Pentalenolactones

Pentalenolactone E methyl ester (46), an angularly fused sesquiterpene lactone, was first isolated and characterized by Cane and Rossi [38]. One approach to the synthesis of this material is illustrated in Scheme 5. Key to the successful implementation of the plan is the synthesis of butenolide 49, the electrochemi-cally promoted cyclization of 49 to the tricyclic y-lactone 48, ring opening of the latter to convert the linearly fused system to the angularly fused six-membered ring lactone 47, and functional group elaboration leading to the natural product 46 [36,37]. 

This strategy [20b] has been applied, for instance, in a total synthesis of pentalenolactone E methyl ester (27) (Scheme 5.17), and more recently Marino and Long [20c] have described the intramolecular version of this annulation procedure to synthesise an octahydronaphthalene derivative (28) which is a key intermediate for a new synthesis of dihydrocompactin (Scheme 5.18). However, the reaction with aldehydes affords only very low yields of a mixture of lactones. 

In the course of biosynthetic experiments involving Streptomyces UC5319, Cane and Rossi treated the acidic fraction of an ether extract with diazomethane and obtained 600 which they called pentalenolactone E methyl ester Paquette s solution to the total synthesis of this substance (Scheme LI) was founded upon a... 

Recently, the oxygen-free neutral precursor to the pentalenolactone family of metabolites was isolated, identified as 759, and named pentalenene Annis and Paquette have since devised a synthesis of 759 which efficiently elaborates its ring junction quaternary center and three angularly fused cyclopentane rings Condensation... 

The fermentation broth of various Streptomyces species can be separated into an acidic fraction shown to contain pentalenic acid 776) The somewhat less oxidized pentalenolactone precursor has been independently prepared from humulene from which is is probably derived biogenetically Thus, treatment of humulene with mercuric nitrate followed by aqueous potassium bromide solution gave two bromo-mercury derivatives which were oxygenated in the presence of sodium borohydride. The resulting pair of diols (770 and 771) were separately converted to exo methylene... 

Intramolecular [2 + 2] photocycloadditions of 3-alkenylcyclopent-2-enones represent the key step in the total synthesis of various natural products, e.g. pentalenolactone 6-methyl ester19 and pentalenic acid,20 as well as in the preparation of strained fenestranes21 and laurenene.22 Similarly, the photoisomerization of 3-alkenylcyclohexcnoncs to tricyclo[6.3.0.01-6]undecanones are steps in the syntheses of tricyclic sesquiterpene isocomene23 and precursors to members of the acorane family.24... 

Likewise, the organopalladium-catalyzed reaction of ethyl 2-(3,3-dimethyl-4-oxo-7-trimethyl-siloxy-7-vinylbicyclo[3.2.0]hept-l-yl)acetate provided ethyl 2-(3,3-dimethyl-8-methylene-4,7-dioxobicyclo[3.3.0]oct-l-yl)acetate (9), which is a viable precursor of the pentalenolactone-G and pentalenolactone-H antibiotics.26... 

The product (2) is an intermediate in a synthesis of pentalenolactone E methyl ester (3), a sesquiterpene antibiotic.2... 

Although the first survey listed 45 natural chlorinated sesquiterpene lactones, several such compounds were omitted in that coverage (1) and are described here. The novel sesquiterpene lactone chlorochrymorin (239) was isolated from Chrysanthemum morfolium (499), and the chlorohydrin graminichlorin (240) is found in Liatris graminifolia (500). The antibacterial AA-57 (241), which is related to pentalenolactone, is produced by a Streptomyces sp. (501). The plant Eupatorium chinense var. simplicifolium has yielded eupachifolin D (242) (502) (side-chain double bond stereochemistry revised (518)), and the new guaianolide andalucin (243) was characterized from Artemisia lanata (503). The previously known chlorohyssopifolins (1) have been studied for cytostatic activity, and the presence of one and even two chlorine atoms amplifies this activity (504). 

Heathcock required diester 23 for his synthesis of the antibiotic pentalenolactone.3 Reconnecting the esters gives the cyclohexene 24. We must change the two ether groups into carbonyl groups and one obvious starting material is 25, the Diels-Alder adduct of butadiene and maleic anhydride 26. 

Acidic lipophilic antibiotics pentalenolactones (69,70), active against Grampositive and Gram-negative bacteria including acid-fast bacteria, were isolated [68] from Streptomyces sp. 

Pentalenolactone is the name given to an antibiotic extracted from Streptomyces fungi with an Interesting tricyclic structure. 

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