Divergent Synthesis of γ-Amino Acid and γ-Lactam Derivatives from meso-Glutaric Anhydrides

The first divergent synthesis of both γ-amino acid and γ-lactam derivatives from meso-glutaric anhydrides is described. The organocatalytic desymmetrisation with TMSN₃ relies on controlled generation of a nucleophilic ammonium azide species mediated by a polystyrene-bound base to promote efficient silylazidation. After Curtius rearrangement of the acyl azide intermediate to access the corresponding isocyanate, hydrolysis/alcoholysis provided uniformly high yields of γ-amino acids and their N-protected counterparts. The same intermediates were shown to undergo an unprecedented decarboxylation–cyclisation cascade in situ to provide synthetically useful yields of γ-lactam derivatives without using any further activating agents. Mechanistic insights invoke the intermediacy of an unconventional γ-N-carboxyanhydride (γ-NCA) in the latter process. Among the examples prepared using this transformation are 8 APIs/molecules of considerable medicinal interest.     

Stereoselective Synthesis of γ-(Acyloxy)carboxylic Acids and γ-Lactones Featuring the Switch of Stereopreference of Candida antarctica Lipase B in Sodium γ-Hydroxycarboxylate Homologues

Scalable protocols of straightforward synthesis of enantiomeric γ-(acyloxy)carboxylic acids and γ-lactones are presented. The key step is lipase-catalyzed stereoselective acylation of γ-hydroxycarboxylic acid sodium salt in organic solvent followed by acidification of the product, extraction and acidic relactonization of the unreacted enantiomer. The mixture of γ-(acyloxy)carboxylic acid and γ-lactone is separated either by extraction with solution of sodium bicarbonate or by distillation. A switch of enantioinduction of Candida antarctica lipase B along homologous nucleophiles from R configuration of γ-hydroxyhexanoic acid salt to S configuration of the C7 and longer-chain homologues has been disclosed. Both enantiomers of γ-(acyloxy)pentanoic acids; γ-(acetyloxy)octanoic and -nonanoic acids with S configuration; [(1S,5R)-5-(chloroacetyloxy)cyclopent-2-en-1-yl]acetic acid and enantiomeric γ-lactones derived from them were prepared with e. r. >98.5/1.5. The rates of acylation of C5 to C9 homologous salts differ by three orders of magnitude but remain applicable for preparative synthesis by variation of the enzyme loading and reaction time.     

Total synthesis of myceliothermophins A-E

Total synthesis of an antitumor compound myceliothermophin A and related compounds based on a convergent synthetic strategy was investigated. A common decalin skeleton of myceliothermophins was stereoselectively constructed by an IMDA reaction. The fully elaborated precursor of myceliothermophins was obtained via aldol reaction of N-protected γ-methoxylactam with decalin aldehyde. By using Teoc group for the protection of nitrogen atom of lactam ring, selective deprotection prior to the hydrolysis of methoxyaminal moiety was successfully achieved to obtain γ-methoxylactams (myceliothermophins C and D). Subsequent hydrolysis of these compounds afforded the corresponding γ-hydroxylactam, and myceliothermophins A and B in high yield. Myceliothermophin E was also synthesized by dehydration of the obtained γ-hydroxylactams. The absolute configurations of myceliothermophins A-E were also successfully determined.     

Cascade enantioselective synthesis of γ-aryl-γ-butyrolactones with a delayed stereoselective step

Enantioselective synthesis of γ-aryl-γ-butyrolactones is achieved using (S)-1-phenylethylamine as a chiral auxiliary. The synthesis involves cascade formation-destruction-formation of the chiral centre with a delayed stereoselective step. The actual stereoselective step has been found to be intramolecular nucleophilic attack on a diastereotopic carbocation formed, thereby resulting in the formation of non-racemic γ-aryl-γ-butyrolactones.     

A new umpolung for direct γ-regioselective nucleophilic addition of alcohols to γ-enolizable α,β-unsaturated aldehydes

A direct γ-regioselective nucleophilic addition of alcohols toward γ-enolizable α,β-unsaturated aldehydes was developed using a catalytic amount of MeSO₃H (30 mol%) and a stoichiometric amount of chloranil (1.0 equiv) as the oxidant. The addition of hexafluoroisopropanol (HFIP) was found to accelerate this cross-dehydrogenative coupling, furnishing diverse alcoholic adducts with high γ-regio- and E-stereoselectivities.     

Stereoselective syntheses of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones and naturally occurring lipid guggultetrol

γ-Oxo-butyramides derived from tartaric acid serve as excellent precursors for the synthesis of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones and for the synthesis of tetrols containing three contiguous stereogenic centres. The methodology presented here is general for the synthesis of γ-alkyl (aryl)-α,β-dihydroxy-γ-butyrolactones. Utility of the chiral building block was demonstrated by the synthesis of naturally occurring lipid guggultetrol.     

