Actinidine, synthesis

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). 

A new synthesis of ( )-actinidine has been reported it is interesting in that it has, as its key step, the thermal intramolecular cycloaddition of an acetylenic pyrimidine.34 A further synthesis of ( )-muscopyridine, based on a regioselective cyclopentenone annulation, has been described.35... 

Scheme 74) [330], The use of photoreductive cyclization for the total synthesis of actinidine and isooxyskytanthine has been reported [331],... 

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. ... 

Using functionalized 3,4-dialkyl pyridines, Shiao and co-workers have described an alternative synthesis of actinidine (183) based on mixed metal reactions with l-(alkoxycarbonyl)pyridinium salts. Thus, ethyl 3-iodopropi-onate was successively treated with zinc and cuprous cyanide, and after being cooled to —78°C the resulting solution was reacted with 5-methyl-methylnicotinoate (158) and the mixture warmed to room temperature to afford 159. Cyclization and decarboxylation was effected with sodium hydride followed by heating in aqueous solution to afford 160. A Wittig reaction on 160 gave the olefin 161, and catalytic hydrogenation (Pd-C) afforded ( )-actinidine (134) (Scheme 5) (183). 

A new synthesis of ( )-actinidine (134) has been described by Jones and Escudero-Hemandez using a pyridine radical cyclization as the... 

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

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