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Prior to detailed process design, it is vital to first generate a good flowsheet that meets particular objective. This is particularly the case in bio-based materials and products, where, given a range of chemistries, the synthesis problem is not about the best way to make a particular product but rather the best way to convert a specific feedstock. In order to do so, an optimisation-based framework, which can be used to identify the optimal configuration of a process network that consists of both reactions and separation systems to achieve maximum economic potential, is presented in this paper. A process superstructure, which includes the concept of master reaction stages and subsidiary separation stages, is introduced to facilitate the theory. The problem is formulated as a generalised mixed integer linear programming (MILP) model which accounts for the simultaneous selection of products and identification of the process configuration. The solution of the optimisation problem includes the best possible economic performance, identification of active reactions, reaction ordering and separation sequences along with the corresponding flowsheet of the optimal process. The economic criterion takes account of raw materials costs, product values and separation related costs. Two bio-based chemical case studies are presented to illustrate the applicability of the proposed methodology.

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CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE DERIVATIVES AND METHODS OF USE THEREOF FOR THE TREATMENT OF VIRAL DISEASES

The present invention relates to Cyclic Phosphate Substituted Nucleoside Derivatives of Formula (I), and pharmaceutically acceptable salts thereof, wherein A, B, Q, V, R1, R2 and R3 are as defined herein. The present invention also relates to compositions comprising a Cyclic Phosphate Substituted Nucleoside Derivative, and methods of using the Cyclic Phosphate Substituted Nucleoside Derivatives for treating or preventing HCV infection in a patient.

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<3+4> and <3+5> Annulation Reactions of alpha-(Phenylthio) Dicarbonyl Electrophiles with Bis(trimethylsilyl) Enol Ethers: Synthesis of Highly Functionalized Medium Ring Cycles

The <3+4> and <3+5> annulations of bis(trimethylsilyl) enol ethers with 1,4- and 1,5-dicarbonyl electrophiles bearing alpha-phenylthio substituents leads to the formation of bicyclic <3.2.1> and <3.3.1> ethers with good regiochemical and stereochemical control.Subsequent oxidation of the phenylthio moiety followed by reduction with SmI2 constitutes a high-yielding and regioselective process for cleavage of the bridging ether linkage.The overal strategy provides a synthetic pathway for the synthesis of highly functionalized medium ring carbocycles.

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Enantioselective hydrolyses with Yarrowia lipolytica: A versatile strain for esters, enol esters, epoxides, and lactones

Racemic secondary esters 1-3, gamma-lactones 8-9, and styrene oxide 7 are kinetically resolved via hydrolysis with Yarrowia lipolytica YL2 strain. The enantioselective hydrolysis of prochiral enol esters 4-6 to the corresponding homochiral carbonyl compounds 13-15 is also described. Subsequent reduction of the ketone 13 and of the aldehyde 15 can be avoided using lyophilised cells.

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Palladium-catalyzed intramolecular arylation of an anilide enolate, application to an efficient formal total synthesis of physovenine

An expedient formal total synthesis of the calabar alkaloid physovenine was reported. The key step involves an oxindole synthesis via palladium-catalyzed intramolecular arylation of o-bromoanilide.

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Tetrahydrofuran – Wikipedia,
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Use of Bromine and Bromo-Organic Compounds in Organic Synthesis

Bromination is one of the most important transformations in organic synthesis and can be carried out using bromine and many other bromo compounds. Use of molecular bromine in organic synthesis is well-known. However, due to the hazardous nature of bromine, enormous growth has been witnessed in the past several decades for the development of solid bromine carriers. This review outlines the use of bromine and different bromo-organic compounds in organic synthesis. The applications of bromine, a total of 107 bromo-organic compounds, 11 other brominating agents, and a few natural bromine sources were incorporated. The scope of these reagents for various organic transformations such as bromination, cohalogenation, oxidation, cyclization, ring-opening reactions, substitution, rearrangement, hydrolysis, catalysis, etc. has been described briefly to highlight important aspects of the bromo-organic compounds in organic synthesis.

