Maitotoxin: An Inspiration for Synthesis

Abstract

Maitotoxin holds a special place in the annals of natural products chemistry as the largest and most toxic secondary metabolite known to date. Its fascinating, ladder-like, polyether molecular structure and diverse spectrum of biological activities elicited keen interest from chemists and biologists who recognized its uniqueness and potential as a probe and inspiration for research in chemistry and biology. Synthetic studies in the area benefited from methodologies and strategies that were developed as part of chemical synthesis programs directed toward the total synthesis of some of the less complex members of the polyether marine biotoxin class, of which maitotoxin is the flagship. This account focuses on progress made in the authors’ laboratories in the synthesis of large maitotoxin domains with emphasis on methodology development, strategy design, and structural comparisons of the synthesized molecules with the corresponding regions of the natural product. The article concludes with an overview of maitotoxin’s biological profile and future perspectives.

Are there limits to rational chemical synthesis?

“…此外, 他还 设计了一辆纳米小车 [70] (图4). Maitotoxin [72] 和 Aconitine [73] [74,75] Chemical synthesis is the purposeful execution of one or more reactions to obtain a product, or several products, which could modify the existing molecular frameworks, or make a complex (often natural) molecule from simple reagents. There are several possible reasons to make complex molecules by total chemical synthesis.…”

Organic synthesis: the art and science of replicating the molecules of living nature and creating others like them in the laboratory

“…Its applications have been equally impressive and continue to expand into new domains, thereby increasing its impact on science and society. Thus, from the tiny molecule of urea (CH 4 N 2 O, see figure 6) containing a single carbon atom and no stereogenic site, synthetic organic chemists of our time dare to attempt the synthesis of giant molecules such as that of maitotoxin (C 164 H 256 O 68 S 2 Na 2 , see figure 6), the largest secondary metabolite discovered thus far from nature, boasting 164 carbon atoms and 99 sites of stereoisomerism [40]. And from dyes and pharmaceuticals, organic synthesis came to provide the foundation of a whole new generation of scientific endeavours and industries, including polymers and plastics.…”

Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance

“…Indeed, a whole new field of investigation was founded on those early expeditions toward the two beautiful sister molecules brevetoxins A and B. 32,45b,67,85,86 …”