Sesquiterpene pyridine alkaloids

Compounds belonging to this group of alkaloids are sourced from the Celas-traceae and Hippocrateaceae families and contain the sesquiterpene nucleus. More than 220 alkaloids are known in this groups. Sesquiterpene pyridine 

Claisen reaction neophilic addition dehydration and enoiization 

Non-celastraceous sesquiterpene pyridine alkaloids are those compounds which have been isolated from other plants not belonging to the Celestraceae family. Rotundine, for example, has been isolated from Cyperus rotun-dus (Cypraceae). This is a structurally interesting alkaloid because it has a sesquiterpene skeleton containing a cyclopentane ring attached to the pyridine ring . 

The sesquiterpene pyridine alkaloids have antifeedant and insecticidal activ-ihes. Some alkaloids, such as triptonine B, hypoglaunine B, hyponine B and wilfortrine, have antivirus activity potential. Others, such as emarginatines A-B, E-G and emarginatine, have cytotoxic activity. Ebenifoline and cangorinine have immunosuppressive activity. 

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Senecio alkaloids, see Pyrrolizidine alkaloids Sesquiterpene pyridine alkaloids, 60, 287 (2003)... 

Nicotinic acid Nicotinic acid-derived alkaloids True alkaloids Pyridine alkaloids Sesquiterpene pyridine alkaloids... 

Natural sesquiterpene pyridine alkaloid formation needs two precursors, one for the pyridinium moiety and another for the sesquiterpene moiety. The a for formation of the pyridinium moiety is nicotinic acid, which reacts with isoleucine and, by oxidative reaction, produces evoninic acid, wilfordic acid or edulinic acids, a for the sesquiterpene moiety is still open to question, but E, E-famesyl cation has been suggested as one possibility and hedycarylol as a second. This moiety is dihydroagarofuran. Therefore, a for the sesquiterpene pyridine alkaloids is nicotinic acid and E, E-famesyl cation and, controversially, hedycaryol. The /3 is amacrocycling ring formation substance (two moieties), from which the alkaloid forms (Figure 62). 

Figure 62. Structural development of sesquiterpene pyridine alkaloids.

Nocotinoyl sesquiterpene alkaloids 109 Non-celastraceous sesquiterpene pyridine alkaloids 110... 

Kuo YH,Chen CH, Kuo LM, King ML, Wu TS, Haruna M, Lee HK. Antitumor agents 112. Emarginatine B, a novel potent cytotoxic sesquiterpene pyridine alkaloid from Maytenus emarginata. J. Nat. Prod. 1990 53 422-428. 

Kuo YH, King ML, Chen CF, Chen HY, Chen CH, Chen K, Lee HK. Two new macrohde sesquiterpene pyridine alkaloids from Maytenus emarginata emarginatine G and the cytotoxic emarginatine F. J. Nat. Prod. 1994 57 262-269. 

Shirota 0,Sekita S, Satake M, Morita H, Takeya K, Itokawa H. Nine regioisomeric and stereoisomeric triterpene dimers from Maytenus chuchuhuasca. Chem. Pharm. Bull. 2004 52 739-746. Shirota O, Sekita S, Satake M, Morita H, Takeya K, Itokawa H. Two new sesquiterpene pyridine alkaloids from Maytenus chuchuhuasca. Heterocycle 2004 63 1891-1896. 

Pyridine was first isolated, like pyrrole, from bone pyrolysates. Its name is derived from the Greek for fire (pyr) and the suffix idine used to designate aromatic bases. Pyridine can also be formed from the breakdown of many natural materials in the environment. Pyridine is used as a solvent, in addition to many other uses including products such as pharmaceuticals, vitamins, food flavorings, paints, dyes, rubber products, adhesives, insecticides, and herbicides. Structurally, pyridine derivatives can range in complexity from the relatively simple monosubstituted pyridine, nicotine (1), to the highly elaborated sesquiterpene pyridine alkaloids, chuchuhuanines [1] (2). 

Members of the Celastraceae family produce a wide variety of macrocyclic sesquiterpene pyridine alkaloids, which will be discussed below. In addition, various nicotinoyl esters of the base sesquiterpene structure p-dihydroagarofuran are produced, such as in the cangorins [160], wilforcidine [161], triptofordinines [162], and related compounds [163]. 

Khat, a drug produced from leaves and shoots of Catha edulis, is used as a stimulant, primarily in East Africa and Southern Arabia [167]. Interest in this drug led to investigation of the components of C. edulis, which included a number of macrocyclic sesquiterpene pyridine alkaloids, the cathedulins. 

In the course of these research programmes, many characteristic bioactive compounds have been reported. Polyester sesquiterpenes and pyridine-sesquiterpene alkaloids with insect antifeedant or insecticidal properties have been isolated from some species and recently sesquiterpene pyridine alkaloids with immunosuppressive or antitumoral activities have also been described. Diterpene triepoxides with potent antileukemic and immunosupressive activities and triterpenoid quinonemethides, named as celastroloids , with antibiotic and cytostatic activities, have been isolated from species of the Celastraceae family. 

These sesquiterpene polyesters are found in a variety of oxygenated forms, being esterified by either aliphatic (acetic, 2-methylbutyric, hydroxyisobutyric, etc.) or aromatic (benzoic, furoic, cinnamic, epoxycinnamic, etc.) acids. Despite their sesquiterpene core, when the ester function is due to nicotinic acid or its derivatives, they are termed sesquiterpene pyridine alkaloids [119]. 

Furukawa M, Makino M, Uchiyama T, Ishimi K, Ichinone Y, Fujimoto Y. Sesquiterpene pyridine alkaloids from Hippocratea excelsa. Phytochemistry 2002 59 (7) 767-77. 

Liao LM, Vieira PC, Rodrigues E, Fernandez JB, da Silva MFGF. Sesquiterpene pyridine alkaloids from Peritassa campestris. Phytochemistry 2001 58(8) 1205-7. 

Liao LM. Sesquiterpene pyridine alkaloids. In Cordell GA, editor. The Alkaloids, Vol. 60. New York Elsevier 2003. p. 287-343. 

Shirota O, Sekita S, Satake M, Morita H, Takeya K, Hokawa H. Two new sesquiterpene pyridine alkaloids from Maytenus chuchuhuasca. Heterocycles 2004 63 (8) 1981. 

Da Yang Y, Yang GZ, Liao MC, Mei ZN. Tliree new sesquiterpene pyridine alkaloids fnan Euonymus fortunei. Helv Chim Acta 2011 94(6) 1139 5. 

Inaba Y, Hasuda T, Hitotsuyangi Y, Aoyagi Y, Fujikawa N, Onozaki A, et al. Abie-tane diterpenoids and a sesquiterpene pyridine alkaloid from Euonymus lutehuensis. J Nat Prod 2013 76(6) 1085-90. 

Zhao ZB, Sun JZ, Mao SC, Guo YW. Fasciospyridine, a novel sesquiterpene pyridine alkaloid from Guangxi sponge Fasciospongia sp. J Asian Nat Prod Res 2013 15 (2) 198-202. 

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