Alkaloids imidazole

A review on imidazoles, covering their chemical and physical pro- 

R = Me, r2 = COPh) and the new alkaloids N-l-demethyIcynometrine (6 R = R = H) and N-l-demethylcynodine (6 R = H, = COPh) the absolute configuration of the alkaloids is as shown and that of isocynometrine (from Cynometra lujae) is (7). N-Cinnam.oylhistidine has been isolated from the leaves of Lycium cestroides. The betaine clithioneine (8) has been identified as a constituent of 

Natural products that contain the imidazole nucleus have been found in such diverse sources as mushrooms and broiled fish. In the former, the fresh fruiting bodies of Clitocybe acromelalga contain the new amino-acid betaine clithioneine 

A synthesis of the imidazole alkaloid dolichotheline (11) (and of other amide-containing alkaloids) has been reported 3-acyl-thiazolidine-3-thiones are used in an aminolysis procedure.8 

Many frogs contain high levels of N-methyihistamine and V,7V-dimethyl-histamine in their skin. Although such simple methylated derivatives can be considered alkaloids, they will not be treated as such in this review (see Refs. 1 and 5 for structures and tabulation of occurrence in amphibians). 

Spinceamine (XXI) and 6-methylspinceamine (XXII) occur in amphibians (177-180) and represent cyclized analogs of histamine and V-methylhistamine, respectively. The spinceamines readily form by the reaction of formaldehyde with histamine or N-methylhistamine (see Ref. 

Morphine (XXIII), a well-known plant alkaloid, has been detected in trace amounts in the skin of the bufonid toad, Bufo marinus (184). It is possible that this, and perhaps other trace alkaloids found in amphibian 

A general review on the use of electrochemical methods for the synthesis of N-heterocycles and natural products includes a section on imidazole derivatives. Thin-layer chromatographic methods for the separation of imidazole alkaloids have been briefly reviewed. Pharmacological effects of pilocarpine (15) have been summarized as part of an excellent review on convulsant alkaloids.  

7V -rrans-Cinnamoylhistamine (16) has been identified in Acacia spirorbis The alkaloid referred to as metapilocarpine has been shown to be identical with ( )-isopilocarpine (17). Its pharmacological effects were found to be similar to that of pilocarpine (15). 

The conflict (see Vol. 5 of these Reports) concerning the absolute stereochemistry of ( )-isopilosine (25, 3/ , 6R) (18) and (—)-epi-isopilosine (25, 3/ , 65) (19) has been resolved in favour of these absolute stereoformulae on the basis of high-dilution i.r. studies.  

A number of pilocarpine salts (23 X = O or NOH R = NO2, Br, CeHs, or F) have been subjected to D2O exchange experiments in [ HejDMSO and under basic conditions. Compounds (23 X = 0) showed rapid exchange of the a-CH2CO protons. In contrast, oxime derivatives (23 X = NOH) exhibited exchange at C-2, 

Comparative visual and potentiometric titrations of salts of pilocarpine have been reported. The structurally interesting spinaceamine (24 R = H) and 6-methylspinaceamine (24 R = Me), isolated from amphibian venoms, have been shown to possess antimicrobial activity.  

Noordam, L. Maat, and H. C. Beyerman, Reel. Trav. Chim. Pays-Bas, 1979, 98, 467. 

A new Pilocarpus alkaloid, epi-isopiloturine, has been isolated from Pilocarpus microphyllus -, its structure (15) was elucidated by C n.m.r. spectroscopy and by its conversion into neopilosine and anhydropitoturine. N-Methylmurexine (16 R = Me) has been reported to occur in the marine gastropod mollusc Nucella 

L-N-Methylhistidine (20 R = Me) or its ethyl counterpart (20 R = Et) can be prepared by treating carhoxy-methylhistidine (18) with NN -carbonyldi-imidazole to give the imidazo[l,5-c]pyrimidine (19) this, upon alkylation (with RI) followed by hydrolysis (with 6M-HC1) gives the N-alkyl-histidine (20 R = Me or Et). 

