119741-01-4Relevant academic research and scientific papers
Pyrrolizidine Alkaloid Analogues. Synthesis of Macrocyclic Diesters of (+/-)-Synthanecine A Containing 12- to 16-Membered Rings
Barbour, Robert H.,Robins, David J.
, p. 1923 - 1928 (2007/10/02)
The first macrocyclic diesters of 2,3-bis(hydroxymethyl)-1-methyl-2,5-dihydropyrrole (2) with ring sizes of 12 to 16 have been prepared.Esterification of the imidazolide (6) of phenyl hydrogen adipate with (+/-)-synthanecine A was achieved at the 6-position.Treatment of the phenyl ester (7) with 1-(trimethylsilyl)imidazole and a catalytic quantity of sodium phenoxide produced the corresponding imidazolide and resulted in silylation of the free hydroxy group to afford the synthanecine A derivative (8).Attempted desilylation of the activated ester (8) followed by lactonisation failed and mixtures of oligomers were probably formed.In the successful route, treatment of (+/-)-synthanecine A (2) with thionyl chloride afforded (+/-)-3-chloromethyl-2-hydroxymethyl-1-methyl-2,5-dihydropyrrolium chloride (3).Nucleophilic displacement of the allylic chloride was carried out with adipic (9a), pimelic (9b), suberic (9c), azelaic (9d), and sebacic (9e) acids in the presence of 1,8-diazabicycloundec-7-ene to yield the 7-monoesters (10a-e) of synthanecine A.Lactonisation of these monoesters was achieved via the pyridine-2-thiol esters to give the new macrocyclic diesters (4c-g) with ring sizes of 12 to 16 in low overall yield (12-16percent).Improved yields (25-30percent) of the dilactones (4c-g) were obtained after rigorous purification and crystallisation of the allylic chloride hydrochloride (3).
