Higher Terpenes and Steroids

Department of Biotechnology, Graduate School of Engineering, Nagoya University, Nagoya, Japan 

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. 

From Biosynthesis to Total Synthesis Strategies and Tactics for Natural Products, First Edition. Edited by Alexandros L. Zografos. 2016 John Wiley Sons, Inc. Published 2016 by John Wiley Sons, Inc. 

Head-to-tail coupling — OPP Head-to-tail coupling 

SCHEME 9.2 Biosynthesis of pentacyclic triteipenoids via nonsterol folding. 

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C24H36O5, Mr 404.55, cryst., mp. 174°C, [a] +323° (CH3CN), a polyketide. M. is a potent inhibitor (K,= 1 nM) of HMG-CoA-reductase, the key enzyme in the biosynthesis of higher terpenes and steroids such as, e. g., cholesterol. It is produced by Aspergillus terreus and various Monascus species. Thus, e. g., the plasma cholesterol concentration (a major risk factor for the occurrence of arteriosclerosis) decreases by ca. 50% in patients under medication with M. In the terpene metabolism HMG-CoA-reductase reduces 3-hydroxy-3-methy Iglutary 1-CoA to mevalonate. M. mimics the substrate and thus leads to inhibition of the enzyme. M. is commercially available under the tradename Meva-cor . M. was the lead structure for numerous synthetic HMG-CoA-reductase inhibitors that are now available or are being developed (Atorvastatin, Cerivastatin, Fluvastatin, Pravastatin, Simvastatin). In these derivatives the hexahydronaphthalene structure is replaced by heterocylic ring systems, see also compactin. 

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