Synlett 2017; 28(09): 1101-1105
DOI: 10.1055/s-0036-1588413
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of the C1–C23 Fragment of the Archazolids and Evidence for V-ATPase but not COX Inhibitory Activity

Gregory W. O’Neil*
a  Department of Chemistry, Western Washington University, Bellingham, WA 98225, USA   Email: oneilg@wwu.edu
,
Alexander M. Craig
a  Department of Chemistry, Western Washington University, Bellingham, WA 98225, USA   Email: oneilg@wwu.edu
,
John R. Williams
a  Department of Chemistry, Western Washington University, Bellingham, WA 98225, USA   Email: oneilg@wwu.edu
,
Jeffrey C. Young
b  Department of Biology, Western Washington University, Bellingham, WA 98225, USA
,
P. Clint Spiegel
a  Department of Chemistry, Western Washington University, Bellingham, WA 98225, USA   Email: oneilg@wwu.edu
› Author Affiliations
Further Information

Publication History

Received: 23 December 2016

Accepted after revision: 17 January 2017

Publication Date:
08 February 2017 (online)


Abstract

A convergent synthesis of a C1–C23 fragment of the archa­zolids has been completed based on a high-yielding Stille coupling to construct the substituted Z,Z,E-conjugated triene. After removal of the protecting groups, the resulting tetrol exhibited evidence for inhibition of the vacuolar-type ATPase (V-ATPase) but not cyclooxygenase (COX) inhibitory activity.

Supporting Information

 
  • References and Notes

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    • Due to short supply, archazolids themselves were not assayed. However, reported V-ATPase inhibitory activity of concanamycin A and archazolid A are similar. The IC50 values for concanamycin A and archazolid A of purified M. sexta holoenzyme were reported as 0.8 nmol/mg V-ATPase and 0.5 nmol/mg V-ATPase, respectively. Archazolid:
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    • Concanamycin:
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