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Letters in Organic Chemistry


ISSN (Print): 1570-1786
ISSN (Online): 1875-6255

Research Article

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

Author(s): Patrick B. Greer and William A. Donaldson*

Volume 15 , Issue 6 , 2018

Page: [472 - 478] Pages: 7

DOI: 10.2174/1570178614666170710102015

Price: $65


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.

Graphical Abstract

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