A novel synthesis of α-hydroxy- and α,α′-dihydroxyketone from α-iodo and α,α′-diiodo ketone using photoirradiation

A novel reaction of α-iodo ketone (α-iodocycloalkanone, α-iodo-β-alkoxy ester, and α-iodoacyclicketone) with irradiation under a high-pressure mercury lamp gave the corresponding α-hydroxyketone in good yields. In the case of α,α′-diiodo ketone, α,α′-dihydroxyketone which little has been reported until now was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxy- and α,α′-dihydroxyketone.     

Microwave-assisted synthesis of α-hydroxy ketone and α-diketone and pyrazine derivatives from α-halo and α,α′-dibromo ketone

A novel reaction of α-halo ketone (α-bromo and α-chloro ketone) with irradiation under microwave gave the corresponding α-hydroxyketone and pyrazine derivative in good yields. In the case of α,α′-dibromo ketone, α-diketone was obtained. This reaction affords a new, clean and convenient synthetic method for α-hydroxyketone, α-diketone, α-chloro ketone and pyrazine derivative.     

Enantioselective synthesis of β,β-dialkyl α-hydroxy γ-butyrolactones

An ephedrine-derived morpholine dione is employed in the synthesis of chiral alkylidene morpholinones that are efficiently converted to β-substituted α,γ-dihydroxy butyramides, precursors of the corresponding butyrolactones. Enantioselective synthesis of a spiro analog of pantolactone as well as a naturally occurring pantolactone homolog is achieved with this protocol.     

High-performance liquid chromatographic method for the separation of the optical isomers of γ,γ′-di-tert.-butyl- -γ-carboxyglutamic acid and -γ-carboxyglutamic acid

The chemical synthesis of γ,γ′-tert.-butyl-γ-carboxyglutamic acid is accompanied by extensive racemization, and very careful resolution is needed to obtain and -γ,γ′-di-tert.-butyl-γ-carboxyglutamic acids in high chiral purity. A novel method was devised for the separation of enantiomers of γ,γ′-di-tert.-butyl-γ-carboxyglutamic acid and γ-carboxyglutamic acid, applying precolumn derivatization with 1-fluoro-2,4-dinitrophenyl-5- -alanine amide and 2,3,4,6-tetra-O-acetyl-β- -glucopyranosyl isothiocyanate as chiral reagents, with subsequent reversed-phase high-performance liquid chromatographic separation of diastereomeric compounds. The effects of organic modifiers, of the mobile-phase composition and of the pH on the separation of the diastereomers were investigated.     

Regioselective SN′ allylic substitution versus 1,4-addition: Synthesis of α-substituted β,γ-unsaturated esters

The reaction of the higher order organocuprate reagents R₂Cu(CN)Li₂-BF₃ with γ-bromo α,β-unsaturated esters gives with very high selectivity α-substituted β,γ-unsaturated esters arising from a SN′ allylic substitution. This reaction allows an easy access to α-silyl β,γ-unsaturated esters.     

Tandem epoxysilane rearrangement/Wittig-type reactions using γ-phosphinoyl- and γ-phosphonio-α,β-epoxysilane

Reaction of γ-phosphinoyl- and γ-phosphonio-α,β-epoxysilane with a base followed by addition of a ketone or an aldehyde afforded dienol silyl ether derivatives via a tandem process that involves base-induced ring opening of the epoxide, Brook rearrangement, and Wittig-type reaction.     

Synthesis of α,β-unsaturated ketone from α-iodo ketone using photoirradiation

Irradiation of α-iodo ketone in hexane under a nitrogen atmosphere with a high-pressure mercury lamp (λ>300nm) at room temperature afforded the corresponding α,β-unsaturated ketones in good yield. This reaction affords a new, clean and convenient synthetic method for the α,β-unsaturated ketone.     

Syntheses of methyl α-dl-mycaminoside, methyl α-dl-oleandroside, methyl β-dl-cymaroside, methyl α-dl-tyveloside and methyl α-dl-chromoside C

Five rare hexoses, which are components of antibiotics or cardiac glycosides, have been synthesized as methyl glycosides through a common intermediate methyl 2,3-dehydro-2,3,6-trideoxy-α-dl glucopyranoside (7). Epoxidation and subsequent treatment with dimethylamine of7 afforded methyl α-dl-mycaminoside (9). The addition reaction of MeOH to12 gave methyl α-dl-oleandroside (15) and methyl β-dl-cymaroside (17). The hydroxymercuration and subsequent reduction of12 afforded methyl α-dl-chromoside C (19) and methyl β-dl-tyveloside (25).     

