Pentalenolactone methyl ester

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... 

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

These allylpalladation-acylpalladation cascade bicyclization reactions have been applied mainly by Oppolzer to the synthesis of various natural products including (zb)-pentalenolactone E methyl ester [152], 3-isorauniti-cine [153], ( )-coriolin [154], and ( )-hirsutene [155]. Their application to the syntheses of [5.5.5.5]fenestrane derivatives by Keese [156,157] (Scheme 63) is also noteworthy. 

Intermolecular cyclopropanation reactions with ethyl diazoacetate have been employed for the construction of the cyclopropane-containing amino acid 7 (equation 25) Thus, rhodium(II) acetate catalysed decomposition of ethyl diazoacetate in the presence of d-cbz-vinylglycine methyl ester 5 afforded cyclopropyl ester 6 in 85% yield. Removal of the protecting group completed the synthesis of 7. Another example illustrating intermolecular cyclopropanation can be found in Piers and Moss synthesis of ( )-quadrone 8" (equation 26). Intermolecular cyclopropanation of enamide or vinyl ether functions using ethyl diazoacetate has also been used in the synthesis of eburnamonine 9", pentalenolactone E ester 10" and ( )-dicranenone A11" (equations 27-29). 

Hua has used the products of Pauson-Khand cycloadditions for syntheses of optically active pental-enene and racemic pentalenolactone E methyl ester. The racemic ketone in the first case was converted to the necessary optically active intermediate by kinetic resolution via 1,4-addition of an optically active allyl sulfoxide anion. These represented the first synthesis of natural products containing the angularly fused triquinane skeleton from bicyclic Pauson-Khand products (equation 53 and Scheme 20). ... 

Stereospecific 1,4-addition of the carbanion (78) to (siloxymethyl)bicyclooctenone (84) yields mainly the corresponding l,4- y-adduct. In seven steps, this adduct is converted into the known b-lactol (85), from which pentalenolactone ( 0-methyl ester (86) may then be derived (Scheme 23)7 ... 

Paquette et a/.182 have accomplished a relatively short synthesis of the methyl ester of pentalenolactone E (372) (Scheme 43). Full details of the biosynthesis of pentalenolactone (373) from [t/-13C6] glucose and [6,6-2H2] glucose have been reported.183 These substrates were used in view of the lack of incorporation of the more conventional acetate and mevalonate isoprenoid precursors. The stereochemical picture which has emerged from this study is that the pentalenane... 

An application of this methodology is the preparation of a key intermediate in the synthesis of the methyl ester of ( )-pentalenolactone E (22) by the use of palladium-catalyzed metallo-ene cycl iza tion/methoxyca r bony la tio n7 °. 

Taber and co-workers also showed that diazocarbonyls undergo C—H insertion reactions in the presence of rhodium acetate [Rh2(OAc)4].3i0b,3ll jaber and Schuchardt used this method for the conversion of 393 to 394 (91% yield) in a synthesis of ( )-pentalenolactone E methyl ester. a-Cuparenone was also synthesized by this method.313 Undheim used this approach for the synthesis of p-oxaspirane systems.3i4 When 395 was treated with a catalytic amount of rhodium tetraacetate, for example, spiro diketone 396 was obtained in 43% yield. 

Pentalenolactone E methyl ester has been prepared as part of a demonstration of the synthetic utility of a rhodium-mediated insertion reaction as illustrated by the conversion of (71) into (72)... 

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