Gamma-Ray Irradiation to Accelerate Crystallization of Mesoporous Zeolites

Gamma-ray (γ-ray) irradiation was introduced into zeolite synthesis. The crystallization process of zeolite NaA, NaY, Silicalite-1, and ZSM-5 were greatly accelerated. The crystallization time of NaA zeolite was significantly decreased to 18 h under γ-ray irradiation at 20 °C, while more than 102 h was needed for the conventional process. Unexpectedly, more mesopores were created during this process, and thus the adsorption capacity of CO₂ increased by 6-fold compared to the NaA prepared without γ-ray irradiation. Solid experimental evidence and density function theory (DFT) calculations demonstrated that hydroxyl free radicals (OH*) generated by γ-rays accelerated the crystallization of zeolite NaA. Besides NaA, mesoporous ZSM-5 with MFI topology was also successfully synthesized under γ-ray irradiation, which possessed excellent catalytic performance for methanol conversion, suggesting the universality of this new synthetic strategy for various zeolites.     

New and efficient one-pot synthesis of functionalized γ-spirolactones mediated by vinyltriphenylphosphonium salts

The addition of dimethyl acetylenedicarboxylate to isatin derivatives in the presence of triphenylphosphine leading to new highly functionalized γ-spirolactones is reported.     

Synthesis of chlorinated β- and γ-lactones from unsaturated acids with sodium hypochlorite and Lewis acids

The direct synthesis of several β- and γ-lactones used as electrophilic sources of chlorine, sodium hypochlorite and a Lewis acid is described. The scope and limitations of the method are discussed.     

γ-Hydroxy-α,β-acetylenic esters: asymmetric syntheses and applications

γ-Hydroxy-α,β-acetylenic esters are versatile synthetic precursors to many organic compounds. This paper reviews the synthesis of chiral γ-hydroxy-α,β-acetylenic esters by asymmetric reduction of γ-oxo-α,β-acetylenic esters, enantioselective addition to aldehydes in the presence of chiral catalysts, and diastereoselective addition to chiral aldehydes. The preparation of racemic γ-hydroxy-α,β-acetylenic esters is also included. Examples are provided for the application of γ-hydroxy-α,β-acetylenic esters in organic synthesis.     

Effect of gamma-irradiation of ion imprinted polymer (IIP) particles for the preconcentrative separation of dysprosium from other selected lanthanides

The selectivity of zinc with respect to copper ions was improved by γ-irradiation of surface imprinted polymer particles. We have reported the preparation of dysprosium ion imprinted polymer (IIP) particles by covalent approach during molecular imprinting. This paper reports the results obtained after γ-irradiation of dysprosium IIP particles and their use in the preconcentration/separation of dysprosium from dilute aqueous solutions containing other selected lanthanides. Further, the characterisation of blank and dysprosium IIP particles was carried out either with and without irradiation by IR, thermogravimetric analysis (TGA), differential thermal analysis (DTA), XRD and surface area and pore size analysis techniques. The significant features observed in these experiments in the non-selectivity of blank polymer particles for dysprosium over other lanthanide ions and 35-180-fold enhancement in selectivity coefficients of irradiated dysprosium IIPs formed by covalent approach. In addition, the selectivity coefficients obtainable by γ-irradiated were compared with unirradiated dysprosium IIP particles and separation factors obtained by liquid-liquid extraction separation using di(2-ethyl hexyl) phosphoric acid as extractant.     

Preparation of γ,δ-unsaturated-β-ketoesters: Lewis acid-catalysed CH insertion of ethyl diazoacetate into α,β-unsaturated aldehydes

The synthesis of γ,δ-unsaturated-β-keto esters was achieved by the Lewis acid-catalysed direct CH insertion of an α-diazoester into various α,β-substituted-unsaturated aldehydes. CH insertion of ethyl diazoacetate into alkyl- and aryl-substituted α,β-unsaturated aldehydes was performed under mild conditions to afford the corresponding γ,δ-unsaturated-β-keto esters in moderate to high yields as a mixture of keto/enol tautomers.     

形貌可控γ-硫化锰纳米晶的制备及表征

在表面修饰剂聚乙烯吡咯烷酮(PVP)存在的条件下,使氯化锰和硫化钠发生反应,在76℃无水乙醇溶液中,制备出了亚稳态的-γMnS纳米晶.当反应的搅拌速度不同时,得到的产物分别呈球形和椭球形.采用X射线衍射(XRD)、透射电镜(TEM)、紫外吸收光谱分析(UV)、X射线光电子能谱(XPS)等手段对产物的形貌、结构和光学性质进行了表征,并据此推导了不同形貌纳米微粒的生长机理.     

