A Novel Synthesis of γ,δ‐Unsaturated Aldehydes from α‐Formyl‐γ‐lactones

A preparatively useful one‐step transformation of γ,γ‐disubstituted α‐formyl‐γ‐lactones into trisubstituted γ,δ‐unsaturated aldehydes is described, by means of catalytic amounts of either AcOH or AcOEt in the vapor phase over a glass support. A mechanistic rationale is proposed.     

Peptide N‐Amination Supports β‐Sheet Conformations

The conformational heterogeneity of backbone N‐substituted peptides limits their ability to adopt stable secondary structures. Herein, we describe a practical synthesis of backbone aminated peptides that readily adopt β‐sheet folds. Data derived from model N‐amino peptides suggest that extended conformations are stabilized through cooperative steric, electrostatic, and hydrogen‐bonding interactions.     

Access to Cyclic β‐Amino Acids by Amine‐Catalyzed Enantioselective Addition of the γ‐Carbon Atoms of α,β‐Unsaturated Imines to Enals

Disclosed herein is a new catalytic approach for an efficient access to cyclic β‐amino acids widely found in bioactive small molecules and peptidic foldamers. Our method involves addition of the remote γ‐carbon atoms of α,β‐unsaturated imines to enals by iminium organic catalysis. This highly chemo‐ and stereo‐selective reaction affords cyclic β‐amino aldehydes that can be converted to amino acids bearing quaternary stereocenters with exceptional optical purities. Our study demonstrates the unique power of organic catalytic remote carbon reactions in rapid synthesis of functional molecules.     

A Mild Isomerization Reaction for β,γ‐Unsaturated Ketone to α,β‐Unsaturated Ketone

A series of β,γ‐unsaturated ketones were isomerized to their corresponding α,β‐unsaturated ketones by the introduction of DABCO in iPrOH at room temperature. The endo‐cyclic double bond (β,γ‐position) on ketone was rearranged to exo‐cyclic double bond (α,β‐position) under the reaction conditions.     

A rare occurrence of a β‐turn in an amyloid βA4 peptide

The fragment β(25–35) of the amyloid β‐peptide, like its parent βA4, has shown neurotrophic and late neurotoxic activities in cultured cells. The 3D structure of this important peptide was examined by ¹H and ¹³C 2D‐NMR and MD simulations in DMSO‐d₆ and water. The NMR parameters of chemical shift, ³J(N,Hα) coupling constants, temperature coefficients of NH chemical shifts and the pattern of intra and inter‐residue NOEs were used to deduce the structures. In DMSO‐d₆, the peptide was found to take up a type I β‐turn around the C‐terminal residues Ile⁸–Gly⁹–Leu¹⁰–Met¹¹, whereas in water at pH 5.5, it adopts a random coil conformation. This is only the second report of a β‐turn in the β‐amyloid class of peptides. The solution structures generated using restrained molecular dynamics were refined by MARDIGRAS to an R factor of 0.33 in the case of DMSO‐d₆ and to 0.56 for water. Copyright © 2002 John Wiley & Sons, Ltd.     

K21–δNa2+δIn39 (δ = 2.8): A Cluster-Replacement Clathrate-II Structure with an Alkali Metal M136-Network

K_21–δNa_2+δIn₃₉ with δ = 2.82 was synthesized (melted at 973 K, annealed at 623 K) from the elements in sealed niobium ampoules. The compound forms prismatic crystals with silver metallic lustre and is unstable in air and moisture. The crystal structure of K_21–δNa_2+δIn₃₉ (orthorhombic; space group Pnma, No. 62; a = 17.844(5) Å, b = 17.192(3) Å, c = 25.078(7) Å; Z = 4; Pearson code oP248; δ = 2.82, obtained from the structure refinement) contains eight empty In icosahedra of two types, A (12 exo-bonds) and B (7 exobonds), and four open In₁₅ clusters (15 exo-bonds). The latter are centered by K atoms and belong to C units, which are defined as [K(Na₂M₃In₁₅)] heteroatomic clusters (M = K + Na). The spatial distribution of the In icosahedra A, B and heteroatomic clusters C is that of the atoms in the cubic Laves phase MgCu₂: MgCu₂ ? [K(Na₂M₃In₁₅)][In]₂. All the In_n clusters are interconnected by exo-bonds forming a covalent three-dimensional framework (d(In? In) = 2.832 to 3.301 Å). The remaining alkali metal atoms build up a three-dimensional M₁₃₆ network of the clathrate-II type with (16 + 8) cages, which envelopes the In icosahedra and [K(Na₂M₃In₁₅)] clusters. This structure can be described as a cluster-replacement derivative of the clathrate-II structure: (H₂S)₁₆(CCl₄)₈ · (H₂O)₁₃₆ ? [In]₁₆[K(M₅In₁₅)]₈M₁₃₆, and is one member of a novel hierarchical structure family, based upon cluster-replacement. The bonding as well as the structural relationships to other phases are discussed.     

