Lactones naturally derived

The chiral lactone alcohol derivative (178)181) can be readily prepared from natural (S)-glutamic acid, the cheapest chiral a-amino acid. Lactone (178) was alkylated to yield optically active 3-substituted lactone alcohol derivatives, (179) and (180), which were intermediates in the stereoselective synthesis of various natural products 182). 

The compounds covered in this section include dihydropyranones, tetrahydropyranones and their benzologues (dihydrocoumarins, chromanones and isochromanones). The area of greatest interest is undoubtedly the chromanones because of their relationship to a number of natural products and presumably also because of their ease of formation, stability and value as precursors of other heterocycles. Tetrahydropyran-2-ones comprise one of those nebulous areas of heterocyclic chemistry and usually feature in text books as 5-lactones under derivatives of hydroxy acids. 

This cyclization has been used for a synthesis of enterobactin (5), a natural iron carrier (previous synthesis, 8, 215-216) by cyclization of a linear trimer of serine. Thus the lactone 3, derived from i.-serinc, cyclizes in the presence of 1 to the tricyclic lactitnc 4 in 23% yield. This product was converted into 5 by dctritylation and acylation. ... 

Among the 24-membered lactones, one derived from natural sophorolipid was polymerised via lipase-catalysed ROP to form a glycolipid-based polyester [118]. 

A special group of 8-lactones formally derived from the hydrox-ycinnamic acids are coumarins with a skeleton of 2//-benzopyran-2-one, which is also called chromen-2-one or 5,6-benzo-2-pyrone (8-99). More than 1000 coumarins are found in nature, but only the basic member of the homologous series of coumarins performs as an aromatic compound this is called coumarin. Plant materials also contain a number of non-volatile coumarins substituted with hydroxyl and methoxyl groups and their glycosides. These and other coumarins, generally taking on the role of phytoalexins, such as iso-coumarins, furanocoumarins and pyranocoumarins, are described in Section 10.3.2.5.2. Some isocoumarins are intensely sweet (such as phyllodulcin) or bitter substances (such as 6-methoxymellein),... 

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. 

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

Data from f.a.b.-m.s., and also f.d.-m.s., revealed the existence of naturally occurring, large cyclic polysaccharides. The first indication that a molecule may be cyclic comes from its precise molecular-weight determination. Cyclic molecules are 18 mass units less than their linear counterparts. Loss of water may, of course, occur in a number of ways, for example, by dehydration or lactonization, and conclusive evidence for the presence of a cyclic molecule can only be obtained from f.a.b.-m.s. of suitable derivatives, such as the permethyl derivative. Cyclic and dehydrated linear polymers are distinguishable after permethylation, as the cyclic polymer will incorporate one methyl group less than the linear molecule. 

One of the best methods to synthesize cyclopentenone derivatives is the Pauson-Khand procedure. However, Shindo s group have recently developed a domino process consisting of a [2+2] cycloaddition of a ketone with anynolate, followed by a Dieckmann condensation to give a 3-lactone as 4-190 which is decarboxylated under reflux in toluene in the presence of silica gel to afford cyclopentenones [64a]. Thus, the reaction of 4-188 and 4-189 led to 4-190, which on heating furnished the linear cucumin 4-191 (Scheme 4.41). This natural product has been isolated from the mycelial cultures of the agaric Macrocystidia cucumis [65, 66]. The domino procedure described was also used to synthesize dihydrojasmone and a-cuparenone. Moreover, the [2+2] cycloaddition can be combined with a Michael reaction [64b]. 

Dianions derived from cyclic a-nitro ketones have been used for the preparation of the natural product phoracanthlide and related macrocyclic lactones (see Scheme 5.2).13 Alkylation of dianion of a-nitro cyclic ketones is followed by radical denitration with Bu3SnH (see Section... 

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