- Synthetic Studies toward the C14-C29 Fragment of Mirabalin
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A convergent synthesis of one isomer of the C14-C29 fragment of mirabalin is disclosed. The key steps include a Marshall allenylation, a Mukaiyama aldol reaction and a Crimmins aldolization, which allow the control of 10 out of 25 stereogenic centers pres
- Cornil, Johan,Echeverria, Pierre-Georges,Reymond, Sébastien,Phansavath, Phannarath,Ratovelomanana-Vidal, Virginie,Guérinot, Amandine,Cossy, Janine
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- Novel synthesis of the ocular age pigment A2-E: new method for substituted pyridine synthesis via azaelectrocyclization.
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[reaction: see text] The formal synthesis of the ocular age pigment A2-E was achieved by the efficient one-pot preparation of the substituted pyridine, which involves the aza-6pi-electrocyclization of the Schiff base derived from (E)-3-carbonyl-2,4,6-trienal followed by oxidation.
- Tanaka,Katsumura
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Read Online
- First highly efficient asymmetric synthesis of the Hyrtios erectus diketotriterpenoid
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The first highly efficient asymmetric synthesis of the diketotriterpenoid 1, isolated from the Indonesian marine sponge Hyrtios erectus, in good overall yield and employing simple starting materials such as butanone, is described. Both stereogenic centres at the C-6 and C-19 positions of the C2-symmetrical molecule were generated via α-alkylation employing the SAMP/RAMP hydrazone method with high asymmetric inductions (de, ee ≥ 96%). The absolute configuration of the natural material was determined as R,R.
- Enders, Dieter,Schuesseler, Thomas
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- Synthesis and in vitro activity evaluation of 2',3'-c-dimethyl carbocyclic nucleoside analogues as potential anti-HCV agents
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The first synthetic route of novel 2'(β),3'(β)-C-dimethyl carbodine analogues is described. The key intermediate cyclopentenyl alcohol 11(β) prepared from Weinreb amide 4 via ring-closing metathesis (RCM) and vicinal dihydroxylation. Coupling of 12 with n
- Ko, Ok Hyun,Hong, Joon Hee
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Read Online
- Rapid and scalable synthesis of chiral bromolactones as precursors to α-exo-methylene-γ-butyrolactone-containing sesquiterpene lactones
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The sesquiterpene lactones cover a diverse and pharmacologically important diversity space. In particular, the electrophilic α-exo-methylene-γ-butyrolactone moiety that is preponderant in this natural product family has been shown to readily engage in cov
- Lagoutte, Roman,Pastor, Miryam,Berthet, Mathéo,Winssinger, Nicolas
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- Synthetic study toward total synthesis of (±)-germine: Synthesis of (±)-4-methylenegermine
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The total synthesis of 4-methylenegermine is described.
- Stork, Gilbert,Yamashita, Ayako,Hanson, Robert M.,Phan, Ly,Phillips, Eifion,Dubé, Daniel,Bos, Pieter H.,Clark, Andrew J.,Gough, Maxwell,Greenlee, Mark L.,Jiang, Yimin,Jones, Keith,Kitamura, Masato,Leonard, John,Liu, Tongzhu,Parsons, Philip J.,Venkatesan, Aranapakam M.
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- Formal synthesis of belactosin A and hormaomycin via a diastereoselective intramolecular cyclopropanation of an α-nitro diazoester
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Chemical Equation presented An efficient and convenient methodology for the synthesis of the 3-(trans-2-aminocyclopropyl) alanine and 3-(trans-2- nitrocyclopropyl) alanine moieties found In the core of belactosln A and hormaomycin, respectively, Is reported. By using an enantioenriched substituted α-nitro diazoester In a diastereoselective Intramolecular cyclopropanatlon reaction, the trans-nitrocyclopropyl alanine moiety can be obtained efficiently In five steps from the Initial α-nitrocyclopropyl lactone unit, thus achieving the synthesis of the cyclopropane core of the two natural products.
