Cyclase, artificial

BINOL derivative SnCl4 complexes are useful not only as artificial cyclases but also as enantioselective protonation reagents for silyl enol ethers. " However, their exact structures have not been determined. SnCl4-free BINOL derivatives are... 

Ishihara, Yamamoto, and coworkers demonstrated that 26 SnCl4 is an artificial cyclase that is useful for not only achiral but also chiral substrates. The diastereo-selective cyclization of ( )-nerolidol (29) has been examined with 1 equiv of the achiral LBA, 2-methoxyphenol (32) SnCl4, in dichloromethane at —78°C (entry 1, Table 12.1). Cyclization of ( )-29 bearing an acid-sensitive allylic hydroxy group gives a complex reaction mixture, and the desired trans-fused 2-oxabicyclo[4.4.0]... 

In 1999, Yamamoto reported the first example of an enantioselective biomime tic polyene cychzation using chiral LBAs as artificial cyclases. The LBA cyclase is believed to participate in the initial enantioselective protonation of the terminal isoprenyl group which induces concomitant diastereoselective cychzation [128]. Subsequent work by the Yamamoto group led to the development of LBA 52 as an artificial cyclase for hydroxypolyprenoids (Scheme 5.68) [129]. LBA 52 mediated cychzation of the the appropriate achiral hydroxypolypreniods permitting the short total syntheses of (-)-Chromazonarol, (-i-)-8-epi-puupehedione, and (-)-ll -deox-ytaondiol (not shown). 

Despite extensive studies on acid-catalyzed diastereoselective polyene-cyclizations, their enantioselective behavior have not yet been reported. The stereochemical implications of polyene-cyclizations can be explained by the Stork-Eschenmoser hypothesis [140], and the most important feature required for an artificial cyclase is asymmetric induction during the initial protonation. Very recently, the author and Yamamoto et al. succeeded in the first enantioselective biomimetic cyclization of polypre-noids catalyzed by LB A [141]. 

Ishibashi H, Ishihara K, Yamamoto H (2004) A new artificial cyclase for polyprenoids enantioselective total synthesis of (—)-chromazonarol, (-l-)-8- epi-puupehedione, and (—)-1 L-deoxytaondiol methyl ether. J Am Chem Soc 126 11122-11123... 

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. 

In 2004, Yamamoto-Ishihara s gronp designed a new artificial cyclase 7 and nsed it for the efficient synthesis of (-)-chrt nazonarol (10) (Scheme 9.13) [15g]. The five-membered... 

Yamamoto-Ishihara s group has demonstrated that chiral LBA 7 SnCl is an artificial cyclase that is useful for... 

Chiral pyrogallol (14) derived LBA (15) was developed for enantioselective polyene cyclization reaction as an artificial cyclase by Yamamoto, Ishihara and coworkers in 2004 (Scheme 1.23) [26]. Various tricyclic skeletons have been synthesized with good enantioselectivities (79-85% ee) in the presence of chiral LBA (15). 

Chiral catechol-derived LBA (16) was devised as a new artificial cyclase for polyprenoids by the same group in 2004 (Scheme 1.24) [27]. The synthetic power of the new chiral LBA (16) has been well demonstrated by enantioselective cyclizations of various 2-(polyprenyl)phenol derivatives with good to excellent enantioselectivities (88-90% ee), leading to the efficient asymmetric syntheses of (-)-chromazonarol, (+)-8-epi-puupehedione, and (-)-ll -deoxytaondiol methyl ether. 

Subsequent study revealed that the chiral LBA (16) canbeusedas artificial cyclases for the asymmetric syntheses of (-)-caparrapi oxide (17) and (+)-8-epicaparrapi oxide (18) [28a,b]. (17) and (18) can be diastereoselectively synthesized from (S)-(19) (prepared in three steps from commercially available famesol) by reagent control of (R)-16 and (S)-16, respectively, regardless of the chirality of (S)-19 (Scheme 1.25). 

P. is - prostaglandin that is produced by enzymatic transformation of prostaglandin endoperoxides and which dilates blood vessels. P. is chemically unstable in aqueous solutions, but the mono sodium-salt is stable as a solid and in solution. In addition, p. shows antimetastatic effects and has been used for patients with acute myocardial infarction. It has also been postulated that p. acts to stimulate platelet adenylate cyclase and to prevent the action of thrombi in phospholipid breakdown as well as platelet aggregation. In clinical practice, it is used for preventing the loss of platelets in cases wdiere the blood comes into extracorporal contact with artificial surfaces, i.e., in hemodialysis, cardiopulmonary bypass, and charcoal column perfusion for treatment of liver failure. 

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