Synthesis of a Linear Fragment Containing the C23-C26 Stereocenters of Phorboxazole: A Flexible Molecule with Defined Conformation
Document Type
Article
Language
eng
Publication Date
2018
Publisher
Bentham Science
Source Publication
Letters in Organic Chemistry
Source ISSN
1570-1786
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”.
Recommended Citation
Greer, Patrick Bernard and Donaldson, William A., "Synthesis of a Linear Fragment Containing the C23-C26 Stereocenters of Phorboxazole: A Flexible Molecule with Defined Conformation" (2018). Chemistry Faculty Research and Publications. 921.
https://epublications.marquette.edu/chem_fac/921
Comments
Letters in Organic Chemistry, Vol. 15, No. 6 (2018): 472-478. DOI.