Enantiomeric lactone

Oxidation of evermicose (122) with bromine yielded a mixture of y- and <5-lactones, which was directly acetylated. Refluxing the acetate in benzene solution in the presence ofp-toluenesulfonic acid gave (176) a mixture of the unsaturated lactones 131 and 132. In related work, Ganguly and Saksena (177) obtained an enonolactone by oxidation of D-nogalose with Jones reagent, followed by -elimination promoted by piperidine. Similarly, L-no-galose gave the enantiomeric lactone. 

Decarboxylation of pyruvic acid and its isomers, including the enol tautomers and enantiomeric lactone structures, has been investigated at the B3LYP/6-311+- -G(3df, 3pd) level.18 It has been found that a keto form with trans CmethyiCketoCacidOhydroxyi and cis CketoCacidOH, and with one methyl hydrogen in a synperiplanar position with respect to the keto oxygen, is the most stable. 

Chiral catalysts with structures related to rhodium(II) acetate should principally afford optically pure enantiomeric > -lactones from diazoacetates of type 21. As a matter of fact, Doyle et al. have obtained alkoxy-substituted y-lactones 22 in 85-90% ee (eq. (10)) upon using a Rh2X4-catalyst derived from chiral 2-pyrroli-dinones [18], Related results suggest that the catalyst has a rigid stereochemistry throughout the catalytic cycle [19], which conclusion had already been drawn for enantioselective cyclopropanation [20] (cf. Section 3.1.7). 

Bemis et al. (1992) investigated the difference of 60-fold between the hydrolysis of two acyl-chymotrypsin derivatives, following the reaction with enantiomeric lactones that leads to P-substituted p-phenylpropionic esters. The S-ester (kdifferent molecules are modeled. 

Helmchen ef /. [63] used S( —)-l-phenylethylamine (23) to form amides of racemic lactones, which were separated directly on a silica Lobar column using petroleum ether/ethyl acetate. The enantiomeric lactones were recovered using acid hydrolysis (1 M sulphuric acid at 80 °C overnight). 

An interesting example of the rearrangements discussed above is the formation of the enantiomeric lactone from a 7-bromo-7-deoxy-heptonolactone, which means that the configurations at all chiral centers were inverted. For example,when 7-bromo-2,3,7-trideoxy-D-arafcmo-heptono-l,4-lactone (11) was treated with strong potassium hydroxide, 2,3-dideoxy-L-arafef o-heptono-l,4-lactone (12) was formed and isolated as the crystalline peracetate in 47% yield [24]. In contrast, when 11 was treated with aqueous potassium carbonate, workup gave 2,3-dideoxy-D-arafcfno-heptono-l,4-lactone (13), i.e. retention of con-... 

In any form of analysis it is important to determine the integrity of the system and confirm that artefacts are not produced as a by-product of the analytical procedure. This is particularly important in enantiomeric analysis, where problems such as the degradation of lactone and furanon species in transfer lines has been reported (40). As chromatography unions, injectors, splitters, etc. become more stable and greater degrees of deactivation are possible, problems of this kind will hopefully be reduced. Some species, however, such as methyl butenol generated from natural emissions, still remain a problem, undergoing dehydration to yield isoprene on some GC columns. 

Isolated problems of racemization, rearrangement or dehydration should not overshadow the fact, however, that the range of species amenable to enantiomeric two-dimensional GC is very wide indeed, including not only terpenes and lactones. 

Enantiomeric distribution of y-lactone homologues from different apricot cultivars. Identification of dihydro-actinidiolide (co-eluted with y-Cl 1 on DB-1701)... 

Determination of enantiomeric distributionof the lactone flavour compounds of fruits... 

S. Nitz, H. Kollmannsberger, B. Weinreich and F. Drawert, Enantiomeric distr ibution and C/ C isotope ratio deter mination of -y-lactones appropriate methods for the differentiation between natural and non-natural flavours , 7. Chromatogr. 557 187-197 (1991). 

The adjacent iodine and lactone groupings in 16 constitute the structural prerequisite, or retron, for the iodolactonization transform.15 It was anticipated that the action of iodine on unsaturated carboxylic acid 17 would induce iodolactonization16 to give iodo-lactone 16. The cis C20-C21 double bond in 17 provides a convenient opportunity for molecular simplification. In the synthetic direction, a Wittig reaction17 between the nonstabilized phosphorous ylide derived from 19 and aldehyde 18 could result in the formation of cis alkene 17. Enantiomerically pure (/ )-citronellic acid (20) and (+)-/ -hydroxyisobutyric acid (11) are readily available sources of chirality that could be converted in a straightforward manner into optically active building blocks 18 and 19, respectively. 

Soon after the disclosure of the total synthesis of ( )-gingkolide B, (see ref. 8a) Corey reported a concise, enantioselective synthesis of tetracyclic lactone 23, see Corey, E. J. Gavai, A. V. Tetrahedron Lett. 1988, 29, 3201. Thus, in principle, gingkolide B could be synthesized in its naturally occurring enantiomeric form. 

