Synthesis of stereodefined fused δ-hydroxy-γ-lactones from dealkylative cyclization of epoxy-diesters

A dealkylative lactonization of stereodefined aryl-substituted epoxides allows the preparation of densely functionalized fused δ-hydroxy-γ-lactones having three consecutive stereochemically defined stereocenters.     

The configuration of δ-lactones formed by cyclization of geranylacetic acid

Summary The previously proposed configurations for the -lactones formed by cyclization of the geranylacetic acids have been considered and exchanged.     

Diastereoselectivity in the directed aldol condensation of 2-trimethylsiloxyfuran with aldehydes. A stereodivergent route to threo and erythro δ-hydroxy-γ-lactones

Threo and erythro-δ-hydroxy-α,β-unsaturated γ-lactones are obtained with useful diastereoselection by condensing 2-trimethylsiloxyfuran and aldehydes by varying the reaction reaction conditions. A stereomechanistic rationale is presented together with a practical two-step synthesis of the threo and erythro 5-hydroxy-4-decanolides (L factors).     

A facile synthesis of bicyclic α-methylene-γ-lactones by intramolecular cyclization of allylsilylated aldehydes

Bicyclic α-methylene-γ-lactones were synthesized employing intramolecular reaction of an aldehyde unit with a β-ethoxycarbonylallylsilane function by the action of TiCl₄ in an excellent yield.     

A highly selective Bi(OTf)3 mediated fragmentation-contraction of δ-ortholactones. A facile route to functionalized γ-lactones

A very selective method for the formation of γ-lactones from pyranyl ortholactones has been developed which occurs via a fragmentation-acetate migration-ring contraction process. The reaction is very functional group tolerant, providing functionalized γ-lactones as a single isomeric product following the ring contraction. Mechanistic studies indicate the reaction is mediated by triflic acid liberated from Bi(OTf)₃ in a slow and controlled manner providing excellent chemo and regioselectivity. We propose the triflic acid acts as both a proton and a nucleophile source with triflate anion mediating the fragmentation process.     

Silylene transfer to α-keto esters and application to the synthesis of γ-lactones

Disubstituted α-hydroxy acids have been synthesized by metal-catalyzed silylene transfer to α-keto esters. A range of substituents are tolerated in the transformation with the exception of branched groups at the vinylic position. The α-hydroxy acid products can be converted into γ-lactones using a variety of lactonization conditions.     

Reductive aminopropylation of ketene silyl (thio)acetals leading to the synthesis of δ-amino esters

In the presence of silica gel or titanium tetrachloride, ketene silyl acetals or ketene silyl thioacetals underwent 1,4-addition with α,β unsaturated aldimines which possess a large triphenylmethyl group at the imino nitrogens followed by reduction with sodium cyanoborohydride to give aminopropylated products, δ-amino esters, in good yields.     

(R)-2,3-Cyclohexylideneglyceraldehyde, a novel template for stereoselective preparation of functionalized δ-lactones: synthesis of mosquito oviposition pheromone

(R)-2,3-Cyclohexylideneglyceraldehyde 1 has been used to prepare functionalized δ-lactones. This was exemplified by a simple and efficient synthesis of the oviposition pheromone 10 of Culex pipens fatigans.     

Cyclic structure of the β(γ)-hydroxy-(mercapto)alkylimines of aldoses

In solutions in DMSO-d₆, the products from the condensation of ethanolamine and 1,2- and 1,3-aminopropanols with aldoses are mixtures of the - and -pyranose forms, whereas the -mercaptoethylimines of aldoses have the 1,3-thiazolidine structure. Glucose -mercaptoethylimine is characterized by ring-chain tautomerism involving the -pyranose and diastereomeric 1,3-thiazolidine tautomers.Military-Medical Academy, St. Petersburg, Russia. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1068–1071, August, 1998.     

Synthesis of γ,γ-difluoro-β-hydroxy-δ-lactones as new precursors of HMG-CoA reductase inhibitor

A series of γ,γ-difluoro-β-hydroxy-δ-lactones 1 were efficiently synthesized as new precursors of HMG-CoA reductase inhibitor in one pot by treatment of readily prepared gem-difluoromethylenated acetonides 3 with trifluoroacetic acid. Contrarily, acetonides 3 could be transformed to the γ,γ-gem-difluoromethylenated α,β-unsaturated δ-lactones 2 through hydrolyzation and lactonization in refluxing toluene.     

