Lactones biological importance

D-Ribonolactone is a convenient source of chiral cyclopentenones, acyclic structures, and oxacyclic systems, useful intermediates for the synthesis of biologically important molecules. Cyclopentenones derived from ribono-lactone have been employed for the synthesis of prostanoids and carbocyclic nucleosides. The cyclopentenone 280 was synthesized (265) from 2,3-0-cyclohexylidene-D-ribono-1,4-lactone (16b) by a threestep synthesis that involves successive periodate oxidation, glycosylation of the lactol with 2-propanol to give 279, and treatment of 279 with lithium dimethyl methyl-phosphonate. The enantiomer of 280 was prepared from D-mannose by converting it to the corresponding lactone, which was selectively protected at HO-2, HO-3 by acetalization. Likewise, the isopropylidene derivative 282 was obtained (266) via the intermediate unsaturated lactone 281, prepared from 16a. Reduction of 281 with di-tert-butoxy lithium aluminum hydride, followed by mesylation, gave 282. 

Lundt I (2003) Iminosugars, isoiminosugars, and carbasugars from activated carbohydrate lactones efficient synthesis of biologically important compounds. In Witzak ZJ, Tatsuta K (eds) Carbohydrate synthons in natural products chemistry synthesis, functionalization and applications. ACS Symposium Series, vol 841. American Chemical Society, Washington, DC,pp 117-140... 

Iminosugars, Isoiminosugars, and Carbasugars from Activated Carbohydrate Lactones Efficient Synthesis of Biologically Important Compounds... 

Andreana et al. [25] have recently invoked RCM to prepare /J,y-unsaturated <5-lactones (Scheme 3). Exposure of dienes of general type 13 to either 2 or 4 (which could be used at lower loadings) readily furnished lactones 14. For other examples of a,/ -unsaturated <5- and y-lactone synthesis by RCM see Ref. [26]. Variation of the configuration at the chiral carbons and the ligand for the asymmetric dihydroxylation reaction allows access to an array of biologically important dideoxy-sugar derivatives. 

The synthetic utility of this procedure was illustrated by the practical synthesis of the versatile intermediate y-lactone (i )-5-methyltetrahydrofuran-2-one (Fransson et al, 2005). Chiral y-lactones are important structural syn-thons for the synthesis of natural products and biologically active compounds (Benincori et al, 2004). 

Several lactones have important biological activities. 

The macrocyclic trichothecane lactonic esters are a biologically important class of compounds produced by various species of the Myrothecium group of microorganisms. This family of substances has exhibited marked biological activity... 

Functionalized y-lactones are important synthetic intermediates for a number of biologically active natural products [102]. An interesting strategy based upon the AD reaction of unsatuxated esters or carbamates, combined with the spontaneous kinetic cycHzation to form five-membered ring lactones, has recently been established (Scheme 27). Thus, asymmetric dihydroxylation of p,y- and y,8-un-saturated esters 73 and 74 results in the hydroxyl-substituted lactones 75 or the side-chain functionaUzed system 76 respectively, in high optical purity. This strategy was appHed to the synthesis of numerous natural products. 

B.ii. Synthetic Approaches to Macrocyclic Lactones. There are many examples of biologically important, naturally occurring lactones. A variety of cyclization techniques have been developed, but all are based on the idea that the carbonyl end of an cu-substituted acid is activated to facilitate attack by or at the other functionalized end. Trifluoroacetic anhydride, for example, was used to convert 220 to 222 in 31% yield.xhe initially formed mixed anhydride (221) activated the carbonyl to attack by the hydroxyl moiety, leading to 222 in the Taub et al. synthesis of zearalenone. An alternative synthetic route required a macrocyclization reaction but it involved Friedel-Crafts acylation (sec. 12.4.D). Cyclization has also been observed using a mixture of trifluoroacetic acid and trifluoroacetic anhydride. ... 

Kita and coworkers have developed a simple and reliable method for the direct constmction of biologically important aryl lactones 573 from carboxylic acids 572 using a combination of PhI(OAc)2 with NaBr (Scheme 3.226). The mechanism of this reaction includes initial generation of carbonyloxy radical followed by intramolecular benzylic hydrogen abstraction and cycUzation [618]. 

The a-methylene-y-lactone unit is a common feature in many biologically important products and a useful synthesis of this unit fused to a carbocyclic ring... 

As a result of the biological importance of these natural products, the synthesis of polysubstituted a-methylene y-lactones has been of interest to synthetic chemists for several decades. Several routes have been devised to access the a-methylene y-lactone ring however, they tend to be lengthy and cumbersome if the lactone contains any sort of substitution. A review by Hoffmann and Rabe in 1985 discussed some of the methods developed up to that day for the preparation of a-methylene y-lactones (Figure 2). ... 

The biological importance of 8-lactones has sparked enormous interest among the synthetic chemists and led to the development of a wide variety of powerful methods for their synthesis. In this chapter, a brief review on selected approaches for the construction of the saturated 8-lactone framework is presented, focusing mainly on the ring-closing steps. We have to point out that methods for the synthesis of unsaturated 8-lactones and their derivatization to saturated 8-lactones are beyond the scope of this chapter. 

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. 

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