Actinidine monoterpene alkaloids

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). 

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. 

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... 

This photoreductive cyclization is of great synthetic utility as illustrated below in the synthesis of actinidine and isooxyskytanthine, two rare monoterpenic alkaloids which... 

Nakamura M, Kido K, Kinjo J, Nohara T (2000) Two novel actinidine-type monoterpene alkaloids from Incarvillea delavayi. Chem Pharm Bull 48 1826-1827... 

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. ... 

A number of important alkaloids are derived from monoterpenes. Monoterpenoid alkaloids are comparably simple compounds formed by addition of nitrogen atom to an existing monoterpene, mainly of the secologanin type. Several monoterpenoid alkaloids have been isolated and characterized and classified based upon their structural characteristics. The more common and pharmaceutically important types such as actinidine, skytanthine, and gentianine are discussed herein. 

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