A-Acyl-y-lactones

Hydrogen chloride a-Oximino- from a-acyl-y-lactones s. 19,550... 

Some lactones serve as starting material. y-Phenylazo-y-valerolactone is thermally rearranged to a mixture of pyridazinones 20 and 21 in a ratio of 1.75 1. A complex mechanism is proposed. Pyridazines also result from hydrazines and substituted y-lactones - or -acyl-y-lactones, which react as 1,4-dicarbonyl compounds. y-Chloroketones react with substituted hydrazines to gives pyridazines or Af-aminopyrrolines, depending upon the hydrazine used. ° y-Chlorobutanal gives the corresponding 1,4,5,6-tetrahydropyridazine. ... 

Finally, the a-hydroxy-y-lactones could be obtained optically pure, by esterification with acetyllactyl chloride and the resulting acetyllactyl derivatives were separated. Recently, a kinetic resolution of the a-hydro) -y-lactones has been described by Shiina, using an asymmetric acyl-transfert catalyst ((R)-BTM) in the presence of an acetylating agent. 

Bacterial virulence in gram-negative bacteria is mediated by A-acyl homoserine lactones (39) in a complex pathway, and amines are candidate inhibitors (Scheme 10). However, amines are not very reactive towards y-lactones and this offered an opportunity to test whether thioureas could catalyse the process via their known role as agents capable of deploying their two NH groups to activate the C=0 group. In a model of... 

In an approach to FR182877, Sorensen and co-workers generated allenoate intermediate 289 from an ce-bromo-ce,/j-unsaturated lactone and effected an intramolecular acylation to afford a-alkylidene-/3-keto-y-lactone 290 as a single stereoisomer (Scheme 19.52) [61]. Evidence for the allenoate intermediate was established by the treatment of a-bromoenoate 291 with tBuLi, which afforded the cydized compound 292 as a single stereoisomer. Treatment of the isomeric bromoenoate of compound 291 also gave 292. Hence this demonstrated a stereoselective but not stereospecific process. 

One-electron oxidation systems can also generate radical species in non-chain processes. The manganese(III)-induced oxidation of C-H bonds of enolizable carbonyl compounds [74], which leads to the generation of electrophilic radicals, has found some applications in multicomponent reactions involving carbon monoxide. In the first transformation given in Scheme 6.49, a one-electron oxidation of ethyl acetoacetate by manganese triacetate, yields a radical, which then consecutively adds to 1-decene and CO to form an acyl radical [75]. The subsequent one-electron oxidation of an acyl radical to an acyl cation leads to a carboxylic acid. The formation of a y-lactone is due to the further oxidation of a carboxylic acid having an active C-H bond. As shown in the second equation, alkynes can also be used as substrates for similar three-component reactions, in which further oxidation is not observed [76]. 

Lin, Y.H., Xu, J.L., Hu, J., Wang, L.H., Ong, S.L., Leadbetter, J.R., Zhang, L.H. Acyl- homoserine lactone acylase from Ralstonia strain XJ12B represents a novel and potent class of quorum-quenching enzymes. Mol Microbiol 2003 47 849-860. 

Acyl halides and alkynes also give lactones upon reaction with Ni(CO)4 in an aqueous acetone medium. The result in this system is typically a 3,y-unsaturated lactone, formed together with some product derived from condensation with molecules of solvent (equation 18). Lactones are also formed in low yield as byproducts from the reactions of acylnickel carbonyl anions (derived from addition of RLi to Ni(CO)4) with terminal alkynes at -30 A single example of y-aminolactone formation is reported from 2-butyne, CO and diethylamine, catalyzed by (Et2NH)2NiBr2. ... 

Figure 1 P. aeruginosa QS system. Its mechanism, (a) Biosynthesis of acyl-homoserine lactone (AHL). Abbreviations SAM, 5-adenosyl methionine ACP, acyl carrier protein, (b) General chemical structure of AHL molecules, generally called autoinducer-1 (AI-1). (c) Chemical structure of V. fischeri AI-1. (d) Chemical structure of P. aeruginosa 3-oxo-C y-HSL and (e) C4-HSL. (f) Pseuodomonas quinolone signal, PQS.

Trimethylsiloxy cyanohydrins (9) derived from an a,3-unsaturatied aldehyde form ambident anions (9a) on deprotonation. The latter can react with electrophiles at the a-position as an acyl anion equivalent (at -78 C) or at the -y-position as a homoenolate equivalent (at 0 C). The lithium salt of (9) reacts exclusively at the a-position with aldehydes and ketones. The initial kinetic product (10) formed at -78 C undergoes an intramolecular 1,4-silyl rearrangement at higher temperature to give (11). Thus the initial kinetic product is trapped and only products resulting from a-attack are observed (see Scheme 11). The a-hydroxyenones (12), -y-lactones (13) and a-trimethylsiloxyenones (11) formed are useful precursors to cyclopentenones and the overall reaction sequence constitutes a three-carbon annelation procedure. 

The first step of the Stobbe condensation is the deprotonation of the succinate at the a-carbon to afford an ester enolate that in situ undergoes an aldol reaction with the carbonyl compound to form a 3-alkoxy ester intermediate. The following intramolecular acyl substitution gives rise to a y-lactone intermediate which undergoes ring-opening and concomittant double bond formation upon deprotonation by the alkoxide ion. Under certain conditions the lactone intermediate can be isolated. 

DCC-mediated condensation of hydroxy aldehyde 240 and acid 268 gave the aldehyde ester 269 (70%). An intramolecular olefination followed by chromatographic separation of the desired C-8 diastereomer led to the isolation of the 16-membered ring macrocycle 270 in 20% yield. Desilylation, oxidation, and cyclization then afforded a 47% yield of y-lactone 271. Acylation of the C-3 hydroxyl group was followed by reduction of the y-lactone and C-9 carbonyl. 

Schreiber s early efforts in this area were focused on libraries of compounds having structural features reminiscent of rigid, complex, stereochemically rich natural products. In a key early example, solid-phase split-pool synthesis was used to generate a combinatorial library of over two million complex, polycyclic compounds derived from shikimic acid [17]. A stereoselective tandem acylation-nitrone cycloaddition was used to generate 18 tetracyclic scaffolds, to which 30 alkynes were coupled using a Sonogashira reaction, 62 amines were coupled via y -lactone aminolysis, and 62 carboxylic acids were coupled by alcohol esterification (Fig. 9.1-3(c)). In addition, a portion of the solid supports were left unreacted at each of the last three steps to generate a skip codon that further increased the diversity of the library. 

Double carbonylation As a radical mediator in the carbonylation of 4-alkenyl iodides, BujGeH behaves differently from BUjSnH, because it is a slower hydrogen donor, giving the second acyl radical time to react with the cyclic ketone, which was formed in the first step. Instead of the keto aldehydes, fused y-lactones become the major products. 

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