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The total synthesis of veratrum alkaloids

University of British Columbia

The condensation of a C-nor-D-homo steroidal portion with the lithium derivative of various substituted pyridines is outlined as a general method for the synthesis of Veratrun alkaloids. The application of this approach to the synthesis of verticine (138), a representative of the a-cevanine bases is described. Hecogenin acetate (180) was converted in excellent yield to 33-acetoxy-13a-acetoxymethyl~18-nor-5a,12a-spirostan (240). Performic acid degradation of the spiroketal side chain in 240 gave 38-acetoxy-13et-acetox.ymethyl-18-nor-12a-pregnajervan-20-one (260). This ketone was coupled with 2-lithio-5-methyl pyridine to give after acetylation 33,18-diacetoxy-20-hydroxy-20,23,24,25,26-N-hexadehydro-5a,136(H),17a(H)-vcratraiiine (277). The coupling product vras reduced with PtC^ in acetic acid to 33,18-diacetoxy-5ct,133(H),17a(H)-veratranine (287). The final conversion to the hexacyclic a-cevane skeleton (90) was attempted by heating 287 at 130° for 72 hours in triglyme. The above results open the possibility of the synthesis of several hypotensive Veratrum alkaloids and the access to several compounds not easily obtained from the natural products by degradation reactions. While some of the naturally occurring alkaloids are known to exhibit hypotensive activity, it is not known whether alterations in stereochemistry and structure will cause enhancement or loss of such activity.

Text

2010-01-22

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http://hdl.handle.net/2429/19070

Chemistry

University of British Columbia

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