Azaphilone structure

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>. 

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... 

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... 

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... 

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. 

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... 

New azaphilones named isochromophilones III-VI (18-21) were isolated from the culture broth of Penicillium multicolor FO-3216 as inhibitors of ACAT. Their structures were elucidated by NMR and other spectroscopic analyses. The IC50 values of isochromophilones (17-20) (ACAT) activity in an enzyme assay using rat liver microsomes were calculated to be 110, 50, 50 and 120 pM, respectively [79]. 

The results in Table 3 indicate that the halogen atom at C-5 and the orientation from C-8 to C-10 in the isochromane ring of azaphilones, in addition to the diene structure in C-2 side chain, are very important for the inhibition of gpl20-CD4 binding. 

Falconensins, i.e. azaphilones esterified by chloroorselinic acid, A (35), B (36) and C (37), were isolated from mycelial extracts of the Venezuelan soil fungus ascomycete Emericella falconensis [89]. Itabashi et al. [90] later isolated falconensone H (43) together with falconensins A, B, C and D (38) from the same culture. Their chemical structures are shown below. 

Further falconensins, i.e. falconensins E (39), K (40), L (41), M (42) and N (44), were isolated also from Emericella falconensis. Three new azaphilone derivatives designated falconensins E, F and G were isolated from the mycelium of Emericella falconensis, along with falconensins A-D and H. The structures of new falconensins were established by spectroscopic investigation and chemical correlations. The absolute stereochemistry of falconensins A-G was also established [91]. 

Six new hydrogenated azaphilones designated falconensins I-N were isolated as minor components from mycelia of Emericella falconensis and/or E. fruticulosa along with nine azaphilone derivatives, falconensins A-H. The structures of falconensins I-N were determined by spectroscopic investigation and chemical correlation [92],... 

Fermentations of the ascomycete Sepedonium chrysospermum produce large quantities of (—)-chrysodin [UV/vis. (chloroform) max(log e) = 243 (3.99), 308.5 (4.12), 380 nm (4.61)] for which the aza-philone structure (390) has been proposed on the basis of chemical transformations and physical measurements 170). The absolute configuration shown for chrysodin (390) may be assigned following more recent work on the stereochemistry of azaphilone pigments 632, 714). 

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