Corynanthe-type alkaloids

A series of publications appeared regarding the transformation of corynanthe-type alkaloids to yohimbane derivatives (285-287). The saponification of cory-nantheine (52) in methanol yielded a complex mixture of corynantheic acid (588), two C-16-epimer acetal acids (589), and demethoxycarbonylcory-nantheine (590). All four compounds upon hydrolysis in acid resulted in cory-... 

Aspidosperma alkaloids These alkaloids have an aspidosperma-type nucleus. The a and are the same as in corynanthe type. Catharantine is the P4 from cathenamine (Figure 68). 

Pictet-Spengler isoquinoline synthesis. The final steps in a synthesis of (—)-antirhine (2), a Corynanthe-type indole alkaloid, involved partial reduction of the lactam 1 to a hemiamina), which cyclizes to 2 in the presence of dilute HC1,2... 

Alkaloids like preakuammicine (Figure 6.79) and akuammicine (Figure 6.75) contain the C10 and C9 Corynanthe type terpenoid units respectively. They are, however, representatives of a subgroup of Corynanthe alkaloids termed the Strychnos type because of their structural similarity to many of the alkaloids found in Strychnos... 

For (essentially) the first time recently, strains of C. roseus cultures have been obtained which will synthesize Strychnos, Iboga, and Aspidosperma alkaloids.34 This opens up the exciting possibility of studying the biosynthesis of those alkaloids lying beyond the Corynanthe type, such as (102), by using enzyme preparations from tissue cultures, which have proved so powerful for the early stages of biosynthesis (see above). 

Ajmalicine, 19-epi-ajmalicine and tetrahydroalstonine are formed from 4,21-dehydrogeissoschizine via cathenamine (Fig. 2.9). The enzymatic synthesis of these corynanthe-type alkaloids has been investigated using C. roseus cell suspension cultures, and the enzymes involved have been reviewed by De Luca (1993) and Ziegler and Facchini (2008). Ajmalicine can be oxidized by POD to serpentine. This reaction may take in the vacuole. 

The proposal that the next stages of the pathway would involve intermediates of the Corynanthe type has received experimental support. Corynanthealdehyde (12) was not incorporated but the closely related corynantheal (13) did serve as an efficient precursor for all three Cinchona bases.12 Thus, the close parallel between the early stages of quinine biosynthesis and the corresponding stages (Scheme 1) of indole alkaloid biosynthesis is established. 

Roxburghines constitute a group of octacyclic sesquimeric indole alkaloids conceptually derived from two tryptamine molecules and a monoter-pene moiety of the corynanthe type. Roxburghine D (171) and the new analog, roxburghine X (172), C31H32N4O2, mp 215°C, [a]D27 -29°,... 

The asymmetric synthesis of 6-lactone 8, a key intermediate for (-)-antirhine (a Corynanthe-type indole alkaloid)998 from optically pure alcohol 5a (>99% Z) involves such a type of Cope rearrangement969. The anionic oxy-Cope rearrangement of 6a under the standard conditions yields the erythro-yxoduct 7a with 80% de and 84% ee. 

The isolation of cordifoline and related bases led to the prediction of the existence of a common precursor derived by condensation between tryptophan and secologanin. This tetrahydrodeoxycordifoline (TDC) could be (a) a biogenetic cul-de-sac (b) an alternative intermediate to vincoside for some terpenoid indole alkaloids, or (c) the progenitor of a novel range of acidic terpenoid indole alkaloids in which the carboxy group of tryptophan was retained. The last possibility stimulated a search for such alkaloids which was amply rewarded by the discovery in A. rubescens of adirubine (7), 5a-carboxytetrahydroalstonine (102), and 5a-carboxycorynanthine (103), shown to have the tryptophan-based Corynanthe type structures 189,190, and 191, respectively. Surely, with the adoption of modern techniques for... 

Table II tabulates the plant species which contain the complex indole alkaloids. The letters in this table correspond to the various structural types as coded in Figs. 2 and 3. Types I, II, and III are the major variations of the Cfl-Ci 0 unit which, in combination with tryptamine, formally elaborate the three significantly different groups of complex indole alkaloids Corynanthe, Iboga, and Aspidosperma. Such initial classification follows the outline set by Battersby [3, 3a) and others (2, 4, 5). The...

