Terpenoids polyene cyclizations

Polyene cyclizations have been of substantial value in the synthesis of polycyclic natural products of the terpene type. These syntheses resemble the processes by which terpenoid and steroidal compounds are assembled in nature. The most dramatic example of biological synthesis of a polycyclic skeleton from a polyene intermediate is the conversion of squalene oxide to the steroid lanosterol. In the biological reaction, the enzyme presumably functions not only to induce the cationic cyclization but also to bind the substrate in a conformation corresponding to the stereochemistry of the polycyclic product.21... 

Conventional multistep synthesis of natural products reduces the overall yield of the target molecules. In contrast, biomimetic enantioselective domino reactions, promoted by small-molecule artificial enzymes, are more useful for the practical synthesis of natural products and related compounds. The stereoselective formation of polycyclic isoprenoids by the cyclase-induced cyclization of polypren-oids is one of the most remarkable steps in biosynthesis because this reaction results in the formation of several new quaternary and tertiary stereocenters and new rings in a single step. The use of biomimetic polycyclization with artificial cyclase is the most ideal chemical method for the synthesis of these polycyclic terpenoids. In this chapter, biosynthesis of polycyclic terpenoids, biomimetic stereoselective polyene cyclization induced by artificial cyclases, and total synthesis of bioactive natural products using stereoselective polyene cyclization as a key step will be discussed. 

Enanlio- and diastereoselective polyene cyclization reactions promoted by small-molecule artificial enzymes have been developed as key steps for the practical synthesis of polycychc terpenoids based on biosynthetic pathways. Several examples as highlighted previously exist in the hterature mimicking the all chair transition state of the nonsterol folding, hi sharp contrast, there have been no successful examples of the polyene cyclization via a chair-boat transition state like sterol folding. In near future, more efficient and more effective catalytic biomimetic polyene cyclization reactions are expected to be developed. 

Organo-SOMO catalysis was also applied to polyene cyclization. In 2010, MacMillan reported an enantioselective cyclization reaction of substrates 41 for accessing steroidal and terpenoidal frameworks. They used imidazolidinone 40 instead of catalyst 23, with the aid of copper(ll) triflate as the oxidant. The polyene cyclization took place smoothly, giving polycyclic systems 42 and even more complex compounds 43 or 44 in good yields and with high enantioselectivity and exclusive diastereoselectivity (Scheme 36.12) [18]. 

Open-chain 1,5-polyenes (e.g. squalene) and some oxygenated derivatives are the biochemical precursors of cyclic terpenoids (e.g. steroids, carotenoids). The enzymic cyclization of squalene 2,3-oxide, which has one chiral carbon atom, to produce lanosterol introduces seven chiral centres in one totally stereoselective reaction. As a result, organic chemists have tried to ascertain, whether squalene or related olefinic systems could be induced to undergo similar stereoselective cyclizations in the absence of enzymes (W.S. Johnson, 1968, 1976). 

The majority of the polycyclic alkanes in nature derive from the terpenoid family (C5 isoprene units) with the principal structural variations of six and five fused rings, formed by cyclization of the polyene open terpenoids (Ciq, C15, C20, C25 - up to C4.0). 

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