Indole plant alkaloids

Alkaloids are compounds that contain nitrogen in a heterocyclic ring and are commonly found in about 15-20% of all vascular plants. Alkaloids are subclassified on the basis of the chemical type of their nitrogen-containing ring. They are formed as secondary metabolites from amino acids and usually present a bitter taste accompanied by toxicity that should help to repel insects and herbivores. Alkaloids are found in seeds, leaves, and roots of plants such as coffee beans, guarana seeds, cocoa beans, mate tea leaves, peppermint leaves, coca leaves, and many other plant sources. The most common alkaloids are caffeine, theophylline, nicotine, codeine, and indole... 

Salutaridinol 7-0-acetyltransferase catalyzes the conversion of the phenanthrene alkaloid salutaridinol to salutaridinol-7-Oacetate, the immediate precursor of thebaine along the morphine biosynthetic pathway in P. somniferum (Fig. 10.7).26 Acetyl CoA-dependent acetyltransferases have an important role in plant alkaloid metabolism. They are involved in the synthesis of monoterpenoid indole alkaloids in medicinal plant species such as Rauwolfia serpentina. In this plant, the enzyme vinorine synthase transfers an acetyl group from acetyl CoA to 16-epi-vellosimine to form vinorine. This acetyl transfer is accompanied by a concomitant skeletal rearrangement from the sarpagan- to the ajmalan-type (reviewed in2). An acetyl CoA-dependent acetyltransferase also participates in vindoline biosynthesis in Catharanthus roseus, the source of the chemotherapeutic dimeric indole alkaloid vinblastine (reviewed in2). Acetyl CoA deacetylvindoline 4-O-acetyltransferase catalyzes the last step in vindoline biosynthesis. A cDNA encoding acetyl CoA deacetylvindoline 4-0-acetyltransferase was recently successfully isolated.27... 

The binary indole-indoline alkaloids vinblastine (VLB, 1) and vincristine (VCR, 2) (Fig. 1) have triggered considerable chemical investigation as a result of their extensive clinical use as antineoplastic agents (2-4), coupled with an arduous isolation from plant material, and because of... 

The real breakthrough toward synthesis of vinblastine and, in fact, the first significant laboratory preparation of binary indole-indoline alkaloids with the natural C-16 -C14 PARF configuration, was due to the work of the Potier-Langlois team at Gif (38,39 for reviews, see Refs. 40 and 41), buttressed by results obtained by the Kutney group in Vancouver (42,43,44), and the efforts of Atta-ur-Rahman and associates in Karachi. Their basic idea, which relied on the biogenetic consideration that binary indole-indoline alkaloids are formed in plants by the union of vindoline... 

One of the major subdivisions of plant alkaloids is termed the indole alkaloid group. All contain the basic indole heterocycle, and many have valuable pharmacological activity that can be exploited in drug materials. The indole portion is very often fused to another heterocycle we shall see some typical stractures in Section 11.9, where we shall consider them under fused heterocycles. 

Within the natural products field, the investigation of complete biosynthetic pathways at the enzyme level has been especially successful for plant alkaloids of the monoterpenoid indole alkaloid family generated from the monoterpene gluco-side secologanin and decarboxylation product of tryptophan, tryptamine [3-5]. The most comprehensive enzymatic data are now available for the alkaloids ajmalicine (raubasine) from Catharanthus roseus, and for ajmaline from Indian Rauvolfia serpentina [6] the latter alkaloid with a six-membered ring system bearing nine chiral carbon atoms. Entymatic data exsist also for vindoline, the vincaleucoblastin (VLB) precursor for which some studies on enzymatic coupling of vindoline and catharanthine exist in order to get the so-called dimeric Catharanthus indole-alkaloids VLB or vincristine [7-9] with pronounced anti-cancer activity [10, 11]. 

Material Yohimbine is one of several indole-based alkaloids found in Corynanthe yohimbe, Rauwolfia serpentina, and several other plants. 

All these indolic plant hormones or hormone precursors are likely to arise from tryptophan. Other reactions of trytophan, for example, in alkaloid l)iogenesis, are discussed in the next section. 

