Alkaloids actinidine

Stereocontrolled syntheses of the natural iridolactone, (-l-)-iridomyrmecine 207 (Eq. 21) and the alkaloid (-)-actinidine 213 (Scheme 24) have been accomplished based on an ISOC reaction as the key step [56,57]. ISOC reaction of 204... 

Birds Taiwan stick insect Monoterpenoid alkaloid actinidine Chow and Lin,... 

A synthesis of the monoterpene alkaloid ( )-actinidine has been accomplished through the intramolecular cycloaddition of a substituted pyrimidine (81JCS(P1)1909). Condensation of the diester (756) with formamidine provided the pyrimidine precursor (757) which when heated at its melting point (203 °C) underwent cycloaddition with elimination of isocyanic acid to produce the pyridone (758). Conversion of the pyridone into the chloropyridine was effected with phosphoryl chloride. The chlorine atom was then removed by hydrogenoly-sis over palladium on charcoal to afford the racemic alkaloid (759 Scheme 175). 

The Valeriana alkaloid actinidin (32) is also derived from a cyclopentanoid monoterpenoid and was further metabolized into an unknown alkaloid. 

Sammes and his group (77JCS(P1)663 78JCS(P1)1293 81JCS(P1)1909) attempted the thermal intramolecular cycloaddition of the substituted pyrimidine 507 possessing an alkyne to produce a monoterpene alkaloid ( )-actinidine (511)(Scheme 64). Upon thermolysis of the pyrimidine 507 at 200°C in a sealed tube, using dimethylformamide as solvent, intramolecular cycloaddition led to the known pyridone 509 in 87% yield by the loss of the amide bridge from intermediate 508. Conversion of the pyridone 509 into the chloropyridine followed by reductive dechlorination afforded racemic actinidine 511. 

Generally iridoids are divided in two categories, iridoids and secoiridoids and these mostly exist as glycosides. Iridoids are also found in aldehydes, alcohols (iridodial (1) iridodiol (2)), alcoholic esters (valepotriates), lactones (irridomyrmecin (3), nepetalactone (4)) and alkaloids (actinidine (5), skytanthine (6)) forms. Secoiridoids on the other hand are formed by cleavage of cyclopentane ring of iridoid. 

Refreshing synthetic work in the monoterpenoid alkaloid area has appeared during the past year. The pyridine derivative (78), an isomer of the alkaloid actinidine (79) and as yet unknown in nature, has been synthesized (Scheme 6). ... 

The sesquiterpenes present in valerian include isovaleric acid, valerenic acid, valerenal, valeranone, and valerenol. The alkaloids found in valerian include valeranine and actinidine. 

Natural (—)-actinidine (9a) is prepared from nepetalinic acid imide (262) via dichloropyridine (263) 403) and from iridodial (264) via bis (2,4-dinitrophe-nyl)hydrazone 404) or treatment with ferric ammonium sulfate (Scheme 19) 405). (+)-Actinidine (9b), the enantiomer of natural alkaloid, is synthesized from acid chloride 265, derived from (+)-pulegone, via vinylketone 267 (Scheme 20) 406). Racemic actinidine (9) is prepared by intramolecular cycloaddition of an acetylene across a pyrimidine ring in 5-(hept-5-yn-2-yl)-4,6-dihydroxypyrimidine (268) followed by chlorination and hydrogenation (Scheme 21) 407). 

The (+)-enantiomer (40) of actinidine, an alkaloid of Valeriana officinalis and Actinidia polygama, has been synthesized as outlined in Scheme 7, the starting material being obtained from (+)-pulegone.35... 

There is a small group of alkaloids related to the iridane monoterpenes which have the general structure (86). The synthesis of a new representative, valerianine (86 R = OMe), found in Valeriana officinalis L., has been described (Scheme 2), and an isomer (87) of the known actinidine (86 R = H) has been made from citronellonitrile (88) (Scheme 3). Thin-layer chromatography of V. officinalis extracts shows 12 zones whose constituents react with DragendorfTs reagent. ... 

Actinidine (92), a plant alkaloid (see section 8), is also a minor component of the defence secretion of the Australian cock-tail ant Iridomyrmex nitidceps (G.W.K. Cavill et al.. Tetrahedron, 1982, 38, 1931), a fact which indicates that ants may obtain toxins (or at least their precursors) from dietary sources. Actinidine has been synthesised (M. Nitta, A. Sekiguchi and H. Koba, Chem.Letters, 1981, 933). Anabaseine (118), a dihydro derivative of anabasine a well known tobacco alkaloid, is present in the poison glands of Aphaenogaster ants for which it also an attractant (J.W. Wheeler et al.. Science, 1981, 211, 1051). Ants from Puerto Rico produce the simple tetrahydropyridine (119) (T.H. Jones, M.S. Blum and... 

