Over the past fifty years, hundreds of polyyne compounds have been isolated from nature. These often unstable molecules are found in sources as common as garden vegetables and as obscure as bacterial cultures. Naturally occurring polyynes feature a wide range of structural diversity and display an equally broad array of biological properties. Early synthetic efforts relied primarily on Cu-catalyzed, oxidative acetylenic homo- and heterocoupling reactions to assemble the polyyne framework. The past 25 years, however, have witnessed a renaissance in the field of polyyne natural product synthesis: transition-metal-catalyzed alkynylation reactions and asymmetric transformations have combined to substantially expand access to natural polyynes. This Review recounts these synthetic achievements and also highlights both the natural source(s) and biological relevance for many of these compounds.

Synthesis of Naturally Occurring Polyynes

In one step, the skeleton of cis-spirovetivanes was constructed with high stereoselectivity by the phosphine-catalyzed [3+2] cycloaddition reaction of tert-butyl 2,3-butadienoate or 2-butynoate with 3-methyl-2-methylenecyclohexanone (5). This method was exemplified by the first highly efficient total synthesis of natural product (-)-hinesol, which is an active ingredient of cerebral circulation and metabolism improvers.

A phosphine-catalyzed [3+2] cycloaddition strategy leading to the first total synthesis of (-)-hinesol.

The structures of natural products from a variety of sources contain spirocycles, two rings that share a common atom. The spiro motif is finding increasing inclusion in drug candidates, and as a structural component in several promising classes of chiral ligands used in asymmetric synthesis. Total syntheses of products containing all-carbon spirocycles feature several common methods of ring closure which we examine in this review.

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Total syntheses of natural products containing spirocarbocycles

Synthese von Polyin‐Naturstoffen

Publisher Summary This chapter presents the chemistry of furans and shows that there are still many possibilities for further investigation. Furans undergo electrophilic substitution with exceptional ease, if there are no electron-withdrawing groups in the ring. The decarbonylation of furfural to give furan is best carried out at high temperatures. Catalytic dehydrogenation of dihydrofurans is unsatisfactory as in several cases secondary reactions take place. The addition reaction to the furan ring that has been by far the most studied is certainly the catalytic hydrogenation of the ring. It has been shown in the numerous publications on this reaction that various classes of compounds can be obtained-alcohols, ketones, hydrocarbons, ethers, and others. The chapter explores two elimination processes that go through the furan ring and lead to aromatization. Ring cleavage in the furan system is usually obtained by catalytic hydrogenolysis. The chapter presents the examples of addition reactions and conversion reactions and discusses the oxidative ring opening.

The development of the chemistry of furans, 1952-1963*

The sesquiterpenoid alcohol, the so-called atractylol, a major constituent of the essential oil from the rhizomes of Atractylodes lancea DE CANDOLLE (Compositae), was separated into the known eudesmol and a new sesquiterpenoid alcohol, hinesol, which were characterised. Association of the two alcohols was established unambiguously by the regeneration of the so-called atractylol from them.

Yasuko Sasaki

Papers

Studies on the Constituents of Atractylodes. III. Separation of Atractylol into Eudesmol and Hinesol.

Studies on the Constituents of Atractylodes. VI. : The Structure of Atractylodin. (1). : The Skeleton.

Structure of Hinesol

Studies on the Constituents of Atractylodes. VIII. : The Structure of Atractylodin. (3). : Synthesis.

Studies on the Constituents of Atractylodes. VII. : The Structure of Atractylodin. (2). : The Chromophores.