Synthetic studies towards the pectenotoxins: a review

Abstract

In this article we provide an overview of synthetic studies towards pectenotoxins (PTXs) that have been reported by several research groups. The difficulties encountered in the synthesis of these series of polyketides are highlighted by the fact that only one total synthesis of PTX4 and PTX8 has been completed to date. The strategies used in the critical bond forming steps and the introduction of key stereogenic centres are compared and contrasted.

A Structural Basis for Regulation of Actin Polymerization by Pectenotoxins

“…Metabolism of PTX-2 to other PTX derivatives by shellfish, and biosynthesis of analogues in algae, has provided a growing library of compounds [1][2][3][4]8,9,12,17 whose cytotoxicity continues to be evaluated for potential therapeutic utility. 15 At a molecular level, this library of chemical modifications can help probe the versatility of the PTX-binding surface on actin, providing vital information toward the design of novel analogues with improved pharmacological profiles.…”

“…15,16 To date, 14 PTXs have been isolated and characterized (see Figure 1(a) for selected examples). 1,17 Their common structural features include a spiroketal group, three oxolanes, a bicyclic ketal, and a six-membered cyclic hemiketal. The main differences between these compounds involve the stereochemistry of the spiroketal group and the level of oxidation at C18, C32, C34 and C38.…”

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

“…Unfortunately, the C31–C40 region of the pectenotoxin structure that contains the GH-bicyclic heterocycle has proven to be quite challenging to prepare, requiring longest linear sequences of ∼21 to >30 chemical steps to establish only 10 backbone carbons. 9 …”

Interplay of Cascade Oxidative Cyclization and Hydride Shifts in the Synthesis of the ABC Spiroketal Ring System of Pectenotoxin‐4

“…[2] The exquisite architectural complexity of these 26-membered macrolactones, which consist of either 19 or 20 stereogenic centers embedded within three tetrahydrofuran rings, plus one spiroketal and one bicyclic ketal, poses a synthetic challenge that has attracted considerable attention from many research groups. While significant synthetic endeavors have been directed toward the pectenotoxins, [3] to date only one total synthesis of PTX-4 and PTX-8 has been reported. [4] In particular we were drawn to the C1-16 fragment of the pectenotoxins, because it contains a pair of THF rings terminating with a spiroketal unit that could be derived from a linear precursor; a synthesis would allow us to develop two concepts that should find general use in organic synthesis.…”