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. 2017 Oct 6;19(19):5154-5157.
doi: 10.1021/acs.orglett.7b02435. Epub 2017 Sep 13.

Function-Oriented Studies Targeting Pectenotoxin 2: Synthesis of the GH-Ring System and a Structurally Simplified Macrolactone

Natasha F O'Rourke  1 , Mu A  2 , Henry N Higgs  2 , Alan Eastman  2 , Glenn C Micalizio  1
Affiliations

Function-Oriented Studies Targeting Pectenotoxin 2: Synthesis of the GH-Ring System and a Structurally Simplified Macrolactone

Natasha F O'Rourke et al. Org Lett. .

Abstract

A chemical foundation for function-oriented studies of pectenotoxin 2 (PTX2) is described. A synthesis of the bicyclic GH-system, and the design and synthesis of a PTX2-analogue, is presented. While maintaining critical features for actin binding, and lacking the Achilles' heel for the natural product's anticancer activity (the AB-spiroketal), this first-generation analogue did not possess the anticancer properties of PTX2, an observation that indicates the molecular significance of features present in the natural product's CDEF-tetracycle.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
Introduction to the pectenotoxins.
Figure 2
Figure 2
Structure of PTX2 bound to actin.
Figure 3
Figure 3
Retrosynthetic strategy for the C30–C40 subunit.
Figure 4
Figure 4
Synthesis of the GH-bicyclic domain of the pectenotoxins from the crotylation product of furfuraldehyde.
Figure 5
Figure 5
In silico docking experiments for design of a first-generation PTX2-inspired agent.
Figure 6
Figure 6
Establishment of a synthesis pathway capable of fueling function-oriented studies: convergent assembly of a PTX2-inspired agent.
See this image and copyright information in PMC

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