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Examples of alkaloid of relative pharmaceutical usefulness so far characterized from Rutaceae are pilocarpine from Pilocarpus jaborandi Holmes. This imidazole alkaloid is occasionally used to treat glaucoma. 

Myer and Kock reported a study of several tetracyclic pyrrole-imidazole alkaloids isolated from marine sponges in 2008 that extensively utilized... 

L-histidine Imidazole alkaloids Imidazole Histamine Pilocarpine Pilosine... 

L-isoleucine L-leucine L-lysine Lysine-derived alkaloids Imidazole alkaloids Manzamine alkaloids True alkaloids... 

Mauritamide A (481), a taurine-containing metabolite, was isolated from the sponge Agelas mauritiana [411]. The taurine-containing alkaloids tauroacidins A (482) and B (483) were isolated from a Hymeniacidon sp. from Okinawa and are tyrosine kinase inhibitors [412]. An imidazole alkaloid, (9 )-clathridine 9-A-(2-sulfoethyl)-imine (484), a taurine derivative of clathridine, was isolated from the calcareous sponge... 

The pyrrole-imidazole alkaloid taurodispacamide A (486) has been isolated from the Mediterranean sponge Agelas oroides. The structure was established from spectroscopic data. Taurodispacamide A (486) exhibited antihistaminic activity when tested on guinea pig ileum [415]. 

Hoffmann H, Lindel T (2003) Synthesis of the Pyrrole-Imidazole Alkaloids. Synthesis 1753... 

Fattorusso E, Taglialatela-Scafati (2000) Two Novel Pyrrole-Imidazole Alkaloids from the Mediterranean Sponge Agelas oroides. Tetrahedron Lett 41 9917... 

Lindel T, Hochgiirtel M, Assmann M, Kock M (2000) Synthesis of the Marine Natural Product Wa-(4-Bromopyrrolyl-2-carbonyl)-L-homoarginine, a Putative Biogenetic Precursor of the Pyrrole-Imidazole Alkaloids. J Nat Prod 63 1566... 

Grube A, Kock M (2006) Stylissadines A and B The First Tetrameric Pyrrole-Imidazole Alkaloids. Org Lett 8 4675... 

Urban S, de Almeida Leone P, Carroll AR, Fechner GA, Smith J, Hooper JNA, Quinn RJ (1999) Axinellamines A-D, Novel Imidazo-Azolo-Imidazole Alkaloids from the Australian Marine Sponge Axinella sp. J Org Chem 64 731... 

Rahbaek L, Anthoni U, Christophersen C, Nielsen PH, Petersen BO (1996) Marine Alkaloids. 18. Securamines and Securines, Halogenated Indole-Imidazole Alkaloids from the Marine Bryozoan Securiflustra securifrons. J Org Chem 61 887... 

Mourabit AA, Potier P (2001) Sponge s Molecular Diversity Through the Ambivalent Reactivity of 2-Aminoimidazole A Universal Chemical Pathway to the Oroidin-Based Pyrrole-Imidazole Alkaloids and Their Palau amine Congeners. Eur J Org Chem 237... 

Lindel T, Hoffmann H, Hochgiirtel M, Pawlik JR (2000) Structure-Activity Relationship of Inhibition of Fish Feeding by Sponge-Derived and Synthetic Pyrrole-Imidazole Alkaloids. J Chem Ecol 26 1477... 

Histidine is a proven precursor of dolichothe-line (Figure 6.111) in Dolichothele sphaerica (Cactaceae), the remaining carbon atoms originating from leucine via isovaleric acid (see page 197). The imidazole alkaloids found in... 

Maat L and Beyerman HC (1983) The imidazole alkaloids. The Alkaloids, Chemistry and Pharmacology (ed Brossi A) Vol 22. Academic, San Diego, pp 282-331. 

Nine 2-amino imidazole alkaloids were isolated from a Red Sea calcareous sponge, Leucetta chagosensis (50,51). They belong to four differ-... 

Three imidazole alkaloids have been isolated from this plant. Their structures were ascertained largely by spectral methods and confirmed wholly or partly by limited chemical reactions anantine (C15H15ON3 mp 204° [a]D —549 W-acetyl, mp 99°) (69) cynometrine... 

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