- Vanler, Sebastien F.,Larouche, Guillaume,Wurz, Ryan P.,Charette, Andre B.
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- Total synthesis of the mycolactones.
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[structure: see text] The first total synthesis of the mycolactones is reported. This work unambiguously confirms our earlier relative and absolute stereochemical assignment of the mycolactones.
- Song, Fengbin,Fidanze, Steve,Benowitz, Andrew B,Kishi, Yoshito
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Read Online
- Technical production of aldehydes by continuous bleach oxidation of alcohols catalyzed by 4-hydroxy-TEMPO
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Aldehydes can be easily prepared from the corresponding alcohols in good to excellent yields by oxidation with technical bleach and catalytic amounts of 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl (1b, 4-hydroxy TEMPO, "HOT"). Whereas the well-known batch process performed on lab scale is not suitable for the technical synthesis especially of activated β-substituted aldehydes, this transformation can be performed continuously in a simple tube reactor. This layout meets all requirements necessary for the process, i.e., turbulent mixing of the biphasic mixture, removal of heat, short contact times, and high output. Thus, a single tube of 3 mm diameter renders about 60 mol of aldehyde per day.
- Fritz-Langhals, Elke
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Read Online
- A mild and efficient approach to enantioenriched α-hydroxyethyl α,β-unsaturated δ-lactams
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A straightforward approach toward enantioenriched α-substituted α,β-unsaturated δ-lactams is described. Although a considerable number of approaches toward α,β-unsaturated δ-lactams have been reported, there are relatively few examples of enantioenriched α,δ-disubstituted α,β-unsaturated δ-lactams formation. The δ-stereocenter was formed by addition of allylmagnesium bromide to an N-tert-butylsulfinyl imine. The α,β-unsaturated δ-lactam was furnished by ring-closing metathesis. Although Baylis-Hillman chemistry failed on this cyclic compound, introduction of the hydroxyethyl group prior to ring-closing metathesis was successful. A Baylis-Hillman reaction was used to introduce the substituent at the α-position of the α,β-unsaturated lactam.
- Han, Seo-Jung,Stoltz, Brian M.
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- Application of[5+2] cycloaddition toward the functionalized bicyclo[4.3.1]decane ring system: Synthetic study of phomoidride B (CP-263,114)
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Oxidopyrylium-alkene [5+2] cycloaddition was utilized in combination with an intramolecular aldol reaction to construct the bicyclo[4.3.1]decane ring system of phomoidride B (CP-263,114).
- Ohmori, Naoki
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Read Online
- Synthesis of Optically Active A-Factor
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(3R)-(-)-A-factor and (3S)-(+)-A-factor are synthesised via the same chiral intermediate 6, the synthesis of which proceeds through a Johnson-Claisen rearrangement key step.
- Parsons, Philip J.,Lacrouts, Pierre,Buss, A. D.
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- Ozonolysis of Alkynes - A Flexible Route to Alpha-Diketones: Synthesis of AI-2
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A mild procedure for the low-temperature conversion of alkynes to diketones has been developed and employed in the synthesis of AI-2.
- Alterman, Joshua L.,Halverson, Larry J.,Kraus, George A.,Stroud, Marissa Roghair,Vang, Dua X.
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- Synthetic study of phomoidride B (CP-263,114); utilization of the oxidopyrylium [5 + 2] cycloaddition
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The highly functionalized core structure of phomoidride B (CP-263,114) was pursued by using intermolecular oxidopyrylium-alkene cyclization as one of the key steps.
