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Synthesis of a Linear Fragment Containing the C23-C26 Stereocenters of Phorboxazole: A Flexible Molecule with Defined Conformation

[ Vol. 15 , Issue. 6 ]

Author(s):

Patrick B. Greer and William A. Donaldson*   Pages 472 - 478 ( 7 )

Abstract:


Background: Phorboxazole is a polycyclic natural product which exhibits antitumor activity. The synthesis of C20-C26 segment of phorboxazoles, possessing 5 contiguous stereocenters, is described.

Methods: A double diastereoselective aldol reaction using an Evans chiral oxazolidinone with a chiral aldehyde generates the C23-C25 stereocenters. Chain extension via Horner-Wadsworth-Emmons olefination and subsequent functional group manipulation set the stage for introduction of C26 stereocenter via a Sharpless asymmetric dihydroxylation. A Roskamp homologation serves to introduce C20-C21 carbons.

Results: The acyclic segment was generated in 13 steps, 7.6% overall yield was obtained from the precursors 4 and 5. Examination of the 3JH-H coupling constants for several of the compounds revealed that they exist in predominantly one conformer.

Conclusion: The linear molecules 13, 17, and 18 serve as additional examples of acyclic molecules with defined conformation. The defined conformations of these molecules are due to the presence of a bulky “inductor group”.

Keywords:

Asymmetric synthesis, dihydroxylation, conformational analysis, linear fragment, molecule, stereocenters.

Affiliation:

Department of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881, Department of Chemistry, Marquette University, P. O. Box 1881, Milwaukee, WI 53201-1881

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