Isoretronecanolic acid

Two further quaternary pyrrolizidine alkaloids have been isolated by Sasaki and Hirata from Anodendron affine Druce. These are anodendrine (26) and its C-1 epimer alloanodendrine. In confirmation of these structures, anodendrine gave (+ )-laburninic acid (27) on palladium-catalysed hydrogenolysis, whereas alloanodendrine gave (-t-)-isoretronecanolic acid, the C-1 epimer of (27). The structures of both zwitterionic alkaloids were then finally established by synthesis. 

The stereochemical interrelationships among all four of the 1-hydroxymethylpyrrolizidines isoretronecanol, lindelofidine, trachelan-thamidine, and labumine, have been determined, insofar as the Cj, Cg relative configurations are concerned, by the chromic acid oxidation studies of Labenskil, Serova, and Men shikov (163). Repeating the oxidation of isoretronecanol originally reported by Adams and Hamlin (63), they were able to isolate two diastereoisomeric l-p3nrrolizidinecarboxylic aci in approximately equal amounts the isoretronecanolic acid of Adams and Hamlin, m.p. 228-229° (dec.) [a] —71.4° (ethanol), (picrate,... 

Anodendrine (17) and alloanodendrine (18) are a pair of zwitterionic alkaloids whose structure was determined by a combination of physical and chemical methods. The synthesis of the former was achieved by treating the methyl ester of labrnninic acid with isopentenyl bromide and hydrolysing the product. The alio base was similarly prepared from (+ )-isoretronecanolic acid (12). 

Isoretronecanol, K22 Isoretronecanolic acid, K22 Isorhoeadine, K1 Isosapogenins, T49 Isoserine, A1 Isosparteines, K21 Isostevane, T35 Isosteviol, T35 Isosylvestrene, T6 Isotenulin, T24 Isothujone, T7 Isothujyl alcohol, T7 Isotirucallol, T51... 

Trachelanthamidinic acid, K22.13 Isoretronecanolic acid, K22.10 Heliotridine, K22.8 Retronecine, K22.6... 

In addition, deoxoprosphylline [36], pipecolic acids, izidines [37], and the bicyclic alkaloids ( )-isoretronecanol, ( )-trachelanthamidine [38] and 6-epi-poranthellidine [39] were synthesized via tandem hydroformyla-... 

It is of interest that 3-methylthiopropenic acid, CH3SCH=CHC02H, has been isolated from two alkaloids, esters of this acid with labumine and isoretronecanol, by Hart et al. (49, 71). 

C. av strale gave two new pyrrolizidene alkaloids cynaustraline, C15H27O4N (amorph. picrolonate, mp 149°) and cynaustine, C15H25O4N (amorph. picrate, mp 135°). Hydrolysis of these bases gave viridifloric acid in both cases and (-f )-isoretronecanol and (-f- )-supinidine, respectively. 

A glycoalkaloid, nervosine, C36H53O12N, was isolated as its picrate (mp 131° [a] -I-12.8° as hydrochloride). Alkaline hydrolysis generated lindelofidine (d-isoretronecanol) and an acid which on hydrolysis with acid generated D-glucose and L-arabinose. The disaccharide obtained on mild hydrolysis was reduced with sodium borohydride and then hydrolyzed further. There was obtained arabinose, indicating that the aldehyde function of the glucose is coupled with the phenolic hydroxyl of the acid moiety. Exhaustive spectral analysis of the latter as well as of its tetrahydro derivative show that nervosine is LXXXIV 132). 

Two alkaloids, lindelofine, C16H27O4N (m.p. 106-107°, [a] +50° picrate, m.p. 123-124° picrolonate, m.p. 134-135°), and lindelofamine, C20H33OBN (m.p. 88°), were obtained from this plant. Alkaline hydrolysis of lindelofine yielded an alkamine, CgHuON (m.p. 40-41°), which was shown to be identical with d-isoretronecanol, and trachelanthic acid. Similarly, alkaline hydrolysis of lindelofamine yielded the same alkamine and a mixture of trachelanthic and tiglic acids. It is suggested that trachelanthic acid is bound to the alkamine and that the tiglic acid esterifies one of the hydroxyls of the former (129). 

---