph-nandra and Strychnos. 

Phenylethylamines and simple isoquinolines are found scattered among ca. 40 families and in over half of these one or other or both types of compound are not accompanied by any more complex alkaloids. The families in which they occur are distributed throu out the plant kingdom. They are especially common in the Cactaceae and Chenopodiaceae (Caryophyllales), Fabaceae (Fabales), and Rutaceae (Rutales), families that belong to orders fairly close to those in which the more complex isoquinoline bases are mainly concentrated (Dahlgren 1980). 

Bicuculline is an isoquinoline alkaloid elaborated from members of the family Fumariaceae (Papaverales), especially in Corydalis, Dicentra, and Fumaria species. Bicuculline, like picrotoxin, is a specific GABA receptor-blocking agent that impedes the... 

Robinson and Sugasawa (8) selected dibenzo[b,g]pyrrocoline for the parent ring system, and this name was adopted for the alkaloid family. The numbering is shown on structure 3 although Robinson used a different pattern. The systematic name for the ring system is indolo[2,l-a]isoquinoline, but di-benzo[ib,g]indolizine also appears in the literature. 

The quinolizidine structure is sometimes found in molecules of complex alkaloids belonging to the indole, isoquinoline, or other families of alkaloids that... 

The pavine and isopavine alkaloids of the Papaveraceae have been discussed in Vols. 4, 10, 12, and 17 of this treatise (2-5), and only brief references have been made to occurrences outside this botanical family. Individual chapters have been devoted to the pavine and isopavine alkaloids in the two books by Shamma (6,7), covering developments until 1977, and also in Rodd s Chemistry of Carbon Compounds (8), published in 1978. A listing of naturally known pavines and isopavines up to 1975, with references to physical and spectral data, appeared in Kametani s Chemistry of the Isoquinoline Alkaloids 9,10). A more recent compilation by Gozler and co-workers 11) has covered references to mid-1982. Relevant literature has also been summarized regularly in Vols. I-XIII of Spe-... 

Papaverine Papaverine, molecular formula C20H21NO4, is an isoquinoline alkaloid isolated from poppy seeds Papaver somniferum, family Papaveraceae). This alkaloid is used mainly in the treatment of spasms and of erectile dysfunction. It is also used as a cerebral and coronary vasodilator. Papaverine may be used as a smooth muscle relaxant in microsurgery. In pharmaceutical preparations, papaverine is used in its salt form, e.g. hydrochloride, codecarboxylate, adenylate and teprosylate. The usual side-effects of papaverine treatment include polymorphic ventricular tachycardia, constipation, increased transaminase levels, hyperbihr-unemia and vertigo. 

The family Lauraceae consists of 50 genera and 2000 species of trees, shrubs, and herbs, of which 70 are of medicinal value in the Asia-Pacific region. Lauraceae are well-known for elaborating isoquinoline alkaloids and sesquiterpenes, the latter most likely representing a vast source of material for the search for NOS. Examples of such compounds are costunolide and dehydrocostunolide found in the leaves of Laurus nobilis (bay leaf, laurel), the leaves of which are widely used as a spice, antiseptic, stomachic, and to treat rheumatism in traditional European medicine (58). The potential of Neolitsea zeylanica Nees (Merr.) as a potential source of NOS inhibitor is discussed here. 

Originally it was intended to list every plant in which these natural isoquinolines are found, documented with a literature reference. The project became unmanageable in that some of the more common alkaloids have been found in literally hundreds of plants. So, in some cases, if there are many species from one Genus, the plant listing will be condensed to mention the particular Genus, the family, plus a literature reference e.g., Corydalis spp. (Papaveraceae) jnp 51, 262 88. This way the broadness of distribution is established. Also, there are... 

Another large group of isoquinoline alkaloids are the alkoxybenzo[a]-phenanthridines. They occur most frequently in the Fumariaceae, the Papaveraceae, and the Rutaceae families. Their close botanical relationship with the... 

Two naphthalene-isoquinoline groups of alkaloids, ancistrocladidine (53) and ancistrotectorine (54), were isolated from Ancistrocladus heyneanus Wall [295], and A. tectorius (Lour.) Merr [296], respectively. The members of the plant family, ancistrocladaceae, are distributed in tropical Asia and Western Africa. Some are regarded as traditionally medicinal plants. The root of A. tectorius has been used to treat dysentery and malaria [296],... 

Cularines are isoquinoline alkaloids, which occur mainly in the Fumaraceae family, and are used as muscle relaxants. Total syntheses of (+)-cularine (171)... 

Species in a relatively small number of herbivorous families dominate the list of plant feeders associated with alkaloid-rich foods. Lepidoptera (butterflies and moths) have catholic tastes when it comes to alkaloid-fortified plants, being represented by the families Nymphalidae (calystegine A-3, pyrrolizidine alkaloids lycopsamine type, harman), Arctiidae (senecionine type), Papilionidae (synephrine, isoquinolines), and Pterophoridae (monoterpene alkaloid rhexifoline).6 In addition, beetles (Chrysomelidae) sequester PAs (senecionine), grasshoppers (Acrididae) store senecionine, and aphids (Aphididae) sequester QAs (sparteine and diterpene alkaloids). 

Benzo[c]phenanthridines are an important class of the isoquinoline alkaloid family. It was possible to synthesize a variety of these compounds based on the S l reactions of appropriate derivatives of o-iodobenzylamines with nucleophiles328. For instance, the pho-tostimulated reaction of 281 (R1 = R2= H, OMe R1 = OPr-/, R2= OMe R R2 = 0CH20) with the appropriate derivative of tetralone enolate ions 284 (R3 = R4 = H, OMe R3 = OMe, R4 = H R3 = OPr-/, R4 = OMe R3R4 = 0CH20) gave the substitution compound, which spontaneously cyclizes to 285 (equation 176). 

---