A simple approach for the synthesis of new pyrimidinyl α-amino acids

A simple synthetic method for the preparation of optically active pyrimidinyl α-amino acids is presented. A nucleophilic ipso-substitution reaction between 2-(benzylsulfonyl)-4-isopropoxypyrimidines and a nucleophilic side chain of several protected natural α-amino acids is investigated to obtain new pyrimidin-2-yl α-amino acids. A detailed optimisation study of this reaction is discussed. Moreover, the selective O-alkylation of 2-(benzylsulfanyl)-4(3H)pyrimidinones with a hydroxylic side chain of some natural α-amino acids under Mitsunobu conditions is studied as a method to prepare new pyrimidin-4-yl α-aminoesters.     

A new approach to the synthesis of cyclic ethers via the intermolecular allylation of α-acetoxy ethers and ring-closing metathesis

A concise synthesis of the isolaurepinnacin skeleton 6 was achieved via the intermolecular allylation of the α-acetoxy ether 3 followed by ring-closing metathesis. This methodology was successfully applied to the convergent synthesis of the oxocene 15, an advanced synthetic intermediate for the total synthesis of laurencin.     

A Paterno-Büchi approach to the synthesis of merrilactone A

A six-step approach to the tetracyclic core of merrilactone A is described that uses an intramolecular Paterno-Büchi photoaddition to install the key oxetane ring. Irradiation of bicyclic enone 16, constructed through cyclopentenone alkylation followed by a domino oxy-/carbopalladation reaction, produces the tetracyclic oxetane 17 in excellent yield, having the core carbon skeleton of the target compound merrilactone A. [reaction: see text]     

A new synthesis of α-fluorovinylsulfones utilizing the Peterson olefination methodology

α-Fluoro-α-silyl-substituted sulfones 1 are readily prepared from fluoromethyl phenyl sulfone and the appropriate silyl chloride. The use of TBSCl improves both the stability and yield of 1. Lithium derivatives 4 undergo a smooth Peterson olefination reaction with less-enolizable carbonyl compounds to give moderate to good yields of the expected α-fluorovinylsulfones 6, in some cases with high E-stereoselectivity. One-pot reaction with 4 generated in situ from fluoromethyl phenyl sulfone in tetrahydrofuran (THF) also proceeds smoothly, particularly with aldehydes.     

Novel approach to the synthesis of aliphatic and aromatic α-keto acids

A new practical and efficient synthesis of α-keto acids was accomplished starting from the synthon 1,4-diacetylpiperazine-2,5-dione. The synthesis encompasses both aromatic and aliphatic substrates proving to be versatile and innovative with excellent carbon economy and recycling of the glycine by-product.     

Systematic approach to the chemical synthesis of arabidopyrones,the unique α-pyrones of Arabidopsis metabolites

Abstract

Total synthesis of two arabidopyrones, iso-arabidopyl alcohol (1) and iso-arabidopic acid (2) isolated from Arabidopsis thaliana was achieved for the first time using Claisen condensation and Wittig reaction as the key steps. In addition, arabidopic acid (4) was synthesized from the methyl ester of arabidopyl alcohol (3). Thus, chemical synthesis of the unique natural α-pyrones 1–4 was accomplished with a short synthetic route by a systematic approach from readily available substances.     

A new strategy for the stereoselective synthesis of unnatural α-amino acids

A new method for the synthesis of racemic non-proteinogenic α-amino acids has been developed, which involves (i) hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron rich alkenes such as enol ethers, enamines and allylsilanes, (ii) NaCNBH₃ reduction of the CN bond in the oxazines thus generated, the stereochemistry of the products being controlled by epimerisation of the thermodynamically less stable isomer to the more stable one, (iii) protection of the N-H group as N-Boc and (iv) finally, N-O bond cleavage of both free and protected products to give proline or bis-homoserine derivatives, respectively. An example with concomitant reduction of the carboxylate group, resulting in the formation of the respective amino alcohol is reported. Applying this methodology to a homochiral enol ether, the protected parent d-proline was prepared in enantiomerically pure form, whereas the asymmetric synthesis of the respective bis-homoserine was unsuccessful.     

A convergent approach for the total synthesis of the α-glucosidase inhibitor (−)-panaxjapyne-C

The stereoselective total synthesis of (?)-panaxjapyne-C was accomplished in a convergent fashion. The synthesis utilizes the readily available enantiomers l-(+)-diethyltartrate and d-(?)-diethyltartrate and involves a Cadiot–Chodkiewicz coupling reaction, and an Ohira–Bestmann reaction as the key steps.     

A new approach to the synthesis of N-monosubstituted aniline and its derivatives via β-cyclodextrin host-guest complexes

A novel method for the synthesis of N-monosubstituted aniline and its derivatives via β-cyclodextrin （CD） host-guest complexes has been presented. The mild reaction gives the title compounds with high selectivity in good yields of 90-98%.     

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.     

