Holarrhena alkaloids

Triterpene (Steroid) Solanum alkaloids Veratrum alkaloids Funtumia alkaloids Holarrhena alkaloids Buxus alkaloids Salamander alkaloids... 

Holarrhena spp., alkaloids, 742 pharmacological action, 748 Holarrhenine holarrhine, 743, 747 holarrhimine, 742, 743, 747 Homatropine, 74... 

More complex compounds containing enamine grouping, e.g., holarrhena alkaloids such as conkurchine and conessidine, possess an endocyclic rather than exocyclic double bond (159). On the other hand, 1 -methyl-2-alky Ipiperi-... 

The stem bark of Holarrhena antidysenterica Wall. (Apocynaceae) yielded the known steroidal alkaloids holarrhimine, isoconessimine, and conimine (108). Leaves of Holarrhena curtisii King et Gamble yielded the known as well as new aminoglycosteroidal alkaloids holacurtine (102) and N-demethylholacurtine (103), respectively (109). 

Carbon source was found to be a significant factor in plant cell metabolism [34 - 39], which affected the accumulation of alkaloids by suspension cultures of Holarrhena antidysenterica [36], of anthocyanins by Vitis vinifera cell suspen-... 

Nitrogen source is also very important for plant cell metabolite formation, as reported in suspension cultures of Holarrhena antidysenterica for accumulation of alkaloids [36], in cell suspensions of Vitis vinifera for anthocyanin formation [37], and in shikonin production by Lithospermum erythrorhizon cell cultures [38]. 

A new alkaloid, holacetine (la), has been isolated in 0.04% yield from the root bark of Holarrhena antidysenterica, together with the known component cones-sine.1 Acetylation of holacetine gave an O-acetyl derivative (lb), vigorous acid-catalysed hydrolysis of which yielded the (20S)-20-amino-pregnane (lc). The identity of the latter, and hence of holacetine, was established by its conversion via standard methods into the known alkaloid funtumafrine C (2), and by its preparation from (20S)-3/3-hydroxypregn-5-ene-20-carboxylic acid.1 Conessine has been identified in tissue cultures of H. antidysenterica.2... 

Extraction of the leaves of Holarrhena curtisii that had grown in Thailand yielded the known constituent holacurtine (6a) together with a new alkaloid.6 The latter was assigned the structure A-desmethylholacurtine (6b) on the basis of spectroscopic comparison with holacurtine. The H n.m.r. spectrum of A -acetyl-holacurtine (6c) showed two resonances each for the 0-methyl, A-methyl, and secondary C-methyl groups, which was interpreted to mean that the amide group... 

The fission mechanisms assigned were proved by labeling.168 The proposed structure of a-hydroxyconnessine was confirmed by mass spectrometry166 and several steroidal alkaloids occurring in Holarrhena could be detected and identified.170... 

An alkaloid obtained from the seeds of Holarrhena antidysenterica (Apocynaceae). 

The steroidal alkaloids have a nucleus based on 21, 24, or 27 carbon atoms (Fig. 44). The C21 alkaloids are pregnane-derived with nitrogen inserted at C-3, at C-20, or at both positions. They are characteristic of the Apocynaceae Funtumia and Holarrhena species) and the Buxaceae Buxus species). The Buxaceae also produces C24 alkaloids based on the cycloartane skeleton. The most interesting alkaloids are those in the Solanaceae and the Liliaceae. These are C27 alkaloids, and examples include solasodine and solanidine many derivatives are glycosylated. The alkaloids from the Liliaceae, such as veratramine of the white hellebore (Veratrum album), were formerly used for cardiac... 

Steroid alkaloids were also found in Funtumia and Malouetia. The genus Funtumia comprises tropical trees indigenous to equatorial and West Afrika. Alkaloids found therein belong to types I and II. Many contain only one atom of nitrogen and an oxygen function in positions 3 or 20 in comparison Holarrhena alkaloids exhibit this type of substitution much less frequently. 

The genus Malouetia occurs in both Africa and South America. It is distinguished by the same types of alkaloids as Funtumia and Holarrhena. Of particular interest is the isolation of the quaternary alkaloid malouet-ine with curarizing effect in the African Malouetia, bequaertiana Woods. It is probable that the same effect produced by the Venezuelan drug guachamacd can be attributed to some alkaloids of the South American Malouetia (3). 

The mass spectrometric investigation of a series of Holarrhena alkaloids was independently undertaken by two groups (10,11 see also 12, 13). Their work resulted in practically identical conclusions and also demonstrated the immense diagnostic value of mass spectrometry in this field of alkaloid chemistry. 

Since the appearance of a summary of Holarrhena alkaloids in Volume VII of this series, several partial and three total syntheses of conessine (or related bases) have been published. 

The fact that most of the Holarrhena alkaloids are characterized by substitution in position 18 was utilized for preparation of a series of nitrogen-free, 18-substituted steroids, which are of interest in relation to the adrenocortical hormone aldosterone. A detailed description would be beyond the scope of this summary. However, since some steps in these syntheses constitute interesting reactions of Holarrhena alkaloids, a brief outline, dealing with the principles of these procedures, will be presented here. 

No investigation dealing with the biogenesis of Pachysandra or Sar-cococca alkaloids has been reported. However, their close similarity to Holarrhena alkaloids permits the assumption of analogous biosynthetic pathways. It may be noted that important questions concerning the biogenesis of steroidal Apocynaceae and Buxaceae bases remain still open. 

Note added in proof The structures of neoconessine 240), epipachysandrine-A 241), several new alkaloids from Buxus microphylla 242), and of artifacts arising on methy-lation of the alkaloids from Holarrhena antidysenterica 24 ) have been established. The reactions of Eschweiler methylation productsof 16 S aininoparava]larine derivatives have been studied 244). 

A new alkaloid holacetine (8) occurs in the root bark of Holarrhena antidysenterioa its structure has been settled by chemical correlation with the known funtumafrine C (R. N. Rej et al., Phytochem., 1976, 1, 1173). 

The extracts of the plants of the genus Holarrhena have been used in the Ayurvedic medicine for over 1500 years in the Indian subcontinent for the treatment of parasitic infections. An important plant of this class is H. antidysenterica, whose bark has been used to treat amoebic dysentery in man. The extract of the bark of this plant, called kurchi, conessi or telicherry bark, contains several alkaloids of which the major one is conessine (8) [32,33]. This alkaloid has been used in the treatment of intestinal and extraintestinal amoebiasis in humans [34,35]. However, neither conessine nor its structural analogues find use in the modern therapy of human amoebiasis [36]. 

---