Controlling the Helix Handedness of ααβ‐Peptide Foldamers through Sequence Shifting

Peptide foldamers containing both cis ‐β‐aminocyclopentanecarboxylic acid and α‐amino acid residues combined in various sequence patterns (ααβ, αααβ, αβααβ, and ααβαααβ) were screened using CD and NMR spectroscopy for the tendency to form helices. ααβ‐Peptides were found to fold into an unprecedented and well‐defined 16/17/15/18/14/17‐helix. By extending the length of the sequence or shifting a fragment of the sequence from one terminus to another in ααβ‐peptides, the balance between left‐handed and right‐handed helix populations present in the solution can be controlled. Engineering of the peptide sequence could lead to compounds with either a strong propensity for the selected helix sense or a mixture of helical conformations of opposite senses.     

Comparison of Methionine α,γ‐Lyase and Homocysteine α,γ‐Lyase for Electrochemical Determination of Homocysteine

Recently, a novel enzymatic method was developed for determination of homocysteine. This method utilizes the electrochemical hydrogen sulfide sensor along with methionine α,γ‐lyase to accomplish the fast, accurate, sensitive and selective measurements. As a continuation of this work, another enzyme, homocysteine α,γ‐lyase, was used and the parallel experiments of using both enzymes were carried out against the effect of pH, sensitivity, linearity, and interferences, in an intended comparison between these two enzymes. The excellent linearity of amperometric currents against homocysteine concentrations, high sensitivities and low detection limits for both enzymes reconfirmed that the electrochemical method is superior over other analytical means. The high enzymatic activity of methionine α,γ‐lyase surpassing homocysteine α,γ‐lyase endowed the former higher sensitivity, lower detection limit and faster response than the latter, suggesting methionine α,γ‐lyase a better candidate for homocysteine measurement by electrochemical method. The differences between these two enzymes on the trends of response time and sensitivity at different pH environments, reactivity toward several forms of homocysteine as well as on the interference from several agents were also addressed and discussed.     

Enantioselective Syntheses of Substituted γ‐Butyrolactones

The previously described chiral 2‐acyloxathianes 5 (Scheme I) are used in two different enantioselective syntheses of γ‐butyrolactones. In one synthesis, Grignard addition, cleavage and reduction to carbinols RR'C(OH)CH₂OH is followed by tosylation, malonate homologation, lactonization, and removal of the carbomethoxy group to give optically active γ‐lactones. A modification of this synthesis (Scheme I) leads to optically active α‐methylene‐γ‐lactones. In the second synthesis, reaction of a bromomagnesium enolate with ketones 5 leads to β‐hydroxyesters, which, by appropriate sequences of reduction and cleavage (Scheme II) are converted to optically active α‐ or β‐hydroxy‐γ‐lactones.     

Aryloxide‐Facilitated Catalyst Turnover in Enantioselective α,β‐Unsaturated Acyl Ammonium Catalysis

A new general concept for α,β‐unsaturated acyl ammonium catalysis is reported that uses p‐nitrophenoxide release from an α,β‐unsaturated p‐nitrophenyl ester substrate to facilitate catalyst turnover. This method was used for the enantioselective isothiourea‐catalyzed Michael addition of nitroalkanes to α,β‐unsaturated p‐nitrophenyl esters in generally good yield and with excellent enantioselectivity (27 examples, up to 79 % yield, 99:1 er). Mechanistic studies identified rapid and reversible catalyst acylation by the α,β‐unsaturated p‐nitrophenyl ester, and a recently reported variable‐time normalization kinetic analysis method was used to delineate the complex reaction kinetics.     

Enantioselective NiH/Pmrox‐Catalyzed 1,2‐Reduction of α,β‐Unsaturated Ketones

The enantioselective 1,2‐reduction of α,β‐unsaturated ketones was achieved using a NiH catalyst in the presence of pinacolborane. This mild process represents a general method to access a wide variety of structurally diverse α‐chiral allylic alcohols in excellent yields and enantioselectivity, as well as very high levels of ambidoselectivity for 1,2‐ over 1,4‐reduction. Furthermore, for reactions on a 10 mmol scale, catalyst loadings as low as 0.5 mol % could be employed to deliver product without any detrimental effect on the yield, enantio‐, or ambidoselectivity.     

Reductive C−C Coupling from α,β‐Unsaturated Nitriles by Intercepting Keteniminates

We present an atom‐economic strategy to catalytically generate and intercept nitrile anion equivalents using hydrogen transfer catalysis. Addition of α,β‐unsaturated nitriles to a pincer‐based Ru?H complex affords structurally characterized κ‐N‐coordinated keteniminates by selective 1,4‐hydride transfer. When generated in situ under catalytic hydrogenation conditions, electrophilic addition to the keteniminate was achieved using anhydrides to provide α‐cyanoacetates in high yields. This work represents a new application of hydrogen transfer catalysis using α,β‐unsaturated nitriles for reductive C?C coupling reactions.     

Asymmetric and Geometry‐Selective α‐Alkenylation of α‐Amino Acids

Both E‐ and Z‐N′‐alkenyl urea derivatives of imidazolidinones may be formed selectively from enantiopure α‐amino acids. Generation of their enolate derivatives in the presence of K⁺ and [18]crown‐6 induces intramolecular migration of the alkenyl group from N′ to Cα with retention of double bond geometry. DFT calculations indicate a partially concerted substitution mechanism. Hydrolysis of the enantiopure products under acid conditions reveals quaternary α‐alkenyl amino acids with stereodivergent control of both absolute configuration and double bond geometry.