Y Lactones

By saccharic acid is usually meant D-gluco-saccharic acid, m.p. 125-126°C, obtained by the oxidation of glucose or starch. This exists in water solution in equilibrium with its two y lactones, both of which can be obtained crystalline, though the acid itself does not crystallize readily. 

As an example, let s analyse the synthesis of y-lactones (e.g. TM 334) and see how we may choose one of a number of strategies depending on the structure of the target molecule. We ll consider in turn each of the three C-C bond disconnections. The one with the most appeal is probably b complete the analysis for this approach. 

The y-lactone problem is made easier because the FGs are all based on oxygen. The molecule can therefore be disconnected without FGl except for oxidation or reduction. Let s now look at the synthesis of a molecule with a difficult FG the muscle relaxant baclofen TM 349. What is the difficult FG ... 

Analysis This is a y-lactone and we spent time considering possible strategies for these compounds in fi ames 334-348. First open the lactone ring. This gives us a compound with 1,4- 1,5- and 1,6-dioxygenation relationships. FU follow the 1,6 through. 

Epoxides provide another useful a -synthon. Nucleophilic ring opening with dianions of carboxylic acids (P.L. Creger, 1972) leads to y-hydroxy carboxylic acids or y-lactones. Addition of imidoester anions to epoxides yields y-hydroxyaldehyde derivatives after reduction (H.W. Adickes, 1969). 

The regioselectivity of the addition of terminal alkynes to epoxides is improved, when the reagents prepared from the lithiated alkynes and either trifluoroborane or chlorodiethyl-aluminum arc employed (M. Yamaguchi, 1983 S. Danishefsky, 1976). (Ethoxyethynyl)lithium-trifluoroborane (1 1) is a convenient reagent for converting epoxides to y-lactones (M. Naka-tsuka, 1990 see p. 327f. cf. S. Danishefsky, 1976). 

The reductive coupling of aldehydes or ketones with 01, -unsaturated carboxylic esters by > 2 mol samarium(II) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

The use of epoxides as alkylating agents for diethyl malonate provides a useful route to y lactones Wnte equations illustrating such a sequence for styrene oxide as the starting epoxide Is the lactone formed by this reaction 3 phenylbutanohde or is it 4 phenylbutanohde ... 

Rea.ctlons, Butyrolactone undergoes the reactions typical of y-lactones. Particularly characteristic are ring openings and reactions in which ring oxygen is replaced by another heteroatom. There is also marked reactivity of the hydrogen atoms alpha to the carbonyl group. 

Xyhtol also is obtained by sodium borohydride reduction of D-xylonic acid y-lactone (32) and from glucose by a series of transformations through diacetone glucose (46). 

Ascorbic Acid [50-81-1] (1) is the name recognized by the lUPAC-IUB Commission on Biochemical Nomenclature for Vitamin C (1). Other names are L-ascorbic acid, L-xyloascorbic acid, and L-// fi (9-hex-2-enoic acid y-lactone. The name... 

The most significant chemical characteristic of L-ascorbic acid (1) is its oxidation to dehydro-L-ascorbic acid (L-// fi (9-2,3-hexodiulosonic acid y-lactone) (3) (Fig. 1). Vitamin C is a redox system containing at least three substances L-ascorbic acid, monodehydro-L-ascorbic acid, and dehydro-L-ascorbic acid. Dehydro-L-ascorbic acid and the intermediate product of the oxidation, the monodehydro-L-ascorbic acid free radical (2), have antiscorbutic activity equal to L-ascorbic acid. 

This synthesis was the first step toward industrial vitamin production, which began in 1936. The synthetic product was shown to have the same biological activity as the natural substance. It is reversibly oxidized in the body to dehydro-L-ascorbic acid (3) (L-// fi (9-2,3-hexodiulosonic acid y-lactone), a potent antiscorbutic agent with hiU vitamin activity. In 1937, Haworth and Szent-Gyn rgyi received the Nobel Prize for their work on vitamin C. 

Chiral Alcohols and Lactones. HLAT) has been widely used for stereoselective oxidations of a variety of prochiral diols to lactones on a preparative scale. In most cases pro-(3) hydroxyl is oxidized irrespective of the substituents. The method is apphcable among others to tit-1,2-bis(hydroxymethyl) derivatives of cyclopropane, cyclobutane, cyclohexane, and cyclohexene. Resulting y-lactones are isolated in 68—90% yields and of 100% (164,165). 

The highest priority ring disconnective T-goals for 272 are those which disconnect a cocyclic 5,5-fusion bond and offexendo bond pair. The internal ketene-olefin cycloaddition in tactical combination with the Baeyer-Villiger transform is well suited to the double disconnection of such a cyclopentane-y-lactone ring pair. 

CHsjOH. CHlCgHg). CH(COOH). CH. COOH COOH. CHlCgHg). CH(CHaOH). CH. COOH COOH. CH(C2Hg). CH(COOH). CH. CH OH AomoPilopic acid is very stable, and is probably therefore the y-lactonic acid of one of these three hydroxy-acids. Further, pilopic acid seems to be produced from its higher homologue by loss of carbon dioxide and oxidation of the contiguous carbon atom. Of the four y-lactonic acids derivable from these three hydroxy-acids only two (I and II) answer these conditions,... 

Polyfluorinated a-diketones react with 1,2-diainino compounds, such as ortlio-phenylenediamine, to give 2,3-substituted quinoxalmes [103] Furthermore, the carboxyl function of trifluoropyruvates offers an additional electrophilic center. Cyclic products are obtained with binucleophiles [13, 104] With aliphatic or aromatic 1,2-diamines, six-memhered heterocycles are formed Anilines and phenols undergo C-alkylation with trifluoropyruvates in the ortho position followed by ring closure to form y-lactams and y-lactones [11, 13, 52, 53, 54] (equation 23). 

L-Ascorbic acid, better known as vitamin C, has the simplest chemical structure of all the vitamins (Figure 18.30). It is widely distributed in the animal and plant kingdoms, and only a few vertebrates—humans and other primates, guinea pigs, fruit-eating bats, certain birds, and some fish (rainbow trout, carp, and Coho salmon, for example)—are unable to synthesize it. In all these organisms, the inability to synthesize ascorbic acid stems from a lack of a liver enzyme, L-gulono-y-lactone oxidase. 

The potential 4-aroyl-2-hydroxy-3-aminofurans exist as y-lactones 178 (R = 6-aminouracil) (91JHC1501). 

Combined biotechnological and synthetic methods for preparation of polycyclic y-lactones, clinically important compounds 98PAC2093. 

Bioactive sesquiterpenic y-lactones and flavonoids in plants of Inula L. genus 97MI20. 

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