Lactone carbonyl group

In contrast to the saturated azlactones, the Friedel-Crafts reaction of 2-substituted-4-arylidene-5-oxazolones is quite complex and may follow several different courses, often concurrently, depending on both reaction conditions and structural variations in the arylidene ring. This behavior is readily interpreted in terms of the a,)S-unsaturated carbonyl moiety and the cross-conjugated system containing nitrogen, both of which provide potential reaction sites in addition to the lactone carbonyl group. The reaction has been investigated " ... 

The vanillin ethers 36 and 39 exhibited the IR band of the lactone carbonyl group at 1710-1720 cm whereas the aldehydic carbonyl stretching was observed in the range of 1680-1690 cm In the NMR spectra all the protons resonated at expected fields. The aldehydic proton appeared downfield around 9-10 aromatic protons in the range of 7-8 and the C3 - H of coumarin around 6.5. The methylene, methoxy, and methyl protons resonated around 5, 3.8, and 2.2, S respectively. 

Irreversible inhibition is probably due to the alkylation of a histidine residue.43 Chymotrypsin is selectively inactivated with no or poor inhibition of human leukocyte elastase (HLE) with a major difference the inactivation of HLE is transient.42,43 The calculated intrinsic reactivity of the coumarin derivatives, using a model of a nucleophilic reaction between the ligand and the methanol-water pair, indicates that the inhibitor potency cannot be explained solely by differences in the reactivity of the lactonic carbonyl group toward the nucleophilic attack 43 Studies on pyridyl esters of 6-(chloromethyl)-2-oxo-2//-1 -benzopyran-3-carboxylic acid (5 and 6, Fig. 11.5) and related structures having various substituents at the 6-position (7, Fig. 11.5) revealed that compounds 5 and 6 are powerful inhibitors of human leukocyte elastase and a-chymotrypsin thrombin is inhibited in some cases whereas trypsin is not inhibited.21... 

Reactions of acetal derivatives of aldonolactones involving the lactone carbonyl group or used as chiral precursors in the synthesis of noncarbohydrate natural products are discussed in later sections. 

The application of lithiumtrimethylsilyl acetate for the C-l elongation of aldonolactones has been examined (73). Although the reagent had been successfully used for the alkenation of lactone carbonyl groups (74), in the case of aldonolactones 10b or 25b only insignificant yields of the alkenes, but 30 - 40% of the lactols 49a or 50a, were obtained (73). However, these lactols, alternatively prepared in good yields by a Reformatsky-type reaction (53,54), were readily eliminated to the desired alkenes by simple treatment with methanesulfonyl chloride-triethylamine at 0°. Thus, from 49a or 50a separable E,Z mixtures (76a and 76b, or 77a and 77b, respectively) were obtained in good yields (73). 

Addition of alcohols to lactones results in the formation of orthoacid or orthoester derivatives. Thus, reaction of lactone 95a with potassium cyanide in ethanol led to displacement of the tosyl group by cyanide and addition of ethanol to the lactone carbonyl group, to give the orthoacid derivative 95b, which was isolated as its acetate 95c. Mild deacylation of 95c led back to 95b, but under more vigorous reaction conditions the open-chain methyl aldon-ate was obtained (90). 

When the benzoylated lactone 172a was debenzoylated with sodium methoxide and the product boiled in 1,4-dioxane, the more-stable 1,4-lactone 175 was isolated upon rebenzoylation. Reduction of the lactone carbonyl group afforded (220) the crystalline furanose derivative (176) of ascarylose. A similar procedure, performed on the benzoylated 3-deoxy-D-arabino-hexono-1,5-lactone 170, gave (221) the 3-deoxy-D-oraWno-hexo-furanose derivative. 

The mixed Claisen condensation ensures that only mono-alkylation of the lactone carbonyl group occurs. 

Cyclization with acid now causes a lot to happen. The 1,4-dicarbonyl compound cyclizes to a lactone, not to a furan, and the redundant ester group is lost by hydrolysis and decarboxylation. Notice that the double bond moves into conjugation with the lactone carbonyl group. Finally, the reduction gives the furan. No special precautions are necessary—as soon as the ester is partly reduced, it loses water to give the furan whose aromaticity prevents further reduction even with UA1H4. H... 

Lakhrissi, M, Chapleur, Y, Wittig olefination of lactone carbonyl groups, Angew. Chem. Int. Ed. Engl., 35, 750-752, 1996. 

One final example of acylation of alkynes by lactones forms part of the synthesis of neomethynolide by Yamaguchi. The Prelog-Djerassi lactone serves as the acylating agent (equation 49). The functionalized alkynide undergoes addition very selectively at the lactonic carbonyl group, despite the presence of a relatively unhindered primary ester. ... 

Recently, several papers have reported the isolation of new lactarane lactones, possessing the methyl group at C-3 either cis or trans to H-2, and the lactone carbonyl group either at C-5 (5-lactaranolides. Tables 11-13) or at C-13 (13-lactaranolides, Tables 16-17). Differentiation between these structural alternatives on the basis of spectroscopic data alone has been often risky, especially when only a single isomer is at hand. Therefore, chemical correlations, synthesis of the possible isomers, and molecular mechanics calculations have always been performed in order to corroborate spectroscopic informations. 

A special family of lactones, the coumarins, which widely occur in plants[84], have been investigated by NMR spectroscopy in some detail. Values for NMR chemical shifts for representative members of the class are shown as 64 and 65 data for dihydrocoumarin 63 is given to illustrate the influence of conjugation on the l o NMR signal for the lactone carbonyl group. 

Acid catalyzed reaction Dioxocarbenium ion activation of the lactone carbonyl group followed by attack of methanol (8 2 inversion) at the methyl-substituted y-carbon. 

Biosynthesis of hydrastine was followed by administering labeled dopamine 28-30), tyrosine 29-31), phenylalanine 29, 31) and methionine 32) to Hydrastis canadensis L. Two moles of tyrosine 30) but only 1 mole of dopamine were utilized 30). The lactone carbonyl group, the methylenedioxy group, and the N-methyl as well as the 0-methyl groups are derived from labeled formate and methionine 32). 

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