Azaphilones

Jongrungruangchok, S. et ah, Azaphilone pigments from a yellow mutant of the fungusa Monascus kaoliang. Phytochemistry, 65, 2569, 2004. 

A microwave-driven Sonogashira coupling step is involved in the total synthesis of azaphilones, a structurally diverse family of natural products containing a highly oxygenated bicyclic core and a quaternary center. Porco and his colleagues have described the alkynylation of densely functionalized bromobenzaldehydes with... 

An Au(iii) catalyst has been used for the cyclization of <9-alkynylbenzaldehydes to benzopyrilium salts, which are readily oxidized to the corresponding azaphilones (Equation (97)).346 Similar transformations have been realized with catalytic AgSbF6 347... 

The topical antifungal agent ciclopirox (32) was formed from 2-pyrone 31 by an azaphilone reaction... 

In the presence of copper(I) salts in acidic media o-ethynyl-benzaldehyde derivatives were found to cycloisomerise to 2-benzopyrylium salts (4.26.), The reaction, although working in the absence of catalyst too, was accelerated by the addition of different metal salts. The reaction was applied in the preparation of azaphilones and related molecules.30... 

Several new fungal metabolites ( azaphilones , having an affinity for nitrogen nucleophiles) related to the well-known sclerotiorin (7) have been reported in recent years. Studies of the fungus Talaromyces luteus have uncovered luteusins A-E (144-148) (440 443). Luteusins A and B were originally named TL-1 and TL-2, and the stereochemistry of C and D was later revised (443). These metabolites have monoamine oxidase inhibitory properties. The related fungus Talaromyces helicus has furnished helicusins A-D (149-152) (444). 

Yoshida E, Fujimoto H, Yamazaki M (1996) Isolation of Three New Azaphilones, Luteusins C, D, and E, from an Ascomycete, Talaromyces luteus. Chem Pharm Bull 44 284... 

Yoshida E, Fujimoto H, Baba M, Yamasaki M (1995) Four New Chlorinated Azaphilones, Helicusins A-D, Closely Related to 7-epi-Sclerotiorin, from an Ascomycetous Fungus, Talaromyces helicus. Chem Pharm Bull 43 1307... 

Tomoda H, Matsushima C, Tabata N, Namatame I, Tanaka H, Bamberger MJ, Arai H, Fukazawa M, Inoue K, Omura S (1999) Structure-Specific Inhibition of Cholesteryl Ester Transfer Protein by Azaphilones. J Antibiot 52 160... 

Pairet L, Wrigley SK, Chetland I, Reynolds EE, Hayes MA, Holloway J, Ainsworth AM, Katzer W, Cheng X-M, Hupe DJ, Charlton P, Doherty AM (1995) Azaphilones with Endothelin Receptor Binding Activity Produced by Penicillium sclerotiorum Taxonomy, Fermentation, Isolation, Structure Elucidation and Biological Activity. J Antibiot 48 913... 

Matsuzaki K, Tahara H, Inokoshi J, Tanaka H, Masuma R, Omura S (1998) New Bromi-nated and Halogen-Less Derivatives and Structure-Activity Relationships of Azaphilones Inhibiting gpl20-CD4 Binding. J Antibiot 51 1004... 

Toki S, Tanaka T, Uosaki Y, Yoshida M, Suzuki Y, Kita K, Mihara A, Ando K, Lokker NA, Giese NA, Matsuda Y (1999) RP-1551s, a Family of Azaphilones Produced by Penicillium sp., Inhibit the Binding of PDGF to the Extracellular Domain of Its Receptor. J Antibiot 52 235... 

Itabashi T, Ogasawara N, Nozawa K, Kawai K (1996) Isolation and Structures of New Azaphilone Derivatives, Falconensins E-G, from Emericella falconensis and Absolute Configurations of Falconensins A-G. Chem Pharm Bull 44 2213... 

Ogasawara N, Kawai K (1998) Hydrogenated Azaphilones from Emericella falconensis and Emericella fruticulosa. Phytochemistry 47 1131... 

Since sclerotiorin, a member of the azaphilone family, was found to inhibit CETP activity, the effect of azaphilones on CETP activity was tested. A structure-specific CETP inhibition by azaphilones was shown. Electrophilic ketone(s) and/or enone(s) at both the C-6 and C-8 positions of the isochromane-like ring are neces-... 

Figure 6 Consensus structure of azaphilones for CETP inhibition (A) and hypothetical mechanism of reaction of sclerotiorin with e-amino residue of lysine (B).

H Tomoda, C Matsushima, N Tabata, I Namatame, H Tanaka, H Arai, M Fukazawa, K Inoue, S Omura. Structure-specific inhibition of cholesteryl ester transfer protein by azaphilones. J Antibiot 52 160-170, 1999. 

Heptyl-6,8-dihydroxy-7-methylisochromenylium 2,2,2-trifluoroacetate 109 can be oxidized using ortho- ioAobenzo ic acid (IBX) to afford the azaphilone nucleus 110 in high yield (Equation 52) <2004AGE1239>. 

This reaction type was intensively investigated by Yoshinori Yamamoto et al., who focused mainly on copper and gold.19 In the context of an application in the synthesis of azaphilones, the Porco group thoroughly compared the reactivity of the three metals in the conversion of a hydroxylated ortho-alkynylbenzaldehyde to the corresponding pyrylium salt (Scheme 12.6, Table 12.3).20... 

A correction of structure from (13) to the azaphilone structure (14) for monochaetin, a metabolite elaborated by the fungus Monochaetia compta, was made possible by examination of the long-range H—l3C connectivity pattern as determined by the heteronuclear selective population inversion (SPI) NMR technique <86JCS(P1)1975>. 

There are six well-known Monascus pigments (azaphilones) that are produced and are divided into three pairs. Rubropunctatin (C21H22O5) and monascorubrin are orange pigments with different aliphatic... 

Campoy, S., Perez, F., Martin, J. F., Gutierrez, S., and Liras, P. 2003. Stable transformants of the azaphilone pigment-producing Monascus purpureus obtained by protoplast transformation and Agrobacterium-mediated DNA transfer. Curr. Genet. 43(6), 447-452. 

The Cu-promoted enantioselective oxidative dearomatisation of aUcynylbenzaldehydes followed by a cycloisomerisation leads to azaphilones, fused 4//-pyrans (Scheme 1) <05JA9342>, while an alternative synthesis involves oxidation of a 1/7-benzopyrylium salt derived from a substituted benzaldehyde (Scheme 2) <05JOC4585>. Treatment of azaphilones with primary amines results in cleavage of the pyran ring and the formation of vinylogous y-pyridones. 

Microbial production of colored azaphilone metabolites (6,7-dihydroisochro-mene-8-one or 6,7-dihydroisoquinoline-7-one derivatives 00CLY105. 

J., Ainsworth, A. M., Katzer, W, Cheng, X.-M., Hupe, D. J., Charlton, P., and Doherty, A. M. (1995) Azaphilones with endothelin receptor binding activity produced by Peniciibum sclerotiorum taxonomy, fermentation, isolation, structure elucidation and biological activity. J Antibiot. 48,913-918... 

Production of azaphilone metabolites (including also non-halogen compounds) by filamentous fungi is summarized in Table 2. 

---