Retronecine

Trichodesmine, CigHa70gN, m.p. 160-1° (dec.), [ ]d+ 38° (EtOH), gives a methiodide, m.p. 202° (dec.), and on alkaline hydrolysis yields retronecine (p. 607) and dZ-lactic acid with isobutyl methyl ketone, the latter probably arising from a -ketonic acid first formed. ... 

In view of the identity, so proved, of l-methyl-7-ketopyrrolizidiiie (IX) with retronecanone, it follows that the carbonyl group in the latter must be at C , and that this must also be the position of the secondary carbinol group in retronecine (IV), retronecanol (VIII), deoxyretronecine (XII) and platynecine (V), and also in heliotridine and hydroxyheliotridane, which Adams regards as stereoisomers of retronecine and retronecanol respectively. 

Monocrotaline on alkaline hydrolysis yields retronecine and monocrotic acid, CjHijOg, b.p. 145-6°/18 mm., [a]p 0°, which forms a p-bromo-phenacylester, m.p. 78°,and a methyl ester, b.p. 94-6°/18 mm., characterised by a 2 4-dinitrophenylhydrazone, m.p. 95-6° see below). The acid gives the iodoform reaction and is oxidised by sodium hypobromite to a mixture of dl- and mcso-aa -dimethylsuccinic acids (I). These and other reactions show that monocrotic acid is a -dimethyllaevulic acid (II) and this has been eonfirmed by comparison with a synthetic specimen of the acid. The methyl ester of the synthetie acid forms a mixture of 2 4-dinitrophenylhydrazones, m.p. 108-9° and 121-2°, into which the analogous produet, m.p. 95-6°, first made from methyl monocrotate see above), has also been separated. 

On the evidence available there is no reason to doubt that the necyl-necines or parent alkaloids of this group are constituted normally, in which case (VI p. 613) probably represents a typical retronecine ester. 

A further example is given in reference [88] Selective esterification of retronecine, the dialcoholic component of a pyrolizidine alkaloid, by the imidazolide method was found to be superior to the acid chloride/pyridine method. Acylation of the 9-position of retronecine with tiglic acid, pivalic acid, isobutyric acid, and propionic acid was investigated concerning the steric requirement of the carboxylic acid. 

Figure 2.11 Pyrrolizidine alkaloid toxins including (a) the pyrrolizidine nucleus, (b) retronecine, a less toxic monoester, and (c) jacobine, a highly toxic cyclic diester.

Cbz-4-hydroxy-L-proline was used in the preparation of 72 (the Geissman-Waiss lactone), which is a synthon for necines (82H23). This compound was prepared in eight steps (62JOC139). The alkaloids retronecine, platy-necine, and croalbinecine were prepared from the lactone (83H1331). 

We have extended our work on a new synthesis of the antiprotozoal antibiotic anisomycin to the necine bases of the pyrrolizidine alkaloids, in particular retronecine and crotanecine. The key intermediate, (2R,3S,4R)-2-(alkoxy-carbonylmethyl)-3,4—isopropylidenedioxypyrrolidine, has been prepared by three distinct routes from D-ribose and g-erythrose, using reactions of high stereoselectivity. 

The Geissman-Waiss lactone (7)( ) is a well-known precursor of (+)- retronecine ( ) ( -y-), one of the most common necine bases... 

Delair and colleagues found that an asymmetric pyrrolidone 344 might serve as a common precursor of (+)-Retronecine 345 and (+)-Amphorogynine A and D (equation 132). The ring expansion was a key and efficient step during the synthetic process and was performed with Tamura s Beckmann reagent. 

Pyrrohzidine alkaloids Pyrrohzidine Acetyl- lycopsamine Acetyl-intermedine Europine Homospermidine namine Indicine-A-oxide Meteloidine Retronecine... 

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