Novel aziridination of α-halo ketones: an efficient nucleophile-induced cyclization of phosphoramidates to functionalized aziridines

A novel and efficient aziridination of α-halo ketones is reported. The reaction of α-halo ketones with diethyl N-arylphosphoramidates affords diethyl N-aryl-N-(2-oxoalkyl)phosphoramidates which undergo reductive (H⁻-induced) cyclization with sodium borohydride followed by sodium hydride to give 1,2-disubstituted and 1,2,3-trisubstituted aziridines. The cyclization induced by NCS⁻ or PhS⁻ affords substituted aziridines functionalized at C-2. The reactions give excellent yields and are highly diastereoselective in favour of cis aziridines.     

Tin(IV) chloride-chiral pyrogallol derivatives as new Lewis acid-assisted chiral Brønsted acids for enantioselective polyene cyclization

[reaction: see text] New Lewis acid-assisted Br?nsted acids (LBAs), tin(IV) chloride-2,6-dialkoxyphenols, serve as artificial cyclases for biomimetic polyene cyclization. For example, the enantioselective cyclization of 4-(homogeranyl)toluene using tin(IV) chloride-2,6-di[(1'R,2'R)-trans-2'-(3' ',5' '-xylyl)cyclohexanoxy]phenol gave a trans-fused tricyclic compound with 85% ee.     

γ-Lactones from δ-lactones: total synthesis of the biosynthetic derailment product mupirocin H

Two different strategies for the synthesis of functionalised γ-lactones from δ-lactones are described and used in a convergent synthesis of (+)-mupirocin H. The total synthesis is versatile and may be readily adapted for the preparation of further truncated metabolites from Pseudomonas fluorescens.     

1,3-Dipolar cycloaddition of a nitrone derived from (S)-malic acid to α,β-unsaturated δ-lactones

1,3-Dipolar cycloaddition of nitrone 7 to α,β-unsaturated δ-lactones: non-chiral 2, racemic mixture 3/3ent, d-glycero 3 and d-threo 15 proceeds with high stereoselectivity in the case of 2 and 15, and with a significant kinetic resolution in the case of the racemate 3/3ent. The endo approach of reactants was not observed. CD-spectroscopy proved an attractive tool for determination of the absolute configuration of cycloadducts.     

Binding energies of metal monocations to Β-lactones and Β-lactams. A theoretical study of cyclization effects

Ab initio calculations have been performed to study the association of-propiolactam and-propiolactone and their aliphatic analoguesN-methyl acetamide and methyl acetate with different metal monocations: Li⁺, Na⁺, Mg⁺, and Al⁺, in an effort to investigate cyclization effects on the gas-phase basicities of amides and esters, when the reference acid is not a proton. Similarly to what was found for protonation,N-methyl acetamide and-propiolactam are more basic than methyl acetate and-propiolactone, when the reference acids are the aforementioned metal monocations. However, cyclization effects on the corresponding binding energies for both kind of compounds do not parallel those observed for protonation energies, and-lactone is as basic as methyl acetate when the reference acid is Li⁺ and slightly more basic than methyl acetate when the attaching ion is Na⁺. This implies that when the interactions of the bases with the reference acids are essentially electrostatic the reactivity patterns change with respect to those observed when the interactions are essentially covalent.     

Synthesis of α-alkylidene-γ-lactones by intramolecular addition of alkoxycarbonyl free-radicals to acetylenes

α-Alkylidene-γ-lactones are obtained by treatment of chloroformate and selenocarbonate derivatives of homopropargylic alcohols with tri-n-butylstannane.     

Stereoselective synthesis of (±)-threo-γ-hydroxy-β-lysine lactone

A stereoselective synthesis of racemic threo-γ-hydroxy-β-lysine is reported. The threo aminoalcohol functionality is introduced by mercuric-ion initiated cyclofunctionalization of the acylaminomethyl ether 4a.     

Organocatalytic conjugate addition of α-nitroacetates to β,γ-unsaturated α-keto esters and subsequent decarboxylation: synthesis of optically active δ-nitro-α-keto esters

Organocatalytic asymmetric conjugate addition of tert-butyl nitroacetates to β,γ-unsaturated α-keto esters has been developed. The subsequent in situ hydrolysis-decarboxylation of the adducts provided 5-nitro-2-oxopentanoates. A pyrrolidine-based thiourea-tertiary amine was identified as the best catalyst. A number of γ-aryl, γ-alkyl, and γ-heteroaryl β,γ-unsaturated α-keto esters and α-substituted tert-butyl nitroacetates were examined in the transformation. Generally 5-nitro-2-oxopentanoates were obtained in good yields (up to 97%) and enantioselectivities (up to 94% ee). The products were readily transformed to chiral proline derivatives by catalytic hydrogenation.