778
to afford the trihydroxydienynes 5 or 6. Careful catalytic hydrogenation of triols 5 or 6 in MeOH, in the
presence of Lindlar catalyst and quinoline poison, generated previtamins 3 or 4.16
Scheme 4. a: Pd(PPh3)2(OAc)2-CuI, Et2NH, DMF. b: TBAF, THF (85%, two steps). c: Lindlar, quinoline, H2, MeOH (70%)
In summary, we have developed an efficient synthesis of A-ring precursors 8 and 9 from inexpensive
(−)-quinic acid. Key features of these approaches are the selective deprotection of a silyl ether derivative
and the excellent yield of the Mitsunobu reaction, which takes place with total inversion of configuration.
Coupling of these synthons with the appropriate CD-rings/side chain fragment provides access to the
important 6-s-cis locked analogues 3 and 4. Synthesis of other possible previtamin stereoisomers is now
in progress in our laboratory.
Acknowledgements
Financial support from Comisión Interministerial de Ciencia y Tecnología (Spain; Project BIO98-
0770) and Fundación Príncipe de Asturias (Dr. Severo Ochoa Award to M.F.) is gratefully acknowledged.
We also thank the Ministerio de Educación y Cultura (Spain) for postdoctoral fellowships (S.F. and M.F.)
and Solvay-Duphar (Wesp, Holland) for the generous gift of vitamin D3 which was used for preparation
of Grundmann’s ketone.
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