Synthesis of novel α,α′,β-trisubstituted β-lactones

A concise and efficient synthesis of α,α′,β-trisubstituted β-lactones is presented. These novel lactones are easily obtained in five steps and will be dedicated to anionic ring opening polymerization.     

Lewis acid promoted aldol additions of α-thiosilylketeneacetals to α-alkoxy aldehydes: diastereoselective synthesis of -α-methylene-β-hydroxy-∂-alkoxy esters.

MgBr₂ mediated addition of Methyl α-methylthio propionate silylketene acetal to α and α,β-alkoxy aldehydes is highly 3,4 -selective (18:1). -α- methylene-β- hydroxy-∂-alkoxy esters (6) and (8) are synthesized.     

Photoinduced transformation of α,β-epoxyketones to β-hydroxyketones by Hantzsch 1,4-dihydropyridine

Irradiation (λ >300 nm) of Hantzsch 1,4-dihydropyridine with aromatic α,β-epoxyketones in acetonitrile selectively breaks the Cα---O bond of the epoxides giving the corresponding β-hydroxyketones in excellent yields.     

A novel ring contraction: 3β-methyl-A-nor-5β-cholestan-5-ol-6-one from 3β-tosyloxy-5α-cholestane-5,6β-diol through an ene reaction of an unsaturated acyloin

A by-product of the reaction of 3β-tosyloxy-5α-cholestane-5,6β-diol with , 3β-methyl-A-nor-5β-cholestan-5-ol-6-one, is believed to arise from the intramolecular ene reaction of 4,5-seco-cholest-3-en-6β-ol-5-one.     

Chlorination of α-sulfonyl carbanions with hexachloroethane: A novel preparation of α-halosulfones

The cyclic sulfones1,2, and3 are lithiated in benzene with n-butyllithium. Lithiation is demonstrated to lead to α-mono, α,α′-di and/or α,α-di and α,α,α′ trimetallation. The lithiated sulfones are chlorinated with hexachloroethane (HCE). Some mechanistic aspects of the reaction of the lithiosulfones with vicinal dihalides are discussed.     

The clemmensen reduction of α,β-unsaturated ketones

The deoxygenation of the α,β-unsaturated ketones (1) and (5) under the Clemmensen condition yielded the olefins (2) and (6) along with their respective dimers (3+4) and (8+9). The α , β-unsaturated ketone (13) under similar treatment yielded the olefin (14) in satisfactory yield but the dimer could not be characterized. The deoxygenation of the α,β-unsaturated ketones (10) and (16) under similar con- ditions afforded the olefins (12) and (15) respectively in satisfactory yield along with the rearranged olefins (11) and (17) respectively. Epox-idation of the olefin (17) followed by heating with p-toluenesulfonic acid yielded the ketone (18).     

A novel method for the synthesis of (Z)-α-selenyl-α,β-unsaturated ketones via acylation of (E)-α-selanylvinylstannanes

The (E)-α-selenylvinylstannanes react with acyl halides in presence of a catalytic amount of Pd(PPh₃)₄ to give the corresponding (Z)-α-selenyl-α,β-unsaturated ketones in good yield.     

Synthesis of α-phosphorylated cyclopentanones by intramolecularcarbenoid cyclizations of α-diazo β-keto alkylphosphonates and phosphine oxides

α-diazo β-ketoalkylphosphonates and phosphine oxides undergo intramolecular carbenoīd cyclizations under rhodium (II) catalysis to afford substituted diethoxyphosphono-2 and diphenylphosphono-2 cyclopentanones which, under Wittig-Horner conditions, lead to α-methylene cyclopentanones.     