Practical asymmetric synthesis of a novel γ-secretase inhibitor

An efficient route to γ-secretase inhibitor hydroxyl thiophene sulfonamide 1 is described. The approach contains nine steps with an overall yield of 8%. The synthesis highlights a diastereoselective methylation using Evans' oxazolidinone method and a chiral Strecker reaction via Davis' sulfonimine protocol.     

Asymmetric synthesis of γ-nitroesters by an organocatalytic one-pot strategy

An enantioselective synthesis of γ-nitroesters by a one-pot asymmetric Michael addition/oxidative esterification of α,β-unsaturated aldehydes is presented. The procedure is based on merging the enantioselective organocatalytic nitroalkane addition with an N-bromosuccinimide-based oxidation. The γ-nitroesters are obtained in good yields and enantioselectivities, and the method provides an attractive entry to optically active γ-aminoesters, 2-piperidones, and 2-pyrrolidones.     

2-Isopropylbenzimidazole and 2-methylbenzimidazole as bulky proton sources: Stereoselective protonation and application to the synthesis of γ- and δ-lactones

2-Isopropylbenzimidazole and 2-methylbenzimidazole have been found to be effective bulky proton sources for stereoselective protonation of chiral enolate anions. 2-Isopropylbenzimidazole worked in the stereoselective protonation of the Birch reduction of chiral α,β-unsaturated imides. On the other hand, 2-methylbenzimidazole was found to be the best protonation reagent in the isomerization reaction of α,β-unsaturated imide into β,γ-unsaturated imide. The Birch reduction using 2-isopropylbenzimidazole realized a concise and stereoselective synthesis of δ-lactone 14, a sex pheromone of Macrocentrus grandii, while the isomerization reaction using 2-methylbenzimidazole was employed in the highly stereoselective synthesis of the γ-lactone intermediate in the synthesis of depsipeptide antibiotics. These bulky proton sources would be powerful tools to achieve a concise synthesis of natural products.     

腐植酸作用下γ-六氯环己烷在冰相中的光转化

研究了腐植酸(HA)存在下冰相体系中γ-六氯环己烷(γ-HCH)的光转化规律.结果表明,HA浓度对γ-HCH的光转化率呈现低浓度促进而高浓度抑制的现象;盐离子浓度、NO_2~-及NO_3~-对γ-HCH的光转化率均有促进作用;低浓度Fe~(3+)对γ-HCH的光转化率有促进作用,当Fe~(3+)的浓度增大到50μmol/L时,呈现抑制效应;γ-HCH在不同p H值条件下光转化速率的大小顺序为碱性中性酸性.冰相中HA通过产生单线态氧(~1O_2)、羟基自由基(·OH)及三重激发态(HA*)加速γ-HCH的光转化.HA存在下γ-HCH的光转化产物主要是五氯环己烯、邻二氯苯和对二氯苯、一氯苯,光转化过程中~1O_2通过消耗中间产物间接加速了γ-HCH的光转化过程.     

Diastereoselective conjugate addition of organocuprates to N-[4-(Dibenzylaminobutenoyl)]oxazolidinone. Synthesis of chiral β-substituted γ-aminoacids

The first conjugate addition reaction of organocuprates to N-enoyl oxazolidinone where a γ-nitrogen atom is present into α,β-unsaturated system is described. The reaction gave syn-products in moderate yields and high diastereomeric ratios. The removal of chiral oxazolidinone moiety and N-deprotection of amino group furnished chiral β-substituted γ -amino acids.     

Enantioselective synthesis of chiral γ-aryl α-keto ester by copper-catalyzed 1,4-conjugate addition using D2-symmetric biphenyl phosphoramidite ligand

Cu-catalyzed enantioselective 1,4-conjugate addition of β,γ-unsaturated α-keto ester compound was carried out to afford chiral γ-substituted γ-aryl α-keto ester, which could be conveniently converted to the potential skeleton of new Pril drugs. Up to 81% ee and 99% yield were afforded for the 1,4-conjugate addition using D₂-symmetric biphenyl phosphoramidite ligand.     

Organo-catalyzed enantioselective synthesis of some β-silyl γ-alkyl γ-butyrolactones as intermediates for natural products

The enantioselective synthesis of some β-silyl γ-alkyl γ-butyrolactones has been achieved by an organo-catalyzed Michael addition of enolizable aldehydes onto a silylmethylene malonate followed by a silicon-facilitated Bayer–Villiger oxidation of the β-silyl aldehyde adducts as the key step. γ-Alkyl γ-butenolides were obtained from the β-silyl γ-alkyl γ-butyrolactones by Fleming–Tamao oxidation of the silyl group to a hydroxy group and subsequent elimination. These butenolides are the advanced intermediates of some natural products such as (+)-γ-caprolactone, (+)-methylenolactocine, and (?)-quercus lactone.