Enantioselective synthesis of natural (-)-austalide B, an unusual ortho ester metabolite produced by toxigenic cultures of Aspergillus ustus

New Austalides from the Sponge‐Associated Fungus Aspergillus sp.

“…[21,22] Thus, 1 was identified as the 22-OMe derivative of austalide B and named austalide M. Because the austalide skeleton is derived from 6-[(2E,6E)-farnesyl]-5,7-dihydroxy-4-methylphthalide, which is biosynthesized through a mixed polyketide-terpenoid pathway with subsequent cyclization and oxidative modification, [21,42,43] the C-22 benzylic substituent must be introduced after the cyclization.…”

“…The assignment of the absolute configuration of previously reported austalides A-L, [12,13] which have versatile skeletons, relies on the single-crystal X-ray analysis of the dicamphanate ester derivative of austalide D, [21] and on the enantioselective synthesis of austalide B. [22] Electronic circular dichroism (ECD) properties of austalides have not yet been reported and correlated with the absolute geometry, but this approach would provide a straightforward way for the configurational assignment of new derivatives. ECD, supported by time-dependent density functional theory electronic circular dichroism (TDDFT) calculations, of solution conformers is a powerful microscale tool for the determination of absolute configuration of conformationally less flexible derivatives, which, in contrast to the use of Mosher's method, does not require derivatization.…”

Methodology for the Construction of the Bicyclo[4.3.0]nonane Core

“…Dihydroxylation with OsO4/NMO, and protection with SEM-Cl gave 33. Baeyer-Villiger oxidation with mCPBA was found to occur in the A ring first, and allowed for Hydrindane 1 again found use in the total synthesis of austalides, meroterpenoids from Aspergillus ustus (see Scheme 6) [24,25]. In this work, protection of 1 followed by Birch reduction in the presence of MeI gave 30, which was then treated with acid and 4-chlorobutan-2-one to give 31 as a single diastereomer.…”

A facile regioselective construction of spiro epoxy-bridged tetrahydropyranone frameworks

“…Reactions of a-diazo ketone 6 with cyclic ketones such as cyclohexanone and 6-methoxy-1-tetralone in the presence of Rh 2 (OAc) 4 catalyst were carried out to afford the corresponding cycloadducts 7,8 in 35 and 30% yields, respectively (Scheme 2). The 1 H NMR spectrum of the respective crude reaction mixture for these reactions revealed the formation of only one cycloadduct (7) and a mixture of diastereomers in the ratio of 1:6.6 (8). Surprisingly, treatment of a-diazo ketone 6 with 2-adamantanone did not afford any cycloaddition product.…”

“…Especially, the chemistry of tandem rhodium(II)-induced cyclization-1,3-dipolar cycloaddition of a-diazo ketones to C -C multiple bonds has been extensively studied to synthesize epoxy-bridged polycyclic compounds. 2a, 3 The epoxy-bridged tetrahydropyranone units are recognized as common structural units in naturally occurring bioactive molecules such as brevicomins, 4 zaragozic acid, 5 frontalin, 6 amberketal, 7 austalide B, 8 loukacinols, 9 xanthane epoxide, 10 sporol 11 and isogosterones. 12 Especially, spiro compounds containing one or more heteroatoms represent an important group of naturally occurring substances characterized by their pronounced biological importance.…”