Correlation lactones

The SECSY spectrum of the coumarin presents cross-peaks for various coupled nuclei. These cross-peaks appear on diagonal lines that are parallel to one another. By reading the chemical shifts at such connected cross-peaks we arrive at the chemical shifts of the coupled nuclei. For instance, cross-peaks A and A exhibit connectivity between the vinylic C-4 and C-3 protons resonating at 8 7.8 and 6.2, respectively. The C-4 methine appears downfield due to its )3-disposition to the lactone carbonyl. Similarly, cross-peaks B and B show vicinal coupling between the C-5 and C-6 methine protons (8 7.6 and 7.1, respectively) of the aromatic moiety. The signals C and C represent the correlation between the oxygen-bearing C-11 (85.4) andC-12 (84.6) methine protons in the side chain. These interactions are presented around the structure. 

The stereochemistry of the enol lactones was established by correlation with the structure of derivative 121, prepared from bicuculline (88), whose configuration as Z was determined by X-ray analysis (95). In this correlation... 

In summary, reactions of nitronates with acid anhydrides or acyl chlorides give the O-acylated products, and reactions with acyl imidazoles, phenyl esters, acyl nitriles, and enol-lactones gives the C-acylated products, (see Eq. 5.13).25 The C/O selectivity of nitronate acylation by RCOX is qualitatively correlated with strength (pKJ of the acid HX conjugated to the leaving group X .25... 

There are distinct correlations between the mechanism of formation of compound 43, the eliminations frequently observed with derivatives of aldaric acids, and the reducing power of alkyl D-glucofuranosidurono- and l,2-0-alkylidene-a-D-glucofuranurono-6,3-lactones toward complexed copper(II) solutions. These phenomena are discussed in Section VII. 

V. Structure-Reactivity Correlations. Conformation of d-Glucofuranosidurono-6,3-lactones... 

When pyridinium salt 187 was transformed to an indolo[2,3-a]quinolizidine compound in a similar way and the unsaturated lactone 188 was hydrogenated over platina catalyst, a mixture of vallesiachotamine-type compounds (189 di-astereomers) epimeric at C-20 was formed (134). These compounds have also been prepared in optically active form from vallesiachotamine (9), thus producing the first chemical correlation between synthetic and natural vallesiachotamine derivatives (134). 

Dunitz, in his review (82), describes also studies on other systems. It should be mentioned that in the O - - C=0 interaction the correlation is poorer than inN C=0, presumably because the interaction is weaker and more sensitive to perturbation. However, compounds 39 and 40 of this series are worthy of note. The keto acid 39a and the isomeric lactone alcohol 39b are in dynamic equilibrium in solution at room temperature, and are present in similar concentrations. This substance has been obtained in only one crystal modification, corresponding to die closed form, 39b. However, the pattern of bond lengths... 

Hwang D, Fischer NH, Jang BC, Tak H, Kim JK, Lee W. (1996). Inhibition of the expression of inducible cyclooxygenase and proinflammatory cytokines by sesquiterpene lactones in macrophages correlates with the inhibition of MAP kinases. Biochem Biophys Res Common. 226(3) 810-18. 

Quantitative analysis of feverfew with regards to sesquiterpene lactone content has been carried out by TLC [72,73] and HPLC [71,74,75] and H-NMR spectroscopy [75]. Measurements of parthenolide by HPLC correlated well with measurements by bioassays based on 5HT-secretion from platelets [75]. The availability of several techniques for quantitation of parthenolide levels in feverfew, makes some standardization of commercial preparations possible. 

The position of the functional groups along the eremophilane core was confirmed by an HMBC experiment. In particular, the correlations C-lO/OH-1, H-6, H-9 C-8/H-9, H-6, H-13 C-2/OH-1, H-4 and C-12/H-13 were consistent with the disposition of the ketone, hydroxyl and lactone functionalities. 

Clerodanes.—In a study of South African Macowania species, a cis-clerodane acid (28) and labdanolic acid were obtained from M. glandulosa. Deoxymarrubialac-tone (29) has been isolated from Chaiturus marrubiastrum. Linarienone (30) is another ds-fused clerodane which has been obtained from the roots of Linaria japonica (Scrophulariaceae) and correlated with linaridial. The bacchotricuneatins A (31) and B (32) are two new diterpenoid lactones which were isolated from Baccharis tricuneata (Astereae) and whose structures were determined by a combination of spectra and X-ray analysis. 

Related to case is reduction of the monoester (l/ ,25)-2-methoxycarbonyl-4-oxo-l-cy-clopentanecarboxylate (see p401) followed by lactone formation to give 36 and oxidation to the known bicyclic dione 3757. Configurational assignment rests on the fact that the ester group in 35 is reduced under the reaction conditions whereas the free acid is not. Thus, reliability in correlations of this type rests on a sufficient difference in reactivity of the two functional groups under the selected conditions. 

In toluene with 4 equiv methanol and a catalytic amount of the alkaloid. b ee values are determined by conversion of the monoesters to the (R)-l-(l-naphthalenyl)ethylamides (entries 1-14) and analysis by HPLC, by salt formation with (R)-l-phenylethylamine (entries 15-20) or by H-NMR spectroscopy in the presence of Eu(hfc)3. Absolute configurations are determined by chemical correlation or by X-ray analysis of the Mosher ester of the lactone alcohol (entry 21). With 20 equiv of methanol. d With 4 equiv of methanol. With 10 equiv of methanol. f With 3 equiv of methanol. 

A different approach to enantiotopic group differentiation in bicyclic anhydrides consists of their two-step conversion, first with (/ )-2-amino-2-phcnylethanol to chiral imides 3, then by diastereoselective reduction with sodium bis(2-methoxyethoxy)aluminum hydride (Red-Al) to the corresponding chiral hydroxy lactames 4, which may be converted to the corresponding lactones 5 via reduction with sodium borohydride and cyclization of the hydroxyalkyl amides 101 The overall yield is good and the enantioselectivity ranges from moderate to good. Absolute configurations of the lactones are based on chemical correlation. 

Enantioselective reduction of prostereogenic anhydrides la-g with 4 equivalents of chiral reducing reagent, obtained from lithium aluminum hydride, enantiomerically pure (M)-, 1 -bi-2-naph-thol and ethanol, provides easier access to chiral lactones as exemplified by 3a-g.10 la. Absolute configurations of lactones 3 are based on chemical correlation and the ee value for 3b is determined by HPLC on the chiral column Chiralcel OB-H (Daicel Chemical Industries, Ltd.)101b. 

The mechanism of decarboxylation of /3-lactones has attracted much attention. The gas-phase decomposition of 2-oxetanone is a unimolecular first-order process. It has a considerably lower energy of activation than the pyrolysis of oxetane and a much higher entropy of activation, indicating a loose activated complex (69JA7743). The ease of the reaction is greatly affected by the electronic effect of substituents at position-4, but not at position-3. The Hammett treatment of a series of rrans-4-aryl-3-methyl-2-oxetanones gave a good correlation with [Pg.374]

Reaction with ammonia and primary and secondary amines can also give two types of products, 0-hydroxyamides or amino acids (equation 49). The amide is obtained from the reaction of 0-propiolactone with ammonia in water, while the amino acid is obtained from the reaction in acetonitrile, both in good yield. 0-Lactones react very generally with both aliphatic and aromatic amines, but the type of product does not correlate with polarity of solvent or basicity of amine. Fortunately, conditions can usually be found for the formation of the desired product. 

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