Indole alkaloids structures

Quite the most intriguing new indole alkaloidal structural type to appear this year is that of ervatamine (17b) which occurs, together with 20-epi-ervatamine (17c) and 19,20-dehydroervatamine (17a), in Ervatamia orientalis.26a A description of the degradations (Scheme 5) which led to the structural assignments is included in this sub-section on the basis of a possible biogenetic relationship to alkaloids in this class (see below). 

Some of the above considerations led to the proposal which has resulted in this compilation of plant species and the classification according to their contained indole alkaloid structural types. The key to this classification is derived from the recent biosynthetic work of Arigoni (2), Battersby 3, 3a), Leete (4), and Scott (5), and their respective co-workers which, in its infancy when Volume VIII of this series was in publication, now presents conclusive evidence concerning the origin of the complex indole alkaloids in plants 5a). 

Refers to the simple indole alkaloid structural t3qpe c. Fig. 1, p. 5. 

One of the less elaborated indole alkaloid structural variations is typified by ebumamonine (78). A combined chemical and enzymatic route for its synthesis is shown in Scheme 6 (1994T9487, 1990JOC517). Condensation of the enantiopure aldehyde 76 with tryptamine in a classical intramolecular Mannich reaction, with concomitant lactam closure, produced the tetra-cycle 77. 

The indole alkaloid structures typically involve multiple ring... 

The Pictet-Spengler condensation has been of vital importance in the synthesis of numerous P-carboline and isoquinoline compounds in addition to its use in the formation of alkaloid natural products of complex structure. A tandem retro-aldol and Pictet-Spengler sequence was utilized in a concise and enantioselective synthesis of 18-pseudoyohimbone. Amine 49 cyclized under acidic conditions to give the condensation product 50 in good yield. Deprotection of the ketone produced the indole alkaloid 51. 

A second direct route to an extended 3,4-dihydro-j8-carbolinium system (120) using the Bischler-Napieralski ring closure is based on the cyclization of intermediates of general structure 118. Three approaches to intermediates of this type have been developed in connection with stereospecific syntheses in the indole alkaloid field. The first approach, introduced independently by Stork and Hill and by van Tamelen and co-workers and often used... 

Hi) Dehydrogenation. j3-Carboline derivatives may be obtained from tetrahydro-)3-carbohnes by zinc dust distillation or high temperatmre dehydrogenation with selenium or palladium black. Many of the complex indole alkaloids may be degraded, with bond cleavage, to yield simple )3-carbolines under these conditions and this approach has become a standard method in structural elucidations. Examples are numerous but outside the scope of this review. 

As a result, we could open the door to a new frontier in indole chemistry. Various 1-hydroxyindoles (4a), l-hydroxytryptophans(la), 1-hydroxytryptamines (lb), and their derivatives have been given birth for the first time. As predicted, 1-hydroxytryptophan and 1-hydroxytryptamine derivatives are found to undergo previously unknown nucleophilic substitution reactions. In addition, we have been uncovering many interesting reactivities characteristic of 1-hydroxyindole structures. From the synthetic point of view, useful building blocks for indole alkaloids, hither to inaccessible by the well-known electrophilic reactions in indole chemistry, have now become readily available. Many biologically interesting compounds have been prepared as well. 

Fig. 31. Example of neuroactive indole alkaloids from plants. Note the similitude of chemical structure of harmine, harmaline, and serotonin.

Having an efficient total synthesis of the indole alkaloid vindoline in mind, the Boger group [47] developed a facile entry to its core structure using a domino [4+2]/[3+2] cycloaddition. Reaction of the 1,3,4-oxadiazoles 4-139 led to 4-140 in high yield and excellent stereoselectivity via the intermediates 4-141 and 4-142 (Scheme 4.29). 

The pyrrolonaphthyridines 208 and 209 can be prepared from rearrangement of the pentacycle 207 upon treatment with trifluoroacetic acid (TFA) (Scheme 52). These products are of interest as they have the same structural skeleton as the indole alkaloid (—)-goniomitine, isolated from the root bark of Gonioma Malagasy <1995JOC3282>. Compound 208 has since been used in the synthesis of further derivatives which show cytotoxic activity against leukemia cells <2001BML79>. 

Secoiridoids are complex phenols produced from the secondary metabolism of terpenes as precursors of several indole alkaloids (Soler-Rivas and others 2000). They are characterized by the presence of elenolic acid, in its glucosidic or aglyconic form, in their molecular structure. Oleuropein, the best-known secoiridoid, is a heterosidic ester of elenolic acid and 3,4- dihydroxyphenylethanol containing a molecule of glucose, the hydrolysis of which yields elenolic acid and hydroxytyrosol (Soler-Rivas and others 2000). 

Indole alkaloids from Tabernaemontana plants are all biogenetically derived from tryptophan (tryptamine) and secologanine, which constitute the indole and terpenic portions, respectively, and can be classified into nine main types depending on the structural characteristics of their skeleton (Fig. 1). 

Fig. 2. Structural formulas of indole alkaloids isolated from Tabernaemontana plants.

During the past two decades a great number of papers have been published on the isolation, structure elucidation, synthesis and transformation, biogenesis, chemotaxonomy, and pharmacology of indole alkaloids. In this chapter we summarize the new results that appeared from 1968 to mid 1984 for the cory-nantheine-yohimbine group of monoterpene indole alkaloids with greater emphasis on their chemistry, excluding the related oxindoles and heteroyohimbines. 

Two important books on the biogenesis of indole alkaloids have been published (5, 6), therefore we do not intend to cover the literature of the biogenesis of corynantheine- and yohimbine-type alkaloids. Our chapter begins with the structure elucidation of the alkaloids isolated during the past two decades and proceeds with the synthesis, transformation, as well as spectroscopy of the alkaloids in question. 

Geissoschizine (30) (7) is one of the most widely investigated monoterpene indole alkaloids. Since the first structure elucidation, carried out by Rapoport... 

Since the last major review of the biosynthesis of the monoterpenoid indole alkaloids (97), there have been several full and partial 98-104) reviews of various aspects of the work that has been conducted since 1974. Two major developments have dominated the field in this period, namely, the demonstrations that (i) strictosidine (33) is the universal precursor of the monoterpenoid indole alkaloids and (ii) selected cell-free systems of C. roseus have the ability to produce the full range of alkaloid structure types, including the bisindoles. This section traces some aspects of these developments, paying particular attention to work been carried out with C. roseus, and omitting work, important though it may be, on other monoterpenoid indole alkaloid-producing plants, e.g., Rauwolfia, Campto-theca, and Cinchona. 

Scheme 41 Synthesis of polycyclic indole alkaloid-type compounds 225. The X-ray structure of compound 225D is shown in blue sticks (CCDC-749252)...

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