- Ohmori
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Read Online
- Hydroxynitrile lyase catalyzed enantioselective HCN addition to O-protected α-hydroxyaldehydes
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Various O-protected glycol- and racemic lactaldehydes 3 and 6 as well as O-allyl protected racemic α-hydroxyaldehydes 7 (R1=Et, Pr, Bu) have been prepared to investigate and perform a stereoselective Kiliani-Fischer synthesis by hydroxynitrile lyase (HNL) catalyzed addition of HCN. From all protecting groups investigated the allyl moiety was most suitable. (R)-PaHNL from bitter almonds (Prunus amygdalus), yielding the (2S)-cyanohydrins 8-10, was found to be a more stereoselective catalyst than (S)-MeHNL from maniok (Manihot esculenta). While (R)-PaHNL led to enantiomeric excesses ≥93%, with (S)-MeHNL the (2R)-cyanohydrins 8-10 were obtained with enantiomeric excesses ≤78%.
- Roos, Juergen,Effenberger, Franz
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Read Online
- Total synthesis of isoquinocyclinone
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The total synthesis of the heptacyclic natural product isoquinocyclinone has been achieved. A Hauser annulation was used to assemble the anthraquinone core structure. The unique 2,4,5,6-tetrahydropyrrolo[2,3-b]pyrrole substructure was prepared by alkyne addition to a lactone intermediate and subsequent Ni 0-mediated cyanide addition, the conversion of an O,O- into an N,O-acetal, and final intramolecular N-alkylation. Hauser annulation: An efficient total synthesis of isoquinocyclinone was achieved using a pentacyclic lactone as the key intermediate (see scheme). The pyrrolo-pyrrole substructure was elaborated by acetylide acylation, conversion of an O,O-acetal into an N,O-acetal, and intramolecular amidine alkylation.
- Dischmann, Mike,Frassetto, Timo,Breuning, M. André,Koert, Ulrich
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Read Online
- Pyrimidine-4 (3H)-ketone heterocyclic compound, preparation method thereof and application of pyrimidine-4 (3H)-ketone heterocyclic compound in medicine
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The invention relates to pyrimidine-4 (3H)-ketone heterocyclic compounds suitable for inhibiting or regulating SHP2, a preparation method of the pyrimidine-4 (3H)-ketone heterocyclic compounds and application of the pyrimidine-4 (3H)-ketone heterocyclic compounds in medicine. Specifically, the invention relates to a compound as shown in a general formula (I) and a pharmaceutically acceptable salt thereof, a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt thereof, a method for treating and/or preventing related diseases mediated by SHP2, especially cancers by using the compound or the pharmaceutically acceptable salt thereof, and a preparation method of the compound or the pharmaceutically acceptable salt thereof. The invention also relates to application of the compound or the pharmaceutically acceptable salt thereof or a pharmaceutical composition containing the compound or the pharmaceutically acceptable salt thereof in preparation of drugs for treating and/or preventing SHP2-mediated related diseases. Wherein each substituent in the general formula (I) is as defined in the specification.
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Paragraph 0349-0351; 0356-0359
(2021/07/21)
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- Total Synthesis and Structure Revision of Halioxepine
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The first total synthesis of halioxepine is accomplished using a 1,4-addition for constructing the quaternary center at C10 and a halo etherification for the generation of the tertiary ether at C7. The correct structure of halioxepine was determined by assembling different enantiomeric building blocks and by changing the relative configuration between C10 and C15.
- Poock, Caroline,Kalesse, Markus
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supporting information
p. 1615 - 1619
(2020/12/23)
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- COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF PARASITIC DISEASES
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The present invention provides a compound of formula (Ia) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, solid forms, combinations of pharmacologically active agents, pharmaceutical compositions and methods of using such compounds and solid forms thereof to treat or prevent parasitic diseases, for example malaria.
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Paragraph 0382; 0385
(2021/04/23)
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- A Unified Strategy for the Asymmetric Synthesis of Highly Substituted 1,2-Amino Alcohols Leading to Highly Substituted Bisoxazoline Ligands
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A general procedure for the asymmetric synthesis of highly substituted 1,2-amino alcohols in high yield and diastereoselectivity is described that uses organometallic additions of a wide range of nucleophiles to tert-butylsulfinimines as the key step. The addition of organolithium reagents to these imines follows a modified Davis model. The diastereoselectivity for this reaction depends significantly on both the nucleophile and electrophile. These highly substituted 1,2-amino alcohols are used to synthesize stereochemically diverse and structurally novel, polysubstituted 2,2′-methylene(bisoxazoline) ligands in high yields.