Actinidine (91) is produced by several insects. It was found to be a component of the ants Iridomyrmex discors [267], and I. purpureus [268], Pygidial gland secretions of the ant Tapinoma melanocephalum contained 91, and the alkaloid was repellent to worker ants of this species [269], Actinidine was identified in a defensive secretion of the stick insect Megacrania alpheus [270], and it was present in trace amounts in the defensive secretion of rove beetles [271] and leaf beetles [272]. Ventral glands of Nematus sawfly larvae also contained low levels of 91 [273],... 

Only a few examples for alkaloids of terpenoid origin have been identified from arthropods. The ant Mommorium fiddi was shown to contain (2 ) and (2 2)-farnesylamine (148), which, surprisingly, constitutes the first identification of farnesylamine or any ofits derivatives in nature. The defensive agent actinidine (16) has been found in a number of insect species and probably derives from an iridoid precursor, although the details of actinidine biosynthesis in insects have not yet been fully clarified." ... 

Chromatography of the tertiary base fraction of the roots of Valeriana officinalis gave an optically active alkaloid ([a]D -10.5°) having a molecular formula CnH15NO (75). The proton NMR spectrum indicated a pyridine derivative unsubstituted at C-2 and C-6, together with the presence of a doublet methyl (1.32 ppm), a methoxy group (3.40 ppm), and a benzylic methylene (4.46 ppm). In this way, the structure of valerianine was proposed as 13, in which the S stereochemistry at C-8 was deduced through relationship with actinidine (14) and tecostidine (15) (75). 

The bark of Tecoma arequipensis (Bignoniaceae) yielded a major alkaloid, (-)-S-A-nor-methylskytanthine (32), [a]D -21.5°, whose structure was established through X-ray crystallographic analysis of the N-(4-bromophenylthiourea) derivative (36). Other alkaloids detected by GC-MS analysis included 5,6-dehydroskytanthine, skytanthine, actinidine, 5-hydroxy-skytanthine and tecomanine. Additional components were partially characterized (MS data only) as two hydroxytecomanines and four... 

In addition, to actinidine (14), Janot and co-workers also isolated a new monoterpene alkaloid from the roots of Valeriana officinalis following treatment with ammonia (25). The isolate was analyzed for the formula Ci0H8N2O, and the UV spectrum showed maxima at 261,314, and 324 nm, and the IR spectrum a band at 1680 cm-1 for an aryl ketone. The mass spectrum displayed a molecular ion at m/z 172 with fragment ions at m/z 157 (M+-15) and 129 (MM3), suggesting the presence of a methyl ketone. A methyl singlet was observed at 2.65 ppm, and a complex pattern of five... 

Two quaternary alkaloids, derivatives of actinidine and 8-hydroxyactini-dine, previously isolated from Valeriana officinalis (1), A-(4-hydroxyphe-nethyl)-actinidine (130) and 6,7-dihydro-4-(hydroxymethyl)-2-(4-hydroxy-phenethyl)-7-methyl-5//-2-pyridinium (124), were isolated from Valeriana wallichii (132). 

Two alkaloids were isolated from the aerial parts of Spigelia anthelmia (Loganiaceae) by Wagner and co-workers, one of which was isoquinoline and the second of which was partially characterized as being isomeric with actinidine. A series of choline derivatives was isolated from the aqueous extract. Preliminary biological evaluation indicated that the alkaloids are involved with the cardiotonic activity reported for the plant (246). 

The C9 monoterpenoid alkaloid jasminidine (126) has been isolated from Syringa vulgaris. (+)-Actinidine (127) is obtained by hydroxylamine treatment... 

In the subterranean parts of V. officinalis, a number of alkaloids (0.05-0.1%) occur actinidine, 8-methoxyactinidine (valerianine) and naphthyridylmethylketone have been found as well as several other, yet unidentified alkaloids. Furthermore, isoferulic acid, y- aminobutyric acid, free fatty acids and short-chain carboxylic acids have been isolated. In the leaves of V officinalis, the presence of four flavonoids has also been demonstrated. From the subterranean parts of V. jatamansi, isomers of lanarin isovalerate and 4-methoxy-8-pentyl-l- naphtholic acid were isolated and characterized [50, 51]. 

A quaternary alkaloid isolated (202) from the roots of Valeriana officinalis L. as the chloride, C18H22NOCI (mp 201°-203° decomp. [ ]o +50.5° in methanol) has been shown to be A-jS-(p-hydroxyphenyl)-ethylactinidinium chloride (CLXI). Pyrolysis of CLXI gives -actinidine (CLX) hydrochloride and, according to mass spectral evidence, p-hydroxystyrene. 

---