Soy Isoflavones Inhibit Both GPIb-IX Signaling and αIIbβ3 Outside-In Signaling via 14-3-3ζ in Platelet

Soy diet is thought to help prevent cardiovascular diseases in humans. Isoflavone, which is abundant in soybean and other legumes, has been reported to possess antiplatelet activity and potential antithrombotic effect. Our study aims to elucidate the potential target of soy isoflavone in platelet. The anti-thrombosis formation effect of genistein and daidzein was evaluated in ex vivo perfusion chamber model under low (300 s⁻¹) and high (1800 s⁻¹) shear forces. The effect of genistein and daidzein on platelet aggregation and spreading was evaluated with platelets from both wildtype and GPIbα deficient mice. The interaction of these soy isoflavone with 14-3-3ζ was detected by surface plasmon resonance (SPR) and co-immunoprecipitation, and the effect of αIIbβ3-mediated outside-in signaling transduction was evaluated by western blot. We found both genistein and daidzein showed inhibitory effect on thrombosis formation in perfusion chamber, especially under high shear force (1800 s⁻¹). These soy isoflavone interact with 14-3-3ζ and inhibited both GPIb-IX and αIIbβ3-mediated platelet aggregation, integrin-mediated platelet spreading and outside-in signaling transduction. Our findings indicate that 14-3-3ζ is a novel target of genistein and daidzein. 14-3-3ζ, an adaptor protein that regulates both GPIb-IX and αIIbβ3-mediated platelet activation is involved in soy isoflavone mediated platelet inhibition.     

Additive Pummerer reactions of vinylic sulfoxides. Synthesis of γ-hydroxy-α,β-unsaturated esters, α-hydroxyketones, and 2-phenylsulfenyl aldehydes and primary alcohols

Treatment of β-monosubstituted vinylic sulfoxides 1 with trifluoroacetic anhydride in dichloromethane gave excellent yields of 1,2-bis(trifluoroacetoxy)thioethers 6. Mildly basic methanolysis of 2-alkyl-substituted 6 gave α-hydroxyaldehydes 11 as monomer-dimer mixtures; similar treatment of the 2-aryl analogues afforded aryl (hydroxymethyl) ketones 12. Compounds 11 underwent Wittig reactions with methoxycarbonylmethylenetriphenylphosphorane to give high yields of γ-hydroxy-α,β-unsaturated esters 13, predominantly as the E-isomers. β-Monosubstituted vinylic sulfoxides 1 possessing a β-aryl group, and β-disubstituted vinylic sulfoxides 3 reacted with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride to give 2-(phenylsulfenyl)acylals 14. These gave 2-phenylsulfenyl aldehydes 15 upon basic methanolysis, and the corresponding primary alcohols 16 on reduction with sodium borohydride. Reaction of both geometric isomers of enantiomerically pure vinylic sulfoxide 1o with TFAA gave racemic 6o as a mixture of diastereomers. Reaction of optically pure (E)- and (Z)-1p with trifluoromethanesulfonic anhydride-sodium acetate in acetic anhydride gave acylal 19 in 10.5 and 23% e.e., respectively.     

Diastereoselective SmI2-mediated cyclisation of δ-oxo-α,β-unsaturated esters to cyclopropanols

In the presence of samarium diiodide and a proton source, δ-oxo-γ,γ-disubstituted-α,β-unsaturated esters readily cyclise with complete diastereocontrol to give anti-cyclopropanol products.     

The Amyloid Fibril-Forming β-Sheet Regions of Amyloid β and α-Synuclein Preferentially Interact with the Molecular Chaperone 14-3-3ζ

14-3-3 proteins are abundant, intramolecular proteins that play a pivotal role in cellular signal transduction by interacting with phosphorylated ligands. In addition, they are molecular chaperones that prevent protein unfolding and aggregation under cellular stress conditions in a similar manner to the unrelated small heat-shock proteins. In vivo, amyloid β (Aβ) and α-synuclein (α-syn) form amyloid fibrils in Alzheimer’s and Parkinson’s diseases, respectively, a process that is intimately linked to the diseases’ progression. The 14-3-3ζ isoform potently inhibited in vitro fibril formation of the 40-amino acid form of Aβ (Aβ₄₀) but had little effect on α-syn aggregation. Solution-phase NMR spectroscopy of ¹⁵N-labeled Aβ₄₀ and A53T α-syn determined that unlabeled 14-3-3ζ interacted preferentially with hydrophobic regions of Aβ₄₀ (L11-H21 and G29-V40) and α-syn (V3-K10 and V40-K60). In both proteins, these regions adopt β-strands within the core of the amyloid fibrils prepared in vitro as well as those isolated from the inclusions of diseased individuals. The interaction with 14-3-3ζ is transient and occurs at the early stages of the fibrillar aggregation pathway to maintain the native, monomeric, and unfolded structure of Aβ₄₀ and α-syn. The N-terminal regions of α-syn interacting with 14-3-3ζ correspond with those that interact with other molecular chaperones as monitored by in-cell NMR spectroscopy.