- Shrestha, Bijay,Rose, Brennan T.,Olen, Casey L.,Roth, Aaron,Kwong, Adon C.,Wang, Yang,Denmark, Scott E.
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p. 3490 - 3534
(2021/02/16)
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- ERK INHIBITORS AND USES THEREOF
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The present disclosure provides compounds and compositions that are inhibitors of ERK1, ERK2, or both, and methods of use thereof.
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Page/Page column 128-129
(2020/06/05)
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- BICYCLIC COMPOUND ACTING AS ROR INHIBITOR
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A bicyclic compound acting as a RORγ inhibitor. Provided are a compound of formula (I) or a pharmaceutically acceptable salt thereof, the compound having a structure as represented by formula (I-A) or formula (I-B). The provided compound of formula (I-A)
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Paragraph 0201; 0204-0205
(2020/07/02)
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- Preparation method of Plazomicin
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The invention discloses a preparation method of Plazomicin. The method uses sisomicin as a starting material, HONB-PNZ is used for protecting aminos at allyl positions, a reaction with hexamethyldisilazane is conducted to prepare a fully-protected silanid
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Paragraph 0041; 0051-0052; 0054
(2020/12/31)
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- Regioselective lithiation of benzyl imidazole: Synthesis and evaluation of new organocatalysts for trans-diol functionalization.
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Benzyl imidazole was successfully lithiated using n-BuLi at ?78 °C and verified by deuterium incorporation. The chemical reaction of the lithiated benzimidazole was explored with a series of different electrophiles. This approach was utilized to synthesiz
- El-Mansy, Mohamed,Ghosh, Ankan,Cheong, Paul Ha-Yeon,Carter, Rich
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supporting information
p. 3131 - 3139
(2019/09/03)
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- Preparation method of pradimicin antibiotics
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The invention provides a preparation method of pradimicin antibiotics, belonging to the field of pharmaceutical chemistry and pharmaceutical engineering. The preparation method comprises the followingsteps: freeing of sisomicin, protection of amino, selective introduction of protective groups, deprotection of amino, and the like. The preparation method is suitable for industrial production, thushaving good market prospects.
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Paragraph 0076; 0077
(2019/01/08)
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- Synthesis method of afatinib degradation impurity
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The invention discloses a synthesis method of afatinib degradation impurity, including steps of: (1) under effect of an oxidant, performing a reaction to a compound (V) to generate a compound (IV); (2) under effect of alkali, performing a reaction to a compound (III) with the compound (IV) to generate a compound (II); (3) under effect of a deprotective agent, performing a reaction to the compound(III) to generate a compound (I). The method is reasonable in difficulty, employs accessible reagents and is simple in operation. The reaction route is represented as follows, wherein R1 is selected from tert-butyldimethylsilyl or tert-butyldiphenylsilyl and R2 is selected from methyl group or ethyl group.
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Paragraph 0019; 0020; 0027; 0028
(2019/01/08)
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- MODULATORS OF ROR-GAMMA
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Provided are novel compounds of Formula I: pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORy. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
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Paragraph 00132
(2017/02/28)
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- MODULATORS OF ROR-GAMMA
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Provided are novel compounds of Formula I: pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORy. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
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Paragraph 00125; 00128
(2017/06/12)
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- BENZIMIDAZOLE DERIVATIVES AS MODULATORS OF ROR-GAMMA
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Provided are novel compounds of Formula I: pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORy. Also provided are pharmaceutical compositions comprising the novel compounds of Formula I and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
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Paragraph 00203-00204
(2017/08/21)
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- N-substituted imidazole carboxylate compound, preparation method and medical uses thereof
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The present invention relates to a compound represented by a general formula (I) or a stereoisomer, a solvate, a pharmaceutically acceptable salt or a eutectic, a composition, a preparation method and medical uses thereof, wherein the general formula (I) is defined in the specification, and each substituent is defined in the specification.
