Atrovenetin

Claisen rearrangementThe allyl ether 1 when heated rearranges and cyclizes slowly and in low yield to the dihydrobenzofuran 2. However, the dianion (NaH) of 1 rearranges in refluxing DMF mainly to the isomeric dihydrobenzofuran 3, a precursor to the antibiotic ( )-atrovenetin (4). 

Atrovenetin, (Table 12.1), herqueichrysin are related phenalones (ref. 59) and are unusual in that they both contain a trimethylfurano moiety arising from an prenyl ether since there is no 2-hydroxyl group to form a chromene ring from an adjacent C-prenyl group. Synthetic work (ref.59) has led to members of the group by the Claisen rearrangement. Thus the prenyl ether of the phenalone intermediate in DMF at 100°C directly afforded atrovenetin trimethyl ether. 

However in the same solvent containing potassium carbonate, to avoid cyclisation, from the same phenalenone trimethyl ether, a 2-(1,1-dimethyl)allyl-1,3-diketone resulted. Methylation of this trimethyl ether with diazomethane gave a major and a minor tetramethyl ether. The major product by acidic cyclisation with 4-toluenesulphonic acid and demethylation of the product with hydrogen iodide gave racemic atrovenetin and the minor product led by the same sequence of reactions to racemic demethylherqueichrysin. 

The naturally occurring phenalenone atrovenetin (238), produced by the fungus Penicillium atrovenetum, has been synthesised by a route which employs the novel, regioselective Claisen rearrangement-cyclisation (234)—> (235), together with the... 

The interrelationships between atrovenetin (1), norherqueinone (2), herqueinone (3), deoxyherqueinone (5), and the naphthalic anhydride (8) are shown in the scheme. X-Ray crystallographic analysis (17) of the ferrichloride salt of the orange trimethyl ether of atrovenetin... 

The extensive work which led to the structures of atrovenetin, nor-herqueinone, and the anhydride (8), as well as much of the chemistry of (3), has been reviewed previously in this series (21) since 1966, the structures of atrovenetin and anhydride (8) have been confirmed by synthesis (vide infra), and the configuration (R) at C-2 shown in the structures of the scheme, has been established in the case of (1) and (3) by the correlation of (1) with (—)-S-ethyl lactate (22). The controversy over the structure of herqueinone (8, 23, 24) (orientation of the Cs unit, and position of the OMe group) has been resolved in favor of structure (3). ... 

The substituted naphthalene (available in four steps from 3,4,5-trimethoxybenzaldehyde) reacted with malonic acid and polyphosphoric acid (100°, 15 min) to give the phenalenone (29), which was selectively demethylated to (30) with hydrochloric acid. The demethyl compound formed a dimethylallyl ether (31), which on heating in DMF at 100° gave the yellow trimethyl ether of atrovenetin (16). Demethylation of (16) with pyridine hydrochloride led to the racemic natural product. A more prolonged reaction between (28) and malonic acid in poly-... 

In 1956, consideration of the structure of atrovenetin (1) resulted in a proposal by Barton and co-workers (4, 20) that the main ring system of the pigment was probably derived from acetate units, with... 

Atrovenetin (1) (38) and to a lesser extent deoxyherqueinone (5) (39) have antibacterial activity against some Gram-positive organisms. Herqueinone (3) and norherqueinone (2) have no activity. 

Paul, I. C., and G. A. Sim Fungal Metabolites. III. The Structure of Atrovenetin X-ray Analysis of Atroventin Orange Trimethyl Ether Ferrichloride. J. Chem. Soc. (London) 1097 (1965). 

Brooks, J. S., and G. A. Morrison Absolute Configuration of Atrovenetin and Related Compounds. Chem. Commun. 13S9 (1971). 

Biichi et al. reported the total synthesis of atrovenetin via a base-promoted site-selective Claisen rearrangement followed by the formation of a benzofuran framework 111 [83]. 

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