Stereoisomerism lactones

Figure 3.7 shows some early examples of this type of analysis (39), illustrating the GC determination of the stereoisomeric composition of lactones in (a) a fruit drink (where the ratio is racemic, and the lactone is added artificially) and (b) a yoghurt, where the non-racemic ratio indicates no adulteration. Technically, this separation was enabled on a short 10 m slightly polar primary column coupled to a chiral selective cyclodextrin secondary column. Both columns were independently temperature controlled and the transfer cut performed by using a Deans switch, with a backflush of the primary column following the heart-cut. 

A. Mosandl, U. Hener, U. Hagenauer-Hener and A. Kuster mann, Stereoisomeric flavor compounds. 33. Multidimensional gas chromatography dkect enantiomer separation of -y-lactones from fr uits, foods and beverages , 7. Agric. Food Chem. 38 767-771 (1990). 

H.-G. Schmarx, A. Mosandl and K. Grob, Stereoisomeric flavour compounds. XXXVIII dkect chir ospecific analysis of y-lactones using on-line coupled EC-GC with a chkal separation column , Chromatographia 29 125-130 (1990). 

The two meso forms, although optically inactive differ in chemical properties. For example, on heating the meso form A, readily forms a lactone, whereas the meso form B does not. In such an example the central carbon atom is said to be pseudoasymmetric. But if one of the carboxyl groups is esterified so that the top and bottom parts of the molecule become structually different, then the central carbon atom becomes truly asymmetric and the molecule would have three true asymmetric atoms and it will exist in eight stereoisomeric forms. 

When iodolactonization is carried out under nonbasic conditions, the addition step becomes reversible and the product is then the thermodynamically favored one.52 53 This usually results in the formation of the stereoisomeric lactone which has adjacent substituents Ira ns with respect to one another. 

A novel route to anthracyclinones is based on the chemistry of quinone-isobenzofuran adducts (77TL3537). The 3-methoxybenzyne-furan adduct (1) was reacted with a-pyrone to give a mixture of lactones (2). Thermolysis of this intermediate in the presence of quinone (3) gave in 93% yield the tetracyclic adduct (4) as a stereoisomeric mixture. Aromatization with sodium acetate in acetic acid gave quinone (5) which was subjected to reduction, C-ring oxidation and mild acid hydrolysis to afford a mixture of ( )-7-deoxydaunomycinone (6) and its 1-methoxy regioisomer (Scheme 1). 

The photoconversion of spiro[benzofuran-2,r-cyclohexa-3, 5 -diene]-2, 3(2//)-diones to dibenzofurans is recorded (81JCS(Pi)870). It was proposed that excitation of the dienone chromophore of the grisedienone (401) causes either concerted or radical ring opening to pairs of stereoisomeric dienylketenes. One member of each pair can undergo a thermal intramolecular va + tts cyclization to yield a /3-lactone subsequent loss of C02 would yield the products. 

Mosandl, A., Hener, U., Hagenauer-Hener, U., and Kustermann, A. 1989. Stereoisomeric flavor compounds. XXXII. Direct enantiomer separation of chiral y-lactones from food and beverages by multidimensional gas chromatography. J. HighResolut. Chromatogr. 12 532-536. 

This preparation is important in the sugar group, as it is possible to pass from one stereoisomeric acid to another by heating with pyridine— this enables the corresponding sugars to be transformed one into another by oxidation to the acid, transformation of the acid to its stereoisomer, and reduction of the lactone of the latter acid (see p. 190). 

It has been reported that reaction of n. 3-unsatu rated carboxylic acids with bis(collidine)bromine(l) hexafluorophos-phate leads to the formation of 2-oxetanones in moderate yields (Equation 33) <1999JOC81>. As with the related reaction of cinnamyl alcohols (discussed in Section 2.05.9.1), this 4- electrophilic intermediate. The cyclization reaction was diastereospecific single (E)- or (Z)-isomers were reacted to give single stereoisomeric products. Lactonization was favored by substrates that were /3-dialkyl-substituted, or ct-alkyl/aryl-, /3-aryl-substituted on the C-C double bond. ct-Monoalkyl/aryl, /3-unsubstituted substrates gave either polymeric products or exclusive vinyl bromide formation. 

McMurry and co-workers have reported that irradiation of the epimeric hydroxycy-clopentenones 37a, b yields the stereoisomeric lactones 38a, b most likely via an intermediate hydroxycyclopropyl ketene37. The stereospecificity of the reaction may result from hydrogen bonding between the hydroxyl group and the incipient carbonyl in the transition state. The results of quenching and sensitization experiments implicate a reactive singlet state. 

Reduction of 2,2-dimethyl-cyclohexane-1,3-dione (50) with Baker s yeast gave alcohol (ee 98.3%) whose tetrahydropyranyl derivative on methoxycarbonylation produced (51) quantitatively. Michael addition of (51) with methyl vinyl ketone followed by heating the adduct under reflux with pyrrolidine in benzene yielded (52) in 85% yield as stereoisomeric mixture whose separation presented problems. In order to eliminate the complexity due to a chiral center in tetrahydropyranyl protective group, deprotection of (52) was achieved by treatment with p-toluenesulphonic acid in methanol. The product obtained was a mixture of the lactone (53) and hydroxy ester (54). Probably the stereoisomer of... 

One of these stereoisomeric hydroxy acids readily forms a lactone upon heating, whereas the other does not. Explain these results. 

The enantioselective synthesis of phthalide 227 (the (3 )-isomer), and other substituted phthalides, and the determination of their absolute configuration has been reported <2005CH218>. In a different approach to the same compounds, 2-alkylbenzoic acids were fed to microorganisms known to affect asymmetric hydroxylation. Lactonization of the resulting alcohols yielded the phthalides, used as scents in cosmetics and soaps <1997JPP10243794>. There is sufficient interest in these optically pure compounds for a chiral gas chromatography (GC) stationary phase to have been developed to quantify stereoisomeric mixtures. A silylated /3-CD was employed... 

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