Synthese der Phoracantholide K, O und M

Article abstract of DOI:10.1002/hlca.19800630821

Two 14membered ring lactones 3 and 4 and a 12membered ring lactone 5 isolated from the metasternal secretion of the eucalypt longicorn Phoracantha synonyma have been synthesized as racemic mixtures by the following method.Reaction of the dilithium derivative of 5-hexynoic acid (6) with threo-8-bromo-2,4-isopropylidenedioxyoctane (7), followed by removal of protecting group and esterification with diazomethane gave methyl-threo-11,13-dihydroxy-5-tetradecynoate (8) (s.Scheme 2).Partial hydrogenation of the triple bond in 8 with Lindlar Pd-catalyst, followed by saponification lead to (threo,Z)-11,13-dihydroxy-5-tetradecenoic acid (10).The dihydroxy acid 10 was converted into the S-(2pyridyl) thioate and cyclized in diluted benzene solution under the influence of silver ions to yield the corresponding 12- and 14-membered lactones in approximately equal amounts.Isomerization of the mixture with p-toluenesulfonic acid in methylene chloride yielded the 14-membered lactone (cis-11,13-5Z)-11-hydroxy-5-tetradecen-13-olide almost excusively.It proved to be identical in its properties with natural phoracantholide K (3).With 5-hexynoic acid and 7-tetrahydropyranyloxy-octyl bromide or 5-tetrahydropyranyloxy-hexyl bromide as starting materials (+/-)-phoracantholide O (4) and M (5) have been synthesized in an analogous manner.