Cyclic lactones

The proposed mechanism for the conversion of the furanone 118 to the spiro-cyclic lactones 119 and 120 involves electron transfer to the a -unsaturated methyl ester electrophore to generate an anion radical 118 which cyclizes on the /3-carbon of the furanone. The resulting radical anion 121 acquires a proton, giving rise to the neutral radical 122, which undergoes successive electron transfer and protonation to afford the lactones 119 and 120 (Scheme 38) (91T383). 

Substituted Cyclic Lactones by Condensation of ( + )-(/f)-3-(4-methylphenylsulfinyl)propanoic Acid with Carbonyl Compounds General Procedure46 ... 

The studies described above show that a quinone methide or its aza-analogue quinonimine methide incorporated as a latent electrophilic species into a cyclic lactone or lactam precursor can modify a second nucleophilic residue within the enzyme active site after formation of the acyl-enzyme. Very efficient suicide... 

Serajuddin et al. [19] reported that the degradation pathway of prevastatin sodium was directly linked to the micro-pH environment within the formulation. Under neutral conditions (pH 6.5), the statin formed two degradation products, a cyclic lactone and an internal hydroxyl rearrangement product. However, as the pH was increased to 9.9 with the incorporation of magnesium oxide into the blend, the only degradation mechanism involved the formation of the cleavage product, 2-methylpropanoic acid. This latter approach of increasing the... 

Lactonization of the suitable hydroxy acids or their derivatives is the most common synthetic method for benzoxepinenones with fused pyrrole rings. Therefore, reduction of the formyl group in the ester aldehyde 121 with sodium borohydride gives a mixture of alcohol 122 (80% yield) and lactone 123 (19%). Further heating of the open-chain product 122 in refluxing ethanol affords cyclic lactone 123 quantitatively (Scheme 25 (1998T11079)). 

Cyclic lactone 125 has been observed as the only minor product of reduction of ketone 124 under thermal conditions. Stepwise reaction under mild conditions... 

Each desired enantiomer of 3-substituted dihydro-2(3.//)-furanones and 3-substituted tetrahydro-2//-pyran-2-ones was prepared starting either from 4,5-dihydro-2-(m-trimethylsilyloxy)oxazoles and alkylating with the corresponding alkyl halide, or by reversing the order of alkyl group introduction. Upon hydrolysis with dilute hydrochloric or sulfuric acid, 2-substituted cyclic lactones were obtained in 40-75% overall yield and 60-86% enantiomeric excess20. 

Included in this group are avermectins and milbemycins, which are fermentation products possessing a 16-member cyclic lactone, a spirochetal moiety, and a disaccharide unit. Abamycin, ivermectin, doramectin, and eprinomectin are major avermectins available for anthelminthic treatment of livestock, whereas moxidectin is a milbemycin with worldwide acclaim as a cattle anthelminthic (Fig. 4.7). 

The reaction of sulfur tetrafluoride with 4-oxocarboxylic acids proceeds via cyclic lactones to give pentafluoroalkanes as the final product. The intermediate lactones may be isolated from reactions conducted under sufficiently mild conditions, e.g. formation of 27 via lactone 26.117... 

The thermal decomposition of ketene1>60 93 142 146 apparently does not occur by the simple unimolecular decomposition CH2CO CH2 + CO. Young146 suggests that CH2 actually results from breakdown of allene, which is an intermediate product. Ketene is known to dimerize readily, even in the gas phase on Pyrex surfaces to form the d-methylene cyclic lactone. 

Other ring contractions that give azapentalene derivatives include the rearrangement of a fused oxazine to a pyrazolo[l,5-a]indol-4-one with acetic anhydride,165 and an interesting photochemical contraction of a cyclic lactone, which produces an isomeric fused indolone by a mechanism thought to involve the first meta photo-Fries rearrangement [Eq. (19)].166 The product was used as an intermediate for the synthesis of mitomycin antibiotics (Section VI,A). 

C02 as a feedstock for organic substances will continue to be in the production of urea, carboxylic acids, and organic carbonates. On the other hand, many laboratory syntheses of organic substances derived from C02 have been published, ranging from hydrocarbons to cyclic lactones. These have recently been surveyed by Denise and Sneeden (S). 

Transition metal complexes have proved very useful in both the catalytic and stoichiometric production of cyclic lactones. A series of palladium(O)-phosphine complexes have been shown to be effective for the conversion of three-membered ring systems to cyclic lactones [Eq. (45)] (114). When isopropylidenecyclopropane and [Pd(dba)2]-PPh3 (dba = dibenzylidenea-cetone)(4 1) in benzene were treated with 40 atm carbon dioxide at 126°C for 20 hr, 69% of the lactone (34) was formed. In contrast, when [Pd(diphos)2] was used as the substrate under similar conditions 48% of 35 was produced with only trace amounts of 34. None of the complexes appeared to be active for terminal alkenes such as 36 or 37. 

The siderophore enterobactin (enterochelin) (64) is a cyclic lactone of three N-(2,3-dihydroxybenzoyl) L-serine moieties produced by E. coli under iron stress. Enterobactin (64) was first isolated from iron-limited cultures of Salmonella typhimur-ium [83], E. coli [84], and Aerobacter aerogenes [84]. Structural analysis has confirmed that 64 chelates iron as a hexadentate ligand via the two hydroxyl groups on each catechol moiety (see Fig. 13) [85]. Of all the siderophores characterized to date, 64 has been shown to have the highest affinity for ferric iron, with a stability constant of 1052 M 1 [86, 87], which is remarkable, considering the affinity of EDTA for iron is 27 orders of magnitude lower. In mammals, serum albumin [88] and siderocalin [89, 90] bind the hydrophobic 64 which impedes siderophore-mediated transfer of iron to bacteria. Consequently, bacteria such as E. coli and... 

Bachmann and Seebach [159] have reported the preparation and characterization of cyclic lactones (MeCHCH2C(0)0)n, where n = 4 and 8. The reaction product between butyl lithium in benzene and the solid polystyrene support PS-C6H4CH2NH2 leads to a lithiated species that can be represented as PS-Cfd bCI 12N11 Li(BuI i)x, where x 4 is active in the ring-opening of the cyclic esters L-lactide, rac-lactide, and 2,5-morpholinediones, leading to their respective cyclic oligoesters and cyclodepsipeptides (Fig. 49) [160]. The... 

GR133487 (5,5-rra/is-fused cyclic lactone euphane triterpene) Lantana camara (Verbenaceae) a-Chymotrypsin (10 nM), Factor Xla (1 pM), Plasmin (6 pM), a-Thrombin (4 nM), Trypsin (120 nM) [112]... 

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