Ortho-lithiated styrenes or ortho-lithiated benzaldehyde dimethyl acetals were added to 2,2-dimethoxypent-4-enals 7. The resulting alcohols were carried on to the aromatic dienones 10. These were ring-closed by olefin metathesis. Hydrolysis of the dimethyl ketal moiety and enolization provided the 3,4-benzotropolones 5. Overall, this access comprises 4-6 steps and totaled a 22-81% yield.

Type-18 or -23 benzocycloheptadienones are readily prepared by ring-closing olefin metatheses. Adding Br to 23 and eliminating HBr gave the bromoolefin 28 using DBU or its isomer iso-28 using DABCO, both with near-perfect regiocontrol. Both 28 and iso-28 underwent Sonogashira, Suzuki, Negishi, and Heck couplings as well as Pd-catalyzed alkoxycarbonylations. Hydrolysis of the resulting α-ketoketals and enolization of the liberated α-diketones delivered a portfolio of hitherto unknown 3,4-benzotropolones. The 8-ethoxycarbonylated dimethyl-3,4-benzotropolone 50 obtained by this route was dimethylated to give goupiolone A (52). This synthesis encompasses 9 steps from 22, that is, half as many as the only previous synthesis (19 steps). A variant of our route afforded the 1,8-dibromide 54. Coupling with excess phenylboronic acid and ketal hydrolysis provided the diphenylated benzotropolone 56 and suggests a strategy, by which the natural bispulvinone aurantricholone (7) might be reached.

Five fungal genomes from the Ascomycota (sac fungi) were found to contain a gene with sequence similarity to a recently discovered small group of bacterial prenyltransferases that catalyze the C-prenylation of aromatic substrates in secondary metabolism. The genes from Aspergillus terreus NIH2624, Botryotinia fuckeliana B05.10 and Sclerotinia sclerotiorum 1980 were expressed in Escherichia coli, and the resulting His 8 -tagged proteins were purified and investigated biochemically. Their substrate specificity was found to be different from that of any other prenyltransferase investigated previously. Using 2,7-dihydroxynaphthalene (2,7-DHN) and dimethylallyl diphosphate as substrates, they catalyzed a regiospecific Recently, a new family of prenyltransferases has been discovered in bacteria of the genus Streptomyces (1-4). They are involved in the biosynthesis of secondary metabolites, e.g. antibiotics. The members of this family are characterized by a new protein fold, termed PT barrel (1). The PT barrel consists of five repetitive ␣␣␤␤ elements, with the ␤ strands forming a central barrel. In contrast to the TIM barrel, the PT barrel consists of 10 antiparallel ␤ strands and contains the active site of the enzyme in its spacious lumen. The members of this enzyme family catalyze Friedel-Crafts alkylations of aromatic substrates, i.e. the formation of carbon-carbon-bonds between C-1 or C-3 of the isoprenoid substrate and an aromatic carbon of the acceptor substrate. In contrast to the membrane-bound aromatic prenyltransferases of ubiquinone, menaquinone, and plastoquinone biosynthesis (5), the enzymes containing the PT barrel are soluble proteins and do not contain (N/D)DxxD motifs for binding of the isoprenoid substrate.

A stereoselective synthesis of the title compounds was developed. Hexane-and amine-free THF solutions of α-lithiated lithium arylacetates ('arylacetic acid dianions') were aldol-added to 3-arylpropynals. This gave 2,5-diaryl-3-hydroxypent-4-ynoic acids with up to a 72:28 preference for the anti-diastereomer (27 examples + 1 exception). When treated with Ag 2 CO 3 (1-20 mol%) in DMF at room temperature for 2.5 days, the respective mixtures underwent regio-and stereoselective lactonizations followed by an in situ dehydration. Thereby 3-aryl-5-(arylmethylidene)butenolides were obtained with a Z-configuration of the oxygenated C=C bond. Their overall yields ranged from 46% to 83% (1 exception: 28%). Three 3-aryl-5-(arylmethylidene)butenolides contained a C-Br and/or a C-I bond. They allowed a subsequent Pd-catalyzed CC coupling, which furnished follow-up butenolides.

Syntheses of 3,4-Benzotropolones by Ring-Closing Metatheses. -For the first time, a nonbenzenoid aromatic such as tropolone is obtained via ring-closing metathesis. Using three different approaches, a series of mostly unknown 3,4-benzotropolones is synthesized. -(ARICAN, D.; BRUECKNER*, R.; Org. Lett. 15 (2013) 11, 2582-2585, http://dx.doi.org/10.1021/ol400510j ; Inst. Org. Chem., Albert-Ludwigs-Univ., D-79104 Freiburg/Br., Germany; Eng.) -H. Haber 39-054