Sarpagine-type indole alkaloids have a structural feature bonding the C-5 and C-16 positions in the Corynanthe-typ monoterpenoid indole alkaloids. This type of compound is distributed not only in Gelsemium plants, but also in many genera in the family of Apocynaceae, Rubiaceae, and Loganiaceae. As shown in Table I, sfac sarpagine-type alkaloids 1-3, 5, 8, and 9 have been isolated from the Gelsemium plants. 

Pawelka and Stockigt (5S5) identified eight different indole alkaloids from cell suspension cultures of O. elliptica. The pattern of the alkaloids found was quite different from the above-mentioned results reported by Kuoadio and co-workers (779). The alkaloids identified were tetrahydroal-stonine, cathenamine, pleiocarpamine and two other methoxy-substituted heteroyohimbine alkaloids Corynanthe/heteroyohimbine type), norfluo-rocurarine Strychnos type), and apparicine and epchrosine Aspi-dosperma type). The last mentioned alkaloid was a new compound (729) not known from intact plants. 

Chemistry of indole alkaloids related to the corynanthe-type from Uncaria, Nauclea, and Mitragyna plants 05COC1445. 

Intramolecular ene reactions. Use of Lewis acid catalysts (particularly FeCL, 15,156 16,190-101) has greatly extended the usefulness of intramolecular ene cy-clization. Thus a new diastereoselective route to corynanthe-type alkaloids involves the ene cyclization of 1 to tr s-indolo[2,3-a]-quinolizidine (2), a precursor to methyl corynantheate (3) by demethoxycarbonylation. SnCU (1 equiv.) is the only common Lewis acid that is useful for this particular ene cyclization, and even so, it also requires the presence of trifluoroacetic acid (1.5 equiv.). 

III. Tr5 tamine-Tryptamine Type with an Additional Monoterpene Unit and Related Alkaloids rV. Corynanthe-Tryptamine Type V. Corynanthe-Corynanthe Type VI. Coryn nthe-Strychnos Type... 

These alkaloids possess quinoline and quinuclidine skeleta, and it was established that the precursor of the quinoline moiety of these alkaloids is tryptophan, as in the case of the indole alkaloids. It was further established that the remaining carbon framework was derived from the C9 unit of corynanthe type Cjo unit (geraniol, section 2.9). 

Fig. 261. Transformation of ajmalicine to alkaloids with Corynanthe-type, Iboga-type, and Aspidosperma-type skeletons...

It is now considered [188 b, 188 c] that stemmadenine (XLIIA, Fig. 3) is likely to be a key intermediate between alkaloids of the Corynanthe type and the Ihoga and Aspidosperma types although whether it is a precursor [188b, 188 c] or further derivative [187a] of the Strychnos type skeleton is still unsettled. 

Two new indole alkaloids, bisnicalaterine D (1), consisting of an ebumane and a corynanthe type of skeletons, and nicalaterine A (2) were isolated from the bark of Hunteria zeylanica. Their structures were elucidated by various spectroscopic data such as NMR and CD spectra. A series of bisnicalaterines and nicalaterine A showed potent anti-plasmodial activity against P. falciparum 3D7 [28]. 

The alkaloids imder discussion share a common Corynanthe-type nucleus derived from secologanin. Yohimbine is a carbocyclic variant of ajmalicine, and the enzymes that convert deglycosylated strictosidine to yohimbine have not been identified [124, 125]. Strychnine and bmcine are synthesized from the preakuammicine structure by hydrolysis, decarboxylation, and condensation reactions to aldehyde (Wieland-Gumlich), and subsequently reaction with acetyl-CoA to make a hemiacetal form of aldehyde (Wieland-Gumlich) and strychnine and brucine. Brucine is a dimethoxy form of strychnine. Ellipticine is a representative member of pyrido[4,3-b] carbozole alkaloid, and the formation of ellipticine is from ajmalicine (corynanthean skeleton) [126] (Fig. 20.8). 

When the aldehyde partner of the Pictet-Spengler reaction with tryptamine is the terpene secologanin, strictosidine is formed as an entry toward the vast monoterpene indole alkaloids [32, 33]. Hydrolysis of the glucosidic part releases the strictosidine aglycone bearing an aldehyde, while imin-ium formation and further cyclization and reduction can lead to ajmalicine (from oxocyclization) or yohimbine (from car-bocyclization). These alkaloids are referred to as from the Corynanthe type, with the monoterpene carbon skeleton unmodified. Although it misses one carbon and has a very... 

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