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Paragraph 0341; 0347-0351
(2017/12/13)
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- Modular Synthesis of Diverse Natural Product-Like Macrocycles: Discovery of Hits with Antimycobacterial Activity
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A modular synthetic approach was developed in which variation of the triplets of building blocks used enabled systematic variation of the macrocyclic scaffolds prepared. The approach was demonstrated in the synthesis of 17 diverse natural product-like macrocyclic scaffolds of varied (12–20-membered) ring size. The biological relevance of the chemical space explored was demonstrated through the discovery of a series of macrocycles with significant antimycobacterial activity.
- Dow, Mark,Marchetti, Francesco,Abrahams, Katherine A.,Vaz, Luis,Besra, Gurdyal S.,Warriner, Stuart,Nelson, Adam
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p. 7207 - 7211
(2017/05/31)
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- 3-PHOSPHOGLYCERATE DEHYDROGENASE INHIBITORS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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- 2-(1-HETEROARYLPIPERAZIN-4-YL)METHYL-1,4-BENZODIOXANE DERIVATIVES AS ALPHA2C ANTAGONISTS
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Compounds of formula I (formula I), wherein A is an optionally substituted five-membered unsaturated heterocyclic ring containing 1, 2 or 3 N, O or S ring heteroatom(s) exhibit alpha2C antagonistic activity and are thus useful for the treatment of diseases or conditions of the peripheric or central nervous system.
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Page/Page column 26
(2016/12/22)
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- DIHYDROPYRROLOPYRIDINE INHIBITORS OF ROR-GAMMA
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Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I) and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
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Paragraph 0115; 0118
(2016/06/01)
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- Dihydropyrrolopyridine inhibitors of ROR-gamma
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Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions co
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Page/Page column 47; 48
(2016/11/21)
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- Preparation methods of tert-butyl dimethyl siloxy ethanol and tert-butyl dimethyl siloxy acetaldehyde
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The present invention discloses preparation methods of tert-butyl dimethyl siloxy ethanol and tert-butyl dimethyl siloxy acetaldehyde. The tert-butyl dimethyl siloxy ethanol preparation comprises: adding tert-butyl dimethyl chlorosilane to an organic solvent, dissolving, adding ethylene glycol in a dropwise manner, adding an organic acid binding agent, carrying out a reflux reaction at a temperature of 45-55 DEG C, collecting the product, filtering, collecting the filtrate, carrying out normal pressure rectification at a temperature of 90-110 DEG C to evaporate the solvent, carrying out pressure reducing rectification, and collecting the distillate with a temperature 130 DEG C so as to obtain the tert-butyl dimethyl siloxy ethanol product. The tert-butyl dimethyl siloxy acetaldehyde preparation comprises that the tert-butyl dimethyl siloxy acetaldehyde is prepared from the tert-butyl dimethyl siloxy ethanol under the effect of an oxidizing agent. According to the present invention, the industrial production is achieved, the yield is high, and the purity can be more than or equal to 99%.
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Paragraph 0036; 0037
(2016/10/08)
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- ISOINDOLINE INHIBITORS OF ROR-GAMMA
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Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORγ. Also provided are pharmaceutical compositions comprising the novel compounds of Formula (I) and methods for their use in treating one or more inflammatory, metabolic, autoimmune and other diseases or disorders.
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Paragraph 0182
(2016/06/01)
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- DIHYDROPYRROLOPYRIDINE INHIBITORS OF ROR-GAMMA
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Provided are novel compounds of Formula (I): pharmaceutically acceptable salts thereof, and pharmaceutical compositions thereof, which are useful in the treatment of diseases and disorders mediated by RORy. Also provided are pharmaceutical compositions co
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Paragraph 00146
(2016/05/24)
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- NOVEL CHONDRAMIDE DERIVATIVES
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The present invention provides novel chondramide derivatives of formula (I) which can be used for the treatment of cancer.
