Lactones natural products

A synthetic application of the sonolysis of iron carbonyls is the preparation of useful ferrilactones. The alkenyl epoxides (2, R = H, Ph, 1-hexanyl) are smoothly converted to the corresponding ferrilactone complexes (3) on reaction with Fe2(CO)9 suspended in THF and sonicated at room temperature [53]. Such complexes undergo several synthetically useful transformations (Scheme 3.7) including oxidation with Ce(IV) as a route to P-lactone natural products or P-lactam antibiotics and reaction with CO to afford 5-lactones [54]. Somewhat surprisingly this reaction is efficient even in diethyl ether, a volatile solvent which delivers low cavitation energy. 

Butenolides constitute a major class of lactone natural products which have been shown to play important roles in cancer chemotherapy [75]. It was previously noted that introduction of a double bond in conjugation with the lactone carbonyl results in shielding of the carbonyl NMR chemical shift for example compare the carbonyl chemical shift of 44 and 48 [74]. However,... 

A number of oxacyclic natural products were synthesized via carbocycle-forming radical reaction of oxacyclic intermediates. An early example is the synthesis of (-)-dihydroagarofuran (170) by Biichi [109] (Scheme 58). The bridgehead chloride 168 obtained from the corresponding hydroxy ketone was amenable to radical cycliza-tion, and the tricyclic ether 169 was duly obtained. The aplysin synthesis [110] provides another example, and (—)-karahana ether (173) was synthesized via radical cyclization of the substrate 171 [111] (Scheme 59). Lactonic natural products (-1-)-eremantholide A [112], alliacolide [113], and (-)-anastrephin [114] were prepared via a variety of carbocycle-forming radical cyclization reactions. In the total synthesis of spongian-16-one (176) [115] (Scheme 60), the butenolide moiety in the substrate 174 served as the final radical acceptor for three consecutive 6-endo-. rig cyclizations. 

Salinosporamides are a family of y-lactam-p-lactone natural products discovered in 2003 with the isolation of salinosporamide A from Salinispora tropica obtained from marine sediment from the Bahamas and from depths as great as -1100 m. The complete structural assignment 86 to salinosporamide A was accomplished by spectral analysis and by a single-crystal X-ray diffraction study (Figure 4.41) [207]. The pronounced anticancer activity of 86, as a 20S proteasome inhibitor, with IC50 values... 

The y-lactone natural product muricatacin 1 is a member of the class of biologically active Annonaceous acetogenin family. Muricatacin was isolated from the seeds of Annona muricata L., a variety of apple trees grown commercially in the Caribbean and Central America, by McLaughlin and co-workers in 1991 [1, 2]. Muricatacin exists namrally as a mixture of syn enantiomers in an approximate ratio of 62 38 ( 24 % ee) of (-)-muricatacin (41 , 5R) versus (+)-muricatacin (45, 55) (Fig. 3.1). These 5-hydroxy-y-lactones are comprised of adjacent chiral centres, one of which is incorporated into the lactone framework, with a dodecyl alkyl chain extending from the hydroxy bearing carbon atom. 

Indeed, this provides a rapid entry to a,P-unsaturated lactone natural products such as massoialactone and parasorbic acid [268]. Alternatively, carbonylation at lower temperatures (90 °C) and high CO pressures (200 to... 

Of the simpler 8-lactone natural products, syntheses of malyngolide, mevalonolactone, and an oviposition-attractant pheromone of a mosquito ... 

In view of the biological importance of the 6-lactone moiety, extensive efforts have been devoted for the development of various methods for the synthesis of saturated 8-lactones. Ammig the various methods, the more classical methods include lactonization of the 8-hydroxy acid derivatives, Baeyer-Villiger oxidation of cyclopentanones, and oxidation of lactols. Besides, more challenging and attractive methods such as oxidative lactonization, radical cyclization, and carbonylatimi have also been used efficiently for the synthesis of 8-lactones. The past two decades have witnessed remarkable growth in the development of catalytic and asymmetric methods for the synthesis of 6-lactones in optically pure form. In the next decade, new and more exciting advances in the development of efficient and catalytic enantioselective methods and their application in the synthesis of complex 8-lactone natural products can be expected. 

Many natural products are lactones and it is not unusual to find examples m which the ring size is rather large A few naturally occurring lactones are shown m Figure 19 8 The macrohde antibiotics of which erythromycin is one example are macrocychc (large ring) lactones The lactone ring of erythromycin is 14 membered... 

The avermectins are closely related to another group of pesticidal natural products, the milhemycins. First described by Japanese workers, milhemycins were later found to be more abundant in nature than the avermectins (7—12). Both the avermectins and milhemycins are sixteen-memhered lactones, with a spiroketal system containing two six-memhered rings. The principal difference between them is that the avermectins have an a-L-oleandrosyl-a-L-oleandrosyl disaccharide attached at the 13-position whereas the milhemycins have no 13-substituent. Milhemycin stmctures are shown in Figure 2. 

Atroposelective cleavage of configurationally unstable lactone cycle in biaryl derivatives as effective route to chiral natural products and useful reagents 99S525. 

Development and applications of new reactions for construction of basic structures of natural products, in particular proapoporphine alkaloids and lactones 99YZ357. 

The results obtained showed that carbon, oxygen, or nitrogen functionalities are readily introduced into the a,p positions of the lactone moiety. In this way, useful precursors for natural product synthesis are accessible (88TL5317). 

The Baeyer-Villiger oxidation is a synthetically very useful reaction it is for example often used in the synthesis of natural products. The Corey lactone 11 is a key intermediate in the total synthesis of the physiologically active prostaglandins. It can be prepared from the lactone 10, which in turn is obtained from the bicyclic ketone 9 by reaction with m-chloroperbenzoic acid (MCPBA) " ... 

Natural product total syntheses are particularly valuable when they are attended by the development of general utility methods of synthesis. In some instances, the successful completion of a natural product total synthesis requires the development and application of a new synthetic method. The total synthesis of erythronolide B by Corey et al. is one of these instances. The double activation macro-lactonization method was a fruitful innovation that was introduced in response to the challenge presented by the macrocyclic structures of the erythromycins. Several other methods to achieve the same objective, and numerous applications followed. 

With the polycyclic framework of the natural product intact, the completion of the total synthesis only requires a short sequence of reactions. At this juncture, the decision was made to address the problem of reconstituting the A-ring lactone. It was hoped that a selective oxidation of the A-ring allylic ether could be achieved. 

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