A time-resolved study of the decay kinetics of transient radicals produced from 2,2,4,6-tetramethyl-l,2-dihydroquinoIine in both aqueous and micellar solution has appeared, and sanguinarine, a benzophenanthridine plant alkaloid, has been photooxidised to oxysanguinarine in an irreversible singlet state process. Pyrrolo-[2,3-b]indole (77) has been produced with some enantioselectivity by photosensitized oxygenation of Nb-(methoxycarbonyl)tryptamine in the presence of (-)-nicotine, and irradiation of 3-methylindole on a CdS surface and under... 

The myriad indole-containing plant alkaloids of the indoloquinolizidine type and other types are not covered. The list of simple indole, pyrrole, and carbazole plant alkaloids, which is discussed here, is far shorter. 

Several anticancer drugs are indoles, the most famous of which are the Catharanthus roseus plant alkaloids vinblastine (124) and vincristine (125) (Scheme 18), both of which continue to be important drugs for the treatment of Hodgkin s disease, childhood leukemia, and other cancers [141-143], The rebeccamycin analogue NSC-655649 (126) is in phase n trials for the treatment of metastatic renal cell cancer... 

As we encountered earlier, Fischer indole synthesis methodology has been used to synthesize the plant alkaloid rutaecarpine (110) and many analogues of this COX-2 inhibitor. Several examples are shown in Scheme 45. Equation 1 is a simple synthesis of rutaecarpine itself [332]. This plant alkaloid, found in Evodia rutaecarpa, has long been used in Asian folk medicine for treating inflammation. The plant Wu-Chu-Yu has been employed as a remedy for gastrointestinal disorders, headache, dysentery, and postpartum hemorrhage. Several halogenated and... 

Indole and its derivatives are found in many natural products as plant alkaloids that have antimicrobial [150], anti-inflammatory [151], antibacterial [152], and antidepressive activities. Many sulfur-containing compounds such as sulfates, sulfones, and sulfonomides exhibit insecticidal, germicidal, antimicrobial, and antibacterial activities [153,154] and certain phenyl sulfones show fungicidal properties [155]. 

To date, biosynthetic pathway for four classes of plant alkaloids has been characterized to some extent the benzylisoquinoline, monoterpenoid indole, purine, and tropane alkaloids. Benzylisoquinoline alkaloids (BIAs) are derived from tyrosine and are comprised of 2,500 defined structures found mainly in the Papaveraceae, Ranunculaceae, Berberidaceae, and Menispermaceae [11]. First step of BIA biosynthesis begins with the stereoselective Pictet-Spengler condensation of dopamine and 4-hydroxyphenylacetaldehyde to form (5)-norcoclaurine. Subsequently, through a series of methylations and hydroxylations, (5)-norcoclaurine gets converted into (5)-reticuline, which is the pivotal intermediate for many pharmaceutically important BIAs formed further down in the pathway (i.e., downstream pathways) (Fig. 8.6) [3]. 

The 1-benzyltetrahydroisoquinoline skeleton is one of preeminence in the elaboration of plant alkaloids. Only the terpenoid indole skeleton (Section 6.6.2) appears in more diversely modified form. Among the benzylisoquinolines, reticuline (6.127) is of outstanding importance as a substrate for modification. Formation of the... 

The terpenoid indole skeleton is the most widely found amongst the plant alkaloids, the number of known examples exceeding one thousand. As seen in e.g. ajmalicine 6.243) these alkaloids are constituted from a tryptamine unit (proved to derive from tryptophan and tryptamine [170]) and a C9 or Cjq unit which, after much experimentation, was proved to be terpenoid in origin. [Examination of 6.243) shows this is not immediately obvious.]... 

The 1-benzyltetrahydroisoquinoline skeleton is a very important one in the field of plant alkaloids and is the subject of various, interesting modifications. Indeed, with the exception of terpenoid indole alkaloids, no other skeleton is so diversely modified. In this family of benzylisoquinolines, reticuline (25) is preeminent, being a key intermediate in the biosynthesis of many alkaloids. 

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