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Paragraph 0084
(2015/11/17)
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- Tertiary Amine Promoted Asymmetric Aldol Reaction of Aldehydes
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The direct asymmetric self-aldol reactions of various α-oxyaldehydes catalyzed by tertiary amines have been demonstrated. By using 10 mol-% of quinine catalyst, dimerization products have been prepared in high yields, with good anti-diastereocontrol, and up to 80% ee. The presented enolate-mediated synthesis of protected tetrose sugars has never been accomplished before by chiral tertiary amine organocatalysts.
- Gut, Bartosz,Mlynarski, Jacek
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supporting information
p. 5075 - 5078
(2015/08/18)
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- Stereoselective Synthesis of Lignans of Three Structural Types from a Common Intermediate, Enantioselective Synthesis of (+)-Yangambin
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Enantioselective total synthesis of (+)-yangambin was achieved. The key transformation is one-pot conjugate addition/aldol reaction that involves an enantioenriched benzyl tert-butyl sulfoxide, an enone, and gaseous formaldehyde to construct the bis(pheny
- Syed, Majid Khalil,Murray, Cian,Casey, Mike
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p. 5549 - 5556
(2014/10/15)
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- ANTIBACTERIAL AGENTS
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Antibacterial compounds of formula (I) are provided, as well as stereoisomers and pharmaceutically acceptable salts thereof; pharmaceutical compositions comprising such compounds; methods of treating bacterial infections by the administration of such compounds; and processes for the preparation of such compounds.
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- A convenient access to γ-lactones from O-allyl-α-bromoesters using a one-pot ionic-radical-ionic sequence
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Cognac in the jar! An efficient one-pot sequence for the preparation of γ-lactones is described. Following reduction of α-bromo ester precursors with DIBAL-H and radical cyclization of the resulting O-aluminum acetals, a preparative in-situ Oppenauer-type oxidation of the cyclic O-aluminum acetal using simple aldehydes or ketones gives access to γ-lactones in high yields. Copyright
- Beneteau, Romain,Lebreton, Jacques,Denes, Fabrice
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supporting information; experimental part
p. 1516 - 1520
(2012/09/08)
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- An enantioselective total synthesis of helioporins C and e
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A short and enantioselective total synthesis of helioporins C and E, which are bioactive marine diterpenes containing a serrulatane or amphilectane skeleton, was elaborated. The chirogenic step, i.e. a Cu(I)-catalyzed allylic alkylation of a cinnamyl chlo
- L?lsberg, Wibke,Werle, Susen,Neud?rfl, J?rg-Martin,Schmalz, Hans-Günther
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supporting information
p. 5996 - 5999
(2013/02/23)
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- A ring-closing metathesis (RCM)-based approach to mycolactonesa A/B
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The total synthesis of the mycobacterial toxins mycolactones A/B (1 a/b) has been accomplished based on a strategy built around the construction of the mycolactone core through ring-closing metathesis. By employing the Grubbs second-generation catalyst, t
- Gersbach, Philipp,Jantsch, Andrea,Feyen, Fabian,Scherr, Nicole,Dangy, Jean-Pierre,Pluschke, Gerd,Altmann, Karl-Heinz
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supporting information; experimental part
p. 13017 - 13031
(2012/01/02)
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- One-pot synthesis of fused-tetracyclic scaffolds employing a Lewis acid promoted domino reaction of naphthoquinones
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The facile synthesis of tetracyclic molecular frameworks employing a Lewis acid promoted domino reaction of naphthoquinones with hydroxy- and amino-functionalized cross-conjugated trienes is reported. The reaction cascade involves a heterocyclization via hemiacetal or imine formation, and an intramolecular Diels-Alder cycloaddition. Georg Thieme Verlag Stuttgart - New York.
- Bendiabdellah, Yassine,Villanueva-Margