Keywords Heterocyclization • Medium-ring ethers • Natural products • Oxacycles •
Synthesis
1 Introduction
Medium-sized cyclic ethers have attracted much attention from synthetic and
medicinal chemists due to their presence in a wide range of biologically active
natural products, including marine ladder toxins (brevetoxins, ciguatoxins, etc.),
lauroxanes, and heliannuol A, along with members of the eunicellin family, or
antibiotics [1]. Examples of their occurrence in Nature include isolaurepinnacin,
laurencin, obtusenyne, brevetoxin, and many others (Fig. 1). In view of the increasing number of biologically active natural products containing medium- and largesized cyclic ether derivatives, much attention has been focused on efficient
approaches towards these systems. However, the preparation of these skeletons is
generally difficult by standard cyclization methods [2] and remains a significant
challenge, primarily because both entropic (probability of the chain ends meeting)
and enthalpic (increasing strain in the transition state) barriers hamper cyclization
strategies [3]. Nevertheless, the challenge in their efficient construction has led to
Fig. 1 Representative examples of medium-sized ethers
322
E. Soriano and J. Marco-Contelles
Synthesis
1 Introduction
Medium-sized cyclic ethers have attracted much attention from synthetic and
medicinal chemists due to their presence in a wide range of biologically active
natural products, including marine ladder toxins (brevetoxins, ciguatoxins, etc.),
lauroxanes, and heliannuol A, along with members of the eunicellin family, or
antibiotics [1]. Examples of their occurrence in Nature include isolaurepinnacin,
laurencin, obtusenyne, brevetoxin, and many others (Fig. 1). In view of the increasing number of biologically active natural products containing medium- and largesized cyclic ether derivatives, much attention has been focused on efficient
approaches towards these systems. However, the preparation of these skeletons is
generally difficult by standard cyclization methods [2] and remains a significant
challenge, primarily because both entropic (probability of the chain ends meeting)
and enthalpic (increasing strain in the transition state) barriers hamper cyclization
strategies [3]. Nevertheless, the challenge in their efficient construction has led to
Fig. 1 Representative examples of medium-sized ethers
322
E. Soriano and J. Marco-Contelles