Open Collections

Total synthesis of (+)-8-isocyano-10-cycloamphilectene

University of British Columbia

A 36-step synthesis of the tetracyclic diterpene (+)-8-isocyano-10-cycloamphilectene (11) from (R)-pulegone (40) is described. An efficient four-step process gave 38 from 40 with complete regioselectivity in the introduction of the carbon-carbon double bond. Methoxycarbonylation and reduction were followed by stereocontrolled alkylation and produced 16. Treatment of the enol trifluoromethanesulfonate derived from 16 under conditions (Pd(PPh₃)₄, LiCl, THF, reflux) appropriate for an intramolecular Stille-type coupling gave the bicyclic compound 18. A highly face- and regioselective Diels—Alder cycloaddition process gave the tricyclic compound 54. The bromine atom in 54 was reductively removed in a samarium(II) induced protiodebromination process, and three further synthetic steps gave compound 21. At this point, the configurations at four of the seven stereocentres had been set and attention was turned towards the introduction of the fourth required carbocyclic ring. Allylic oxidation, reduction of the carbon-carbon double bond by catalytic hydrogenation and a two-step methoxycarbonylation process gave the intermediate 65 which was transformed into 32 by an efficient five-step synthetic sequence in which the introduction of C-7 of the cycloamphilectane skeleton was an important step. An aldol condensation reaction followed by a chemoselective reduction gave compound 30 which was subjected to an alkylation, epimerization, alkylation sequence wherein the gem-dimethyl function was installed yielding the ketone 81. At this point, the complete carbon skeleton with the correct configuration at each stereogenic centre for the natural product was in hand. Deoxygenation and degradation of the ester function to an isocyanide group completed the synthesis of 11. [Molecular structures]

Thesis/Dissertation

application/pdf

2009-06-02

For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.

http://hdl.handle.net/2429/8588

Chemistry

University of British Columbia

UBCV

DSpace