Synthesis of new optically active α,α′,β‐trisubstituted‐β‐lactones as monomers for stereoregular biopolyesters

Various optically active (4R)‐alkyloxycarbonyl‐3,3‐dialkyl‐2‐oxetanones as monomers were synthesized from L‐(S)‐malic acid in six steps to prepare a new family of stereopolyesters for biomedical applications. The synthesis began with an esterification followed of a dialkylation in the aim to introduce hydrophobic groups as methyl or reactive group as allyl. Then, a saponification has permitted to obtain the corresponding diacids that reacted with appropriate alcohols to furnish different monoesters. The last and most important step was activation of hydroxyl group of monoesters with the asymmetric carbon configuration inversion according to the Mitsunobu reaction. Thus, this reaction has provided lactones from monoesters with 100% enantiomeric excess which was confirmed by ¹H NMR and by the synthesis of corresponding isotactic and semicrystalline homopolyesters. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2586–2597     

Synthesis of Phenanthrene Derivatives through the Reaction of an α,α‐Dicyanoolefin with α,β‐Unsaturated Carbonyl Compounds

Phenanthrene derivatives were prepared by reacting an α,α‐dicyanoolefin with different α,β‐unsaturated carbonyl compounds resulting from Wittig reaction of ninhydrin and phosphanylidene or condensation of barbituric acid and an aldehyde. The easy procedure, mild and metal‐catalyst free, reaction conditions, good yields, and no need for chromatographic purifications are important features of this protocol. The structures of the product of type 3 and 5 were corroborated spectroscopically (IR, ¹H‐ and ¹³C‐NMR, and EI‐MS). A plausible mechanism for this type of reaction is proposed (Scheme 1).     

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.     

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.     

A Convenient Halogenation Procedure for the Preparation of α-Halocarbonyl Compounds

Except for substituted acetophenones (p-Y-C₆H₄COCH₃, Y=H, Br, CH₃O), simple ketones, β-ketoesters and 1,3-diketones reacted smoothly with a preformed homogeneous mixture of hydrochloric acid and potassium permanganate in acetonitrile to give moderate to good yields of the corresponding α-chlorocarbonyl compounds. Mixtures of α-chloro- and α,α-dichlorocarbonyl compounds were obtained for substituted acetophenones. Brominations proceeded similarly with higher yields when the hydrochloric acid was replaced with hydrobromic acid.     

A convenient synthesis of α,α′‐ homo‐ and α,α′‐hetero‐bifunctionalized poly(ε‐caprolactone)s by ring opening polymerization: The potentially valuable precursors for miktoarm star copolymers

Two new ring opening polymerization (ROP) initiators, namely, (3‐allyl‐2‐(allyloxy)phenyl)methanol and (3‐allyl‐2‐(prop‐2‐yn‐1‐yloxy)phenyl)methanol each containing two reactive functionalities viz. allyl, allyloxy and allyl, propargyloxy, respectively, were synthesized from 3‐allylsalicyaldehyde as a starting material. Well defined α‐allyl, α′‐allyloxy and α‐allyl, α′‐propargyloxy bifunctionalized poly(ε‐caprolactone)s with molecular weights in the range 4200–9500 and 3600–10,900 g/mol and molecular weight distributions in the range 1.16–1.18 and 1.15–1.16, respectively, were synthesized by ROP of ε‐caprolactone employing these initiators. The presence of α‐allyl, α′‐allyloxy and α‐allyl, α′‐propargyloxy functionalities on poly(ε‐caprolactone)s was confirmed by FT‐IR, ¹H, ¹³C NMR spectroscopy, and MALDI‐TOF analysis. The kinetic study of ROP of ε‐caprolactone with both the initiators revealed the pseudo first order kinetics with respect to ε‐caprolactone consumption and controlled behavior of polymerization reactions. The usefulness of α‐allyl, α′‐allyloxy functionalities on poly(ε‐caprolactone) was demonstrated by performing the thiol‐ene reaction with poly(ethylene glycol) thiol to obtain (mPEG)₂‐PCL miktoarm star copolymer. α‐Allyl, α′‐propargyloxy functionalities on poly(ε‐caprolactone) were utilized in orthogonal reactions i.e copper catalyzed alkyne‐azide click (CuAAC) with azido functionalized poly(N‐isopropylacrylamide) followed by thiol‐ene reaction with poly(ethylene glycol) thiol to synthesize PCL‐PNIPAAm‐mPEG miktoarm star terpolymer. The preliminary characterization of A₂B and ABC miktoarm star copolymers was carried out by ¹H NMR spectroscopy and gel permeation chromatography (GPC). © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 844–860     

An efficient and convenient transformation of α-haloketones to α-hydroxyketones using cesium formate

A new safe and convenient transformation has been developed. In the presence of cesium formate in dry MeOH solution, α-haloketones underwent direct conversion reaction to afford α-hydroxyketone in excellent yields. Furthermore, this methodology can be extended and applied in 2-chloro-N-(1,3-diphenyl-1H-pyrazol-5-yl)acetamide, 2-chloro-N-(2,6-dimethylphen-yl)acetamide, 1-(bromomethylsulfonyl)benzene, and N-(bromomethyl)phthalimide to give the corresponding products in moderate to excellent yields.     

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.     

Studies on the Mass Spectra of N‐Aryl α,β‐Unsaturated γ‐Lactams

The mass spectra of a series of N‐aryl α,β‐unsaturated γ‐lactams were studied. Besides the molecular ion, the three characteristic fragments such as [M⁺‐29], [M⁺‐55], and [M⁺‐82] were commonly found in a series of N‐Aryl α,β‐unsaturated γ‐lactams in EI/MS. Further more the mechanism for the interpretation of these fragments is also de scribed.