The mechanism of the α-ketoacid-hydroxylamine amide-forming ligation

Three-ring circus! Surprisingly complex molecular acrobatics are observed in the mechanism of the α-ketoacid-hydroxylamine amide-forming ligation reaction. Although this remarkable reaction can already be used for the chemoselective union of large, unprotected peptide fragments the elucidated mechanism provides important clues to extending its application to larger and more complex biological targets.     

Synthesis of α-Phenylsulfonyl cyclopentanones by intramolecular carbenoid cyclization of α-Diazo-β-keto phenylsulfones

Acyclic α-diazo-β-keto phenylsulfones undergo smooth intramolecular carbenoid cyclizations under rhodium (II) catalysis to afford α-phenyl sulfonyl cyclopentanones.     

Catalytic α-allylation of unprotected amino acid esters

Catalytic α-allylation of unprotected amino acid esters to produce α-quaternary α-allyl amino acid esters is reported. Catalytic loadings of picolinaldehyde and Ni(II) salts induce preferential reactivity at the enolizable α-carbon of amino acid esters over the free nitrogen with electrophilic palladium π-allyl complexes. Fourteen examples are given. Additionally, the use of chiral ligands to access enantioenriched α-quaternary amino acid esters from racemic precursors is demonstrated by the enantioselective synthesis of α-allyl phenylalanine methyl ester from racemic phenylalanine methyl ester.     

Chemoselective Bromodecarboxylation of α-Carboxy- α-cinnamoyl Ketene Cyclic Dithioacetals

α-Oxoketene dithioacetals（ compound 1 ） are versatile synthons for organic synthesis due to their specially structural characteristic, that is, the masked ketene is conjugated with the convertible carbonyl in their molecules. Although there have been numerous reports covering the reactions in which they have been taken as 1,3-electrophiles, the reaction at the α-carbon atom of α-oxoketene dithioacetals has seldom been investigated. Junjappa and co-workers found the α- bromination of compound 2 in the presence of NBS led to α-aroyl-α-bromo ketenedithioacetals. However, the flexibility of the functional groups at the α-carbon atom of compound 2 are still limited.     

Ru/C catalyzed cyclization of linear α,ω-diamines to cyclic amines in water

A facile and convenient way to prepare cyclic amines in water was achieved by the catalyst system composed of Ru/C and Al powder. The α,ω-diaminoalkanes, 1,4-diaminobutane, 1,5-diaminopentane, and 1,6-diamino-heptane were converted to corresponding cyclic amines in good yields. The use of D₂O provided a novel route to obtain deuterated cyclic amines in good yields.     

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.     

Convenient green preparation of dipeptides using unprotected α-amino acids

Dipeptides and amides were obtained in high yields from N-carbobenzyloxy α-amino acids and 3-phenylpropanoic acid with unprotected α-amino acids via the corresponding mixed carbonic carboxylic anhydrides using ethyl chloroformate and triethylamine by an ecological and convenient method in which the protection of C-terminals is not needed.     

Enzymatic cyclization of linear peptide to plant cyclopeptide heterophyllin B

Cyclopeptide is an important family of natural products.Over the past decade,about100cyclopep-tides have been isolated from higher plants by our group[1].The biosynthesis of cyclopeptides from mi-crobes such as tyrocidine A has been reported re-cently[2-4…     

Supramolecular systems composed of α-helical peptides

Hydrophobic helical peptides having alternating hydrophobic amino acid and Aib in the sequence were synthesized to construct supramolecular systems. Three types of supramolecular systems were constructed by the peptides and the derivatives in different environments. First, the dispersion of TFA · H-(Ala-Aib)₈-OBzl in water was studied by dynamic light scattering, which suggests the formation of a vesicular structure with an average diameter of 76 nm. We call the peptide assembly in water “peptosome”. Second, Boc-Ser(Ant)-(Ala-Aib)₈-OMe spanned the phospholipid bilayer membrane and formed a helix-bundle structure. The bundle structure was supported by ion-channel formation in the membrane. Third, Boc-(Ala-Aib)₈-OMe and Boc-(Leu-Aib)₈-OBzl formed a two-dimensional crystal at the air-water interface. Boc-(Ala-Aib)₁₂-OBzl also formed a monolayer in a solid state at the air-water interface, but the helix orientation was perpendicular to the interface, which presents a contrast to the parallel orientation of the former hexadecapeptides.     

Synthesis of mutual azo prodrugs of anti-inflammatory agents and peptides facilitated by α-aminoisobutyric acid

Reported is the synthesis of azo mutual prodrugs of the nonsteroidal anti-inflammatory agents (NSAIDs) 4-aminophenylacetic acid (4-APAA) or 5-aminosalicylic acid (5-ASA) with peptides, including an antibiotic peptide temporin analogue modified at the amino terminal by an α-aminoisobutyric acid (Aib) residue. These prodrugs are designed for colonic delivery of two agents to treat infection and inflammation by the bacterial pathogen Clostridium difficile .     

