A Scalable Stereoselective Synthesis of Scymnol
Raju Adhikari A , Darren J. Cundy A , Craig L. Francis A B , Mariana Gebara-Coghlan A , Beata Krywult A , Carolyn Lubin A , Gregory W. Simpson A and Qi Yang AA CSIRO Molecular Science, Bag 10, Clayton South VIC 3169, Australia.
B Corresponding author. Email: craig.francis@csiro.au
Australian Journal of Chemistry 58(1) 34-38 https://doi.org/10.1071/CH04175
Submitted: 16 July 2004 Accepted: 5 October 2004 Published: 14 January 2005
Abstract
A high-yielding, stereoselective synthesis of scymnol 1 has been carried out in five steps starting from commercially available cholic acid 2. The synthesis was designed with the aim of eventual large-scale processing. Triformyloxycholic acid chloride 4 was treated with the magnesium enolate of diethyl malonate to afford the β-keto diester, diethyl 3α,7α,12α-triformyloxy-24-oxo-5β-cholestane-26,27-dioate 5. The key step in the synthesis was the stereoselective hydrogenation of β-keto diester 5 to give the corresponding β-hydroxy diester 6 using a BINAP ruthenium(ii) catalyst. Subsequent reduction of the diester moiety and deprotection of the hydroxyl groups afforded scymnol 1.
Acknowledgments
The authors acknowledge the financial support of McFarlane Marketing (Australia) Pty Ltd and the excellent technical assistance of Noel Hart, Ahmed Tawfik, Mike Falkiner, and Stuart Littler.
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