Chromazonarol

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). 

Chromazonarol, a minor constituent of the brown Pacific seaweed, has been synthesized using LBA-promoted enantiose-lective cyclization. The cyclization of 4-benzy loxyphenyl farnesyl ether with (5)-LBA gives the desired tetracyclic compound as the major diastereomer in 44% ee (eq 13). 

A carbocationic intermediate is probably involved in the Pd- and Pt-catalysed cyclisations of dienylphenols. Reduction of the initial products affords fused chromans with a trans ring junction (Scheme 7) <04AG(E)3459, 04T7405>. A similar enantioselective polyeyclisation has been performed using a chiral Sn complex by which total syntheses of (-)-chromazonarol and (-l-)-8-ep/-puupehedione have been achieved <04JA11122>. 

Assignment of the trivial name 8-epichromazonarol to the metabolite 3 7 isolated from Smenospongia aurea is misleading since it implies a stereochemical relationship with chromazonarol (an algal metabolite) that has not be established. The arbitrary absolute stereochemistry depicted in this review is more closely related to that of the known sponge metabolite ent-chromazonarol, rather than the algal metabolite chromazonarol. In fact the absolute stereochemistry of 37 remains unknown. 

Dysidea pallescens 3 8 Gum (alo riot reported (acetate, (a)o -r39° (CHCI3)) Comparison to chromazonarol... 

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... 

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. 

Originally presented as derivatives of drimane (Fenical et al., 1973), it was established and confirmed by stereoselective synthesis, that zonarol and its derivatives have the carbon skeleton of ent-drimane (Welch and Rao, 1977a, 1978). Zonarone and isozonarone - the quinonic equivalents of zonarol and isozonarol - were prepared by oxidation of the latter, but could be intermediates in the biosynthesis of cyclozonarone, chromazonarol, and iso-chromazonarol which were isolated from Dictyopteris undulata (Fenical and McConnell, 1975). The probable biogenetic relationships between these compounds are summarized in Figure 14.13 (Kurata, Taniguchi, and Suzuki, 1996). 

Barrero, A.F., Alvarez-Manzaneda, E.J., Herrador, M.M., Chahbotm, R., and Galera, P. (1999) Synthesis and antitumoral activities of marine ent-chromazonarol and related compounds. Bioorg. Med. Chem., 9, 2325-2328. 

Fenical, W. and McConnell, O. (1975) Chromazonarol and isochromazonarol, new chromanols from the brown seaweed Dictyopteris undulata. Experientia, 31,1004—1005. 

In addition to being a rich source of furanoid sesquiterpenes, the sponge Disideapallescens has also yielded 191) a chromansesquiterpenoid, /-chromazonarol (237), which is the antipodal cyclic isomer of the algal hydroquinone zonarol (114). The biosynthesis of antipodal terpenoids by different organisms is of considerable interest. 

Cimino, G., S. De Stefano, and L. Minale /1 Chromazonarol, a Chroman-Sesquiterpenoid from the sponge Disidea pallescens. Experientia 31, 1117 (1975). 

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