Photoinduced radical reactions of α-alkylated ethyl 2-oxo-1-cyclopentanecarboxylate derivatives: α-cleavage and cyclization to the skeleton of linear cyclohexano diquinanes

The tricyclic core of linear cyclohexano diquinanes was synthesized using photoinduced electron transfer (PET) as a key step. The reaction proceeded in high regioselective manner via ketyl radical anions leading to distonic δ-keto radical anion as reactive intermediates. The irradiation was carried out at a wavelength of 254 nm with triethylamine (TEA) as a strong reducing reagent in acetonitrile. We also showed that the photolysis of the α-alkylated 2-oxocyclopentanecarboxylate derivatives does not lead to any cyclization products via a δ-hydrogen abstraction process. In this case α-C-C bond cleavage as a predominant process was observed.     

Construction of α-amido-indanones via formal allenamide hydroacylation-Nazarov cyclization

A two-step modular synthesis of an α-hydroxycyclopentenone and α-amido-indanones has been developed based on the Nazarov cyclization of 2-amido-1,4-pentadien-3-ones, readily accessed via formal hydroacylation of allenamides.     

Chemoselective Bromodecarboxylation of α-Carboxy-α-cinnamoyl Ketene Cyclic Dithioacetals

Introduction α-Oxoketene dithioacetals(compound 1) are versatile synthons for organic synthesis due to their specially structural characteristic, that is, the masked ketene is conjugated with the convertible carbonyl in their molecules[1-8].     

Chemoselective aromatic C-H insertion of α-diazo-β-ketoesters catalyzed by dirhodium(II) carboxylates

The ability of α-diazo-β-ketoesters bearing a substituent on the benzylic position to undergo aromatic C-H insertion is described. Good to excellent yields of the aromatic C-H insertion products were observed with Rh(2)(tpa)(4) or Rh(2)(esp)(2) catalysts. This is an attractive strategy to prepare tetralins carrying a methyl group on the benzylic position, a structural motif found in several types of natural products.     

Chemoselective conversion of α-unbranched aldehydes to amides, esters, and carboxylic acids by NHC-catalysis

Depending on the N-heterocyclic carbene catalyst utilized, α-unbranched aldehydes selectively provided amides, esters, or carboxylic acids through oxidation by NCS. The α-unbranched aldehyde underwent these reactions chemoselectively in the presence of an aromatic or α-branched aldehyde.     

Enantio-, Regio-, and Chemoselective Reduction of Aromatic α-Diketones by Baker’s Yeast

Summary. The enantio- and regioselective reduction of several symmetric and nonsymmetrically para-substituted benzil derivatives (21–92%) was achieved by means of Saccharomyces cerevisiae (bakers yeast). After modification of the reaction conditions reduction of nonsymmetric -diketones led chemoselectively to chiral -hydroxy ketones with up to 82% ee.Received December 16, 2002; accepted (revised) January 9, 2003 Published online July 28, 2003     

A Hydroperoxide-Mediated Decarboxylation of α-Ketoacids Enables the Chemoselective Acylation of Amines

Strategies for the formation of amide bonds, that is, one of the most basic and important transformations in organic synthesis, have so far focused predominantly on dehydration reactions. Herein, we report and demonstrate the practical utility of a novel decarboxylative amidation of α-ketoacids by using inexpensive tert-butyl hydroperoxide (TBHP), which is characterized by high yields, a broad substrate scope, mild reaction conditions, and a unique chemoselectivity. These features enable the synthesis of peptides from amino acid derived α-ketoacids under preservation of the stereochemical information.     

Synthesis of γ-benzopyranone by TfOH-promoted regioselective cyclization of o-alkynoylphenols

Regioselective cyclization of o-alkynoylphenols forming γ-benzopyranones has been demonstrated. Trifluoromethanesulfonic acid (TfOH) induced 6-endo cyclization of o-alkynoylphenols without forming 5-exo cyclized benzofuranone derivatives to provide the corresponding γ-benzopyranones in high yields.     

Enantioselective carbonyl-ene-type cyclization of α-ketoester and 2-substituted vinylsilane catalyzed by a chiral Cu-BOX complex

We developed an enantioselective carbonyl-ene-type cyclization using 2-substituted vinylsilane as a nucleophilic ene moiety catalyzed by a chiral copper-BOX complex. This reaction is the first example of enantioselective carbonyl-ene cyclization using a 1,2-disubstituted olefin. This methodology gave chiral indenols with a tetrasubstituted carbon.