Synthesis of 12-Methyl-1, 2, 3, 4, 6, 7, 12, 12b-octahydro-2, 6-methanoindolo[2, 3-a]quinokizine

Abstract

12-Methyl-l,2,3,4,6,7,12,12b-octahydro-2,6-methanoindolo[2,3-a]quino-lizine (I), which represents the fundamental skeleton of sarpagine type indole alkaloids, was synthesized. Thus methyl ester (XI) hydro-chloride of N-benzyl-1-methyltryptophan was treated with methyl 3-formylpropionate to form tetrahydro-[beta]-carboline derivative (XV), from which 6,10-imino-5H-cyclooct[b]indole derivative (XVTI) was prepared by Dieckmann cyclization with sodium hydride under a certain working condition. This was condensed with methyl bromoacetate followed by ketone fission to yield ketoester (XX), from which N-benzyl group was reductively removed and then converted to N-methyl derivative (XXIII). The ethylene thioketal (XXV) of the latter was desulfurized as usual and the product was reduced by lithium aluminum hydride to furnish the corresponding alcohol (XXVII), which was tosylated with tosyl chloride in pyridlne in the cold. Spontaneous quaternization of the tosylate took place forming the cyclized quaternary base (XXVIII), the chloride salt of which was submitted to pyrolysis reaction to produce the desired base (I).