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Ester hydrogenation catalyzed by a ruthenium(II) complex bearing an N-heterocyclic carbene tethered with an “nH2” group and a DFT study of the proposed bifunctional mechanism

A ruthenium(II) catalyst containing an NHC-amine (NHC = Nheterocyclic carbene) ligand (C-NH2) catalyzes the H2-hydrogenation of various esters and lactones at 50 C and 25 bar of H2 pressure, mild reaction conditions compared with other reported catalysts. A maximum turnover frequency of 1510 h-1 for the hydrogenation of phthalide with a conversion of 96% is achieved in 4 h. DFT calculations suggest a concerted, asynchronous bifunctional mechanism for homogeneous ester hydrogenation; a proton transfer step from the N-H group of a ruthenium hydride-amine complex to the carbonyl group has the largest energy barrier in the catalytic cycle. A surprising observation is that methyl pivalate ( tBuCOOCH3) is hydrogenated much more rapidly than is tert-butyl acetate (CH3COOtBu). This is explained by the energetics of the rate-determining step of the proposed Ru-H/N-H bifunctional mechanism.

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Intramolecular nucleophilic acyl substitution reactions mediated by XTi(O-i-Pr)3 (X = Cl, O-i-Pr)/2i-PrMgBr reagent. Efficient synthesis of functionalized organotitanium compounds from unsaturated compounds

Treatment of acetylenic or olefinic carbonates and esters with a low-valent titanium reagent diisopropoxy(eta2-propene)titanium (1), readily generated by the reaction of Ti(O-i-Pr)4 or ClTi(O-i-Pr)3 with 2i-PtMgX, resulted in an intramolecular nucleophilic acyl substitution (INAS) reaction to afford organotitanium compounds having a carbonyl functional group, in good to excellent yields. Thus, the treatment of alkyl alkynyl carbonates 2 or alkyl alkenyl carbonates 4 with 1 gave organotitanium compounds having a lactone and/or ester group. Similarly, alkyl alkynoates 10 or alkynyl esters 14 of carboxylic acids reacted with 1 to give organotitanium compounds having a cyclic or acyclic ketone group, respectively. Thus, the reaction provides, after hydrolysis, five- or six-membered alpha-alkylidene lactones and/or alpha,beta-unsaturated esters from 2, gamma-butyrolactone derivatives from 4, five- or six-membered alpha-alkylidene cyclic ketones from 10, and acyclic alpha,beta-unsaturated ketones 15 from 14. In all cases, the yields are excellent and the generation of the organotitanium compounds was confirmed by deuterolysis. The organotitaniums 6 and 11c reacted smoothly with iodine to afford 2-(iodomethyl)-4-butanolide (9) and alpha-[iodo(trimethylsilyl)methylidene]cyclopentanone, respectively. The organotitanium compounds obtained here also reacted with aldehydes to give the corresponding adducts, thus opening up a new access to substituted alpha,beta-butenolides from 2, to gamma-butyrolactones from 4, and to the corresponding tetrasubstituted furan from 10 and 14.

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EFFETS DES SUBSTITUANTS SUR LA CONFORMATION DU CYCLE Gamma-LACTONIQUE

The structural study of some gamma-butyrolactones substituted (i) in position 2 (position alpha): C4H4O2Br2 (II) and C4H5O2R or (ii) in position 3 or 4 (beta or beta’): C4H5O2Cl (VIII) and IX) has been carried out by using different techniques of physical chemistry.Crystallographic data analysis demonstrates that in the solid state 2,2-dibromo-gamma-butyrolactone, unlike the 2,2-diphenyl-gamma-butyrolactone, adopts an “envelope” structure which is comparable to those of compounds (III) and (IV).Spectroscopic data relative to the methylene bending mode delta(CH2) are interpreted for the dissolved state in terms of rigid (III, IV, V, IX) or exchanging (VI, VII, VIII) “envelope” forms.For alpha and beta halogenated derivatives (VI, VII, VIII), quantitative analysis of infrared spectra shows a pseudo-axial predominance in apolar solvents, as found by application of the PCILO method.Interpretation of NMR spectra recorded at 250 MHz (III, IV, V, VI) confirms the data obtained by vibrational spectroscopy.

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PYRROLO[1,2-B]PYRIDAZINE COMPOUNDS AND THEIR USES

Disclosed are novel CRF receptor antagonists and their use as treatment of a variety of disorders, including disorders manifesting hypersecretion of CRF or associated with CRF or CRF receptors, such as anxiety, and depression. CRF receptor antagonists of the invention have the structure of formula (1): including stereoisomers or mixture of stereoisomers, pharmaceutically acceptable prodrugs, or pharmaceutically acceptable salts thereof, wherein in formula (I) R is H or Me.

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Tetrahydrofuran – Wikipedia,
Tetrahydrofuran | (CH2)3CH2O – PubChem