Synthetic studies towards stemofoline

Coates, Helen Margaret (1989) Synthetic studies towards stemofoline. University of Southampton, Doctoral Thesis.

Abstract

Synthetic studies towards the alkaloid stemofoline have been carried out. For the initial approach the key reaction in the proposed synthetic scheme was a Diels-Alder reaction between Danishefsky's diene and a substituted imine. Thus, reaction of 1-methoxy-3-trimethylsilyloxybutadiene and N-[3-methyl-2-trimethylsilylmethyl-prop-2-enylidene]benzylamine (190) provided N-benzyl-2-[2-(1-methyl-3-trimethylsilyl)propenyl]-2,3-dihydropyridin-4-one (180). The intramolecular 1,4-conjugate addition of the allyl silane moiety in (180) to the enaminone functionality has been explored. Preparation of the bicyclic intermediate was achieved by photocyclisation of the corresponding iminium perchlorate salt. Thus, irradiation of N-benzyl-4-methoxy-2-[2-(1-methyl-3-trimethylsilyl)propenyl]2,3-dihydropyridinium perchlorate (203) gave 8-benzyl-7-methyl-6-methylene-8-azabicyclo[3.2.1]oct-3-ene (205). In an alternative approach, bicyclic intermediates were prepared by the 1,3-dipolar cycloaddition of pyridinium betaines with various dipolarophiles. Specifically, reaction of 4-methoxybenzyl-3-oxide-pyridinium and phenyl vinyl sulphone gave a good yield of 8-(4-methoxybenzyl)-6-phenylsulphonyl-8-azabicyclo[3.2.1]oct-3-en-2-one (307) with protected amine and ketone functionalities. It has been demonstrated that debenzylation of (307) can be effected by oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone to give 6-phenylsulphonyl-8-azabicyclo[3.2.1]oct-3-en-2-one (280). Further, in model studies, the unmasking of the ketone was achieved by oxidative desulphonylation using oxodiperoxymolybdenum (pyridine)-hexamethylphosphoramide.

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