Preparation of functional benzofurans, benzothiophenes, and indoles using ester, thioester, and amide via intramolecular Wittig reactions

Preparation of new types of highly functional benzofurans, benzothiophenes, and indoles is realized via intramolecular Wittig reactions with the corresponding ester, thioester, and amide functionalities. The key intermediates, phosphorus ylides, presumably result from the addition of Bu(3)P toward aldehydes followed by acylation and deprotonation. Synthesis of functional benzofurans directly starting from salicylic aldehyde derivatives with acid chlorides in a one-step procedure is also developed.     

Synthesis and properties of new fluorinated ester,thioester, and amide substituted polythiophenes. Towards superhydrophobic surfaces

A series of new fluorinated polythiophenes has been synthesized by oxidative chemical and electrochemical polymerization and by Ullmann coupling. The substitution with the perfluoroalkyl alkyl chain CH₂CH₂C₆F₁₃ on the 3 position of the thiophene ring is performed via an ester, thioester, or amide connector, (CH₂)_m‐C(O)X, m = 0–2, with a view to investigating the role of the linker on the polymerization and on the properties of the corresponding polymers. The bromination of the monomers at the 2 and 5 positions allows the use of Ullmann coupling to form soluble fluorinated oligomers. The electron affinity was determined from cyclic voltammetry and a value of 3.1 eV was found for the ester derivative; such materials represent interesting candidates for use in light‐emitting devices or as an electron accepting material in photodiodes/solar cells. The oxidative polymerizations need the connector to be spaced out from the heterocycle to reduce its withdrawal effect. The ester, thioester, and amide spacer determined to a large extent the efficiency of the oxidative polymerization, and particularly the electropolymerization, as well as the solubility of the polymers formed. All the polymers were analyzed by GPC and by UV–visible and fluorescence spectroscopies. The electrochemical oxidation of the thioester and amide group prevents the formation of electroactive films by electropolymerization. But in the case of the ester group, the electroformed polymer exhibits exceptional stable superhydrophobic and lipophobic properties because of a porous surface and the presence of a fluorinated chain that confers low surface energy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 4707–4719, 2007     

Easy selective generation of (lithiomethyl)cyclopropane or homoallyllithium by a chlorine-lithium exchange

The reaction of (chloromethyl)cyclopropane 5 with lithium and a catalytic amount of DTBB (5 mol %) in the presence of different carbonyl compounds [Et₂CO, n-Pr₂CO, (c-C₃H₅)₂CO, (CH₂)₅CO, PhCOMe, t-BuCHO, i-PrCHO, PhCHO] as electrophiles in THF at −78 °C leads, after hydrolysis with water, to the corresponding cyclopropyl alcohols 6. However, when the same starting material is lithiated using naphthalene as the arene catalyst in ether at 0 °C and then reacts with the same series of electrophiles, the final hydrolysis with water yields the corresponding unsaturated alcohols 7.     

RNA-catalyzed thioester synthesis

A series of efficient ribozymes with thioester synthetase activities have been isolated from CoA-linked RNA libraries containing four different lengths (30N, 60N, 100N, and 140N) of random nucleotide regions. Competitive evolution of these size-heterogeneous CoA-RNA libraries resulted in an RNA size population in the order of 30N > 60N > 100N > 140N. From isolated clones in the 30N and 60N size groups, two predominant RNA sequences, TES1 (30N) and TES33 (60N), have been shown to catalyze the synthesis of different thioesters using various acyl adenylates as the substrates. Together with our previous findings, the current results demonstrate a CoA thioester synthetic pathway catalyzed by individual metabolic ribozymes, and suggest a likely mechanism for thioester synthesis and utilization in an RNA world.     

Staudinger ligation: a peptide from a thioester and azide

[reaction: see text] The technique of native chemical ligation enables the total chemical synthesis of proteins. This method is limited, however, by an absolute requirement for a cysteine residue at the ligation juncture. Here, this restriction is overcome with a new chemical ligation method in which a phosphinobenzenethiol is used to link a thioester and azide. The product is an amide with no residual atoms.     

Efficient microwave-assisted tandem N- to S-acyl transfer and thioester exchange for the preparation of a glycosylated peptide thioester

A peptide carrying a mercaptomethylated proline derivative at the C-terminus was prepared by solid-phase peptide synthesis (SPPS) and converted to the thioester of 3-mercaptopropionic acid (MPA) by aqueous MPA under microwave irradiation conditions. This post-SPPS thioesterification reaction was successfully applied to the synthesis of a glycopeptide thioester composed of 25 amino acid (AA) residues, which was then used for the preparation of a 61-AA glycopeptide by the thioester condensation method.     

Stereoselective reactions of a thioester butanediacetal with various electrophiles

The reactions of the lithium enolate of S-ethyl (2R,5R,6R)-5,6-dimethoxy-5,6-dimethyl-[1,4]-dioxane-2-carbothioate were investigated in the presence or absence of hexamethylphosphoramide (HMPA). Fluorination gave a single isomer with a much better yield than for the corresponding methyl ester. Alkylation with alkyl halides strongly depended upon their structure. Without HMPA, only methyl iodide reacted with moderate yield and gave a single isomer. In the presence of HMPA, all of the alkyl halides reacted almost quantitatively (81–98% yield) with moderate stereoselectivity and preferentially gave products with the alkyl chain attached at the equatorial position. The silyl enol ether obtained from the thioester had the opposite geometry to that obtained from the methyl ester, which thus explains the difference in stereoselectivity between these two compounds.     

Synthesis,structural and spectroscopic study of aromatic thioester compounds

Eight novel thioesters were obtained and characterized by elemental analysis, mass spectrometry, infrared and NMR spectroscopy. The data were analyzed on the basis of the relevant resonance structures. The X-ray single crystal structure of o-methoxythiophenyl 4-methylbenzoate is reported.     

Peptide thioester formation using standard Fmoc-chemistry

A highly efficient and simple Fmoc-based preparation of peptide ^αthioesters is presented. After Fmoc/t-butyl solid-phase synthesis on 2-chlorotrityl resin the C-terminal carboxylic group of the protected peptide is directly converted to the corresponding thioester. The method leads to very high yields, shows a low level of epimerization and can be easily applied also for the preparation of long peptide ^αthioesters as demonstrated for the 41 amino acid N-terminal fragment of pro-neuropeptide Y (proNPY 1-40).     

Poly(thioester)s

Syntheses and properties of aliphatic and aromatic polythioesters (PTEs) were reviewed including polythiocarbonates and polythiourethanes. The content is subdivided into the following sections: PTEs of aliphatic α‐mercapto carboxylic acid, PTEs of ω‐mercapto carboxylic acids, PTEs derived from α,ω‐dimercapto alkanes, aromatic poly(thioester)s, aliphatic poly(thiocarbonate)s, aliphatic poly(thiourethane)s and aromatic polythiocarbonates. The synthetic strategies reviewed in this article include anionic and cationic ring‐opening polymerizations, polycondensations in bulk, polycondensations in solutions, interfacial polycondensations and in vitro enzymatic polycondensations.     

Remote oxidation of a steroidal amide,ether, and sulfonate

Template directed halogenation of steroids may be performed in the presence of an amide, ether, or sulfonate.     

Protein thioester synthesis enabled by sortase

Proteins containing a C-terminal thioester are important intermediates in semisynthesis. Currently there is one main method for the synthesis of protein thioesters that relies upon the use of engineered inteins. Here we report a simple strategy, utilizing sortase A, for routine preparation of recombinant proteins containing a C-terminal (α)thioester. We used our method to prepare two different anthrax toxin cargo proteins: one containing an (α)thioester and another containing a D-polypeptide segment situated between two protein domains. We show that both variants can translocate through protective antigen pore. This new method to synthesize a protein thioester allows for interfacing of sortase-mediated ligation and native chemical ligation.     

Piptigrine, a new insecticidal amide from Piper nigrum Linn

A new insecticidal amide piptigrine (1) possessing highly extended conjugation was isolated from the dried ground seeds of Piper nigrum Linn. along with the known amides piperine and wisanine (hitherto unreported from this plant). The structure of 1 has been elucidated as 1-[9-(3',4'-methylenedioxyphenyl)-4E,6E,8E-nonatrienoyl]piperidine through extensive 1D- and 2D-NMR (COSY-45, NOESY, J-resolved, HMQC, HMBC and NOESY studies. The known compounds have been identified through comparison of their spectral data with those reported in literature. 1 exhibited toxicity of 15.0 ppm against fourth instar larvae of Aedes aegypti Liston.     

Poly(sulfone ether amide amide)s as a new generation of soluble, thermally stable polymers

A new sulfone ether amide diamine was synthesized via three steps, starting from reaction of 4-aminophenol with 4-nitrobenzoyl chloride in the presence of propylene oxide afforded N-(4-hydroxy phenyl)-4-nitrobenzamide (HPNB). In the next step, reduction of nitro group resulted in preparation of 4-amino-N-(4-hydroxy phenyl) benzamide (AHPB). Final step in the preparation of diamine was the reaction of AHPB with bis(4-chlorophenyl) sulfone in the presence of K₂CO₃. All the materials were characterized using conventional spectroscopic methods. Poly(sulfone ether amide amide)s were synthesized by polycondensation reactions of prepared diamine with different diacid chlorides (aromatic and aliphatic ones). The obtained polymers were fully characterized and their physical properties including thermal behavior, thermal stability, solubility, and inherent viscosity were studied.     

Synthesis of a thioester linker precursor for a general preparation of peptide C-terminal thioacids

A general procedure to prepare peptide thioacids by solid-phase peptide synthesis is presented. The method involves the synthesis of 4-[α-(S-acetyl)mercaptobenzyl]phenoxyacetic acid as general precursor. This reagent once attached to a solid support is derivatized with the Boc-amino acid of choice after deprotection of the thiol.     

Tailbiter: a new amide foldamer

Hydrogen bond directed folding of a synthetic polyamide was studied in chloroform solution, and the three-dimensional structure of the foldamer determined using 1H NMR chemical shifts.     

Synthesis of the N-acetylcysteamine thioester of seco-proansamitocin

[structure: see text] The enantioselective total synthesis of the N-acetylcysteamine thioester of seco-proansamitocin, a key biosynthetic intermediate of the highly potent antitumor agent ansamitocin, is described, which twice utilizes the Nagao acetate aldol reaction, as well as an indium-mediated alkynylation of a benzyl bromide followed by carboalumination. The key step is a Heck reaction between two terminal alkenes for merging the two major fragments.