The addition of the anion of ( + )-rm-butyl [(/J)-4-methylphenylsulfinyl]acetate to a,/ -unsatitrated esters gave 2,3-disubstituted 1-tm-butyl 5-ethyl 2-[(/ )-4-methylphenylsulfinyl]pentane-dioates which were converted to -substituted -lactones. The enantiomeric purities of the latter ranged from 0-24 %23. 

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

Thus, the lithiated SAMP hydrazones of various methyl ketones on addition to 2-(aryl-methylene)- , 3-propanedionates and propanedinitriles provide, after the removal of the auxiliary, (R)-2-( l-aryl-3-oxobutyl)-1,3-propanedioates and -propanedinitriles with high enantiomeric excess (> 95%) in 50 82% yield (sec Table 6) 195,197. Using similar methods optically active (5-lactones (90% to > 96% ee) are obtained198. 

The use of enantiomerically pure (R)-5-menthyloxy-2(5.//)-furanone results in lactone enolates, after the initial Michael addition, which can be quenched diastereoselectively trans with respect to the /J-substituent. With aldehydes as electrophiles adducts with four new stereogenic centers arc formed with full stereocontrol and the products are enantiomerically pure. Various optically active lactones, and after hydrolysis, amino acids and hydroxy acids can be synthesized in this way317. 

The addition of the lithium enolates of various acetic add esters to (S)-3-(4-methylphcnyl-sulfmyl)-2(5//)-liiranone and (,S)-5,6-dihydro-3-(4-methylphenylsulfinyl)-2//-pyran-2-one gives, after desulfurization with Raney nickel, 4-substituted dihydro-2(3//)-furanoncs and 4-substituted tetrahydro-2//-pyran-2-ones, respectively, in good to quantitative enantiomeric excess. Addition of the enolate occurs via the nonchelate mode. The enolate of methyl (phenylthio)acetatc is best overall in regards to chemical yields and enantiomeric purity of the final lactone product13. 

An intramolecular version of enolate Michael addition to enantiomerically pure vinylic sulfoxides is represented by reaction of a cyclopentenone sulfoxide with dichloroketene (Scheme 5)90 this type of additive Pummerer rearrangement has been developed by Marino and coworkers91 into a highly effective way of constructing variously substituted lactones in very high enantiomeric purity (equation 43). 

The initial results of an early directed evolution study are all the more significant, because no X-ray data or homology models were available then to serve as a possible guide [89]. In a model study using whole E. coU cells containing the CHMO from Adnetohacter sp. NCIM B9871,4-hydroxy-cydohexanone (3 5) was used as the substrate. The WT leads to the preferential formation of the primary product (i )-36, which spontaneously rearranges to the thermodynamically more stable lactone (R)-37. The enantiomeric excess of this desymmetrization is only 9%, and the sense of enantioselectivity (R) is opposite to the usually observed (S)-preference displayed by simple 4-alkyl-substituted cydohexanone derivatives (see Scheme 2.10) [84—87]. 

A related situation is found in the case of P-substituted cycloketones here, the electronic difference between the two a-carbons is almost insignificant, resulting in unselective migration upon chemical oxidation. BVMOs have a particularly different behavior, as they can influence the stereo- and/or regioselectivity of the biooxidation. In the latter case, the distribution of proximal and distal lactones is affected by directing the oxygen insertion process either into the bond close or remote to the position of the P-substituent. Consequently, a regioisomeric excess (re) can be defined for this biotransformation, similar to enantiomeric excess or diastereomeric excess values [143]. 

Jorgensen et al. [84] studied how solvent effects could influence the course of Diels-Alder reactions catalyzed by copper(II)-bisoxazoline. They assumed that the use of polar solvents (generally nitroalkanes) improved the activity and selectivity of the cationic copper-Lewis acid used in the hetero Diels-Alder reaction of alkylglyoxylates with dienes (Scheme 31, reaction 1). The explanation, close to that given by Evans regarding the crucial role of the counterion, is a stabilization of the dissociated ion, leading to a more defined complex conformation. They also used this reaction for the synthesis of a precursor for highly valuable sesquiterpene lactones with an enantiomeric excess superior to 99%. 

Lipase catalysis is often used for enantioselective production of chiral compounds. Lipase induced the enantioselective ring-opening polymerization of racemic lactones. In the lipase-catalyzed polymerization of racemic (3-BL, the enantioselec-tivity was low an enantioselective polymerization of (3-BL occurred by using thermophilic lipase to give (/ )-enriched PHB with 20-37% enantiomeric excess (ee). ... 

Cells of Acinetobacter sp. NCIB 9871 grown with cyclohexanol carried out enantiomeri-cally specific degradation of 5-bromo-7-fluoronorbornanone and production of a lactone with >95% enantiomeric excess (Levitt et al. 1990). 

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