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Total synthesis of veratrum alkaloids

University of British Columbia

The initial work toward the construction of the basic skeleton of verticine (88) and related Veratrum alkaloids is described. Hecogenin (acetate) (115) was converted by a known method to rockogenin 12-methanesulfonate 3-pivalate (118), which gave in excellent yield 3β-pivaloyloxy-C-nor-D-homo-(25R)-5α,12α-spirst-13(18)-en (119b). Hydroboration of the 13(18) double bond is discussed with respect to the stereochemistry of the major product, namely 13β-hydroxymethyl-C-nor-D-homo-18-nor-(25R)-5α,12α -spirstan-3β-ol (121). The configuration at C-13 of (121) was reversed by means of epimerization of the aldehyde intermediate (148). 3β-Acetoxy-13α-acetoxymethyl-C-nor-D-homo-18-nor-5α,12α-spirostan (153) was prepared from (148) and the performic acid degradation of the spiroketal side chain was investigated The C₂₁ pregnajervane ketone, namely 3β-acetoxy-13α-acetoxymethyl-18-nor-12α-pregnajervan-20-one (196) was obtained from the diacetate (153) with considerable difficulty. The difficulty was chiefly associated with selective hydrolysis of the performic acid oxidation product. Finally the ketone (196) was coupled with 2-lithio-5-methylpyridine. The coupling product was characterized after acetylation by n.m.r. and mass spectroscopy as 3β,18-diacetoxy-20-hydroxy-22,23,24,25,26-N-hexadehydro-5α,13β(H) , 17α(H)-veratranine (201).

Text

2011-03-10

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http://hdl.handle.net/2429/32309

Chemistry

University of British Columbia

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