Spermine alkaloids

Scheme 1.5.8. Spermine alkaloids and their proposed [105] biosynthesis via Michael addition.

Todorova, M., Werner, C. and Hesse, M. 1994. Enzymatic phenol oxidation and polymerization of the spermine alkaloid aphelandrine. Phytochemistry 37, 1251-1256... 

Accumulation and metabolism of the spermine alkaloid aphelandrine in roots of Aphelandra tetragona. Phytochemistry 33, 1033-1036... 

Antimony(m) ethoxide (Sb(OEt)3) promotes the intermolecular amidation of esters and carboxylic acids with amines under azeotropic conditions.47,48 When tetramino esters are used, the antimony(in)-templated intramolecular macrolactamization provides macrocyclic spermine alkaloids in good yields (Equation (14)). Under the same... 

The absolute configurations of two spermine alkaloids, O-methylorantine and aphelandrine, obtained from Chaenorhinum minus and C. villosum, differ only in configuration at C-31,20 as shown in the partial structures (25) and (26). 

Another difficulty is the determination of the homogenity of the isolated alkaloids. To illustrate this two extreme examples are given. By different chromatographic methods and because of its spectral properties (NMR, IR, MS), the natural, approximate 1 1 mixture of the spermidine alkaloids inandenin-12-one and inandenin-13-one appeared to be a pure compound. This was supported by the sharp melting point of its hydrochloride (150- 151°C). Only after chemical degradation was the nature of the mixture determined by mass spectrometry. On the other hand, the behavior of the pure crystalline spermine alkaloid aphelandrine was that of a mixture. At least two criteria were in favor of a mixture. In the H-NMR spectrum... 

Concerning the nature of the polyamine alkaloids, characteristic differences exist. In the case of putrescine alkaloids the base is always a chain in spermidine and spermine alkaloids the cyclic form is predominant. The 13-membered and 17-membered lactams are the preferred rings in the spermidine and spermine alkaloids, respectively. As shown in Scheme 41... 

Spermine alkaloids 252a-c were extracted from the leaves of Dovyalis macrocalyx, a plant belonging to a genus of small trees and shrubs found in Africa and Asia (family Flacourdaceae) <2003OL2793>. 

Hesse, M. and Schmidt, H. (1977) Macrocyclic spermidine and spermine alkaloids. In Wiesner K (Ed.) MTP International Revies of Science, Series 2, Vol. 9, Butterworths, London, 265-307. 

Sb(OEt)3 is highly effective for the metal-templated cyclization of tetramino esters to give macrocyclic spermine alkaloids such as buchnerine, verbacine, verbaskine, and verbascenine (Eq. 3) [9]. The accelerated rates and high regioselectivities suggest a mechanism in which the acyclic tetramino esters are covalently or coordinately attached to the antimony before the final cyclization step. In addition, Sb(OEt)3 is useful as an intermolecular amidation catalyst for reactions between esters or carboxylic acids and amines (Eq. 4) [9]. 

The acetalization of aldehydes and ketones with alcohols is catalyzed by SbCb in the presence of Fe or Al (Scheme 14.5) [21]. The selective acetahzation of aldehydes can also be performed by combined use of Sb(OR)3 (R=Et, iPr) and allyl bromide [26]. Sb(OEt)3 promotes intermolecular amidation between amines and esters or carboxylic acids [27]. When tetraamino esters are used as substrates, the antimony(Ill)-templated macrolactamization occurs to yield macrocychc spermine alkaloids (Scheme 14.6). 

Spermidin and spermin alkaloids, synthesis of 81KPS263, 81YGK1151. 

Macrolactamization Carboxylic esters containing polyamine units undergo cyclization facilitated by preorganization with Sb(OEt)j. Based on the ready preparation of a phenyl-substituted 17-membered lactam by this method in 90% yield, synthesis of several spermine alkaloids (verbacine, verbaskine, and verbascenine) is achieved in a straightforward manner. 

An investigation of the spermine alkaloids present in the roots of several Aphelandra species has indicated that the polyamines putrescine, spermidine, and spermine interconvert, whereas the alkaloid (- -)-aphelandrine (98) content varies considerably during the first year. This is presumed to be due to the need for the diamine precursors to be used to transport cations, especially during bud formation (55). 

The spermine alkaloid chaenorpine (103) has been isolated from Chaen-orhinum minus (Scrophulariaceae) (59). Its structure elucidation was achieved on the basis of chemical degradation and spectroscopic measurements in comparison to the known alkaloid chaenorphine (90). The absolute configuration is depicted as 103. 

Fig. 10. Macrocyclic spermidine and spermine alkaloids from higher plants.

Verbascum alkaioida. Group of macrocyclic "spermine alkaloids from the leaves of Verbascum pseudonobile (Scrophulariaceae), e. g. the main alkaloids (-)-(5)-verbascine and (-)-(5)-verballocine both are glass-like solids, C2gH5gN402, Mr 462.63. 

The number of alkaloids that contain spermine as a partial structure (spermine alkaloids) is less than the number of alkaloids that contain spermidine in their structure (spermidine alkaloHds). Even so, these alkaloids are distributed in eleven plant famihes (i.e., Acanthaceae, Amaranthaceae, Bromeliaceae,... 

The history of the isolation and structure elucidation of the spermine alkaloids dates from 1968, when homaline was isolated from the leaf of Homalium pronyense (Flacourtiaceae). The total synthesis of this alkaloid was reported in 1982, and the chemical structure, including absolute stereochemistry, was confirmed [2]. 

Several plants of the genus Aphelandra (Acanthaceae) also produce spermine alkaloids, and among them, aphelandrine is the main alkaloid. When radioisotope-labeled potential precursors of aphelandrine were fed to Aphelandra tetragona, it was shown that putrescine, spermidine, and cinnamic acid were incorporated into aphelandrine. It was not clear whether spermine was incorporated directly into aphelandrine. Spermine might have been metabolized to putrescine and spermidine before incorporation. It was clarified in this experiment that methionine was the precursor of the 3-aminopropyl moiety of spermidine and spermine [9]. 

Badwani, M. M., K. Bernauer, P. van den Broek, D. Grocer, A. Guogisberg, S. Johne, I. Kompis, F. Schneider, H. Vetth, M. Hesse, and H. Schmid, Macrocyclic spermidine and spermine alkaloids. Pure Appl. Chem., 33, 81-108 (1973). 

Root (maHUANGgen) contains macrocy-clic spermine alkaloids (ephedradines A, B, C, and D) an imidazole alkaloid (feruloyUiista-mine) /-tyrosine betaine (maokonine) and diflavonols (mahuannins A and B) (imm-4 wang). °... 

Rh2(5-DOSP)4 as catalyst and the presence of a chiral auxiliary bound to the diazoacetate derivatives, trans-2,3-dihydrobenzofurans have been prepared in good yields and high diastereoselectivities. This efficient method has been applied to the total syntheses of the complex macrocyclic spermine alkaloid (—)-ephedradine A (orantine) 32, an ypo-tensive component of the crude Chinese drug mao-kon prepared from the roots of Ephedra plants and the penta-cyclic indole alkaloid (—)-serotobenine 33 extracted from Rhaphidophara decursiva ... 

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