Pentalenolactone F, a new metabolite isolated from streptomyces. Isolation and structure elucidation.

Since the isolation and identification of the sesquiterpene antibiotic pentalenolactone (1),1-7) several other related metabolites have been recognized in strains of Streptomyces, notably pentalenolactones E (2),8,9) G (3),10) and H (4),11) pentalenic acid (5),11,12) and the parent hydrocarbon, pentalenene (6).11-15)* Besides their novel structural features, these compounds are all potential intermediates or shunt metabolites in the biosynthesis of pentalenolactone, whose mevalonoid origin we have recently established.''? We wish to report here a new metabolite, pentalenolactone F (7), isolated as the methyl ester, whose structure has been established based on the spectroscopic data reported below. Treatment of the acidic extract from 2.4 liters of Streptomyces UC5319 with ethereal diazomethane gave a mixture of crude methyl esters which were purified by flash column chromatography using benzene ethyl acetate (5: 1). The fractions containing pentalenic acid (5) methyl ester were further purified by preparative layer chromatography (silica gel, benzene ethyl acetate, 5: 1) to give a mixture of the methyl esters of 5 and a new compound (7) which appeared together as an unresolved spot by TLC analysis. The final separation of these two substances was performed by HPLC using a hexanes ethyl acetate, (1: 1) mixture as eluant to give pure 5 and 7 methyl esters. The high resolution mass spectrum of 7 methyl ester established the elemental composition as C18H20O5 and suggested that the new compound was a sesquiterpene. The infrared spectrum exhibited bands characteristic of a lactone (1765 cm-1), an ester (1710 cm-1), and a double bond (1630 cm-1) but no hydroxyl absorbtion, thereby accounting for four of the five oxygen atoms and suggesting the presence of four rings and an ether function. Structure 7 was assigned based on analysis of the proton and 13C NMR spectra. The 250 MHz 'H NMR spectrum of 7 methyl ester showed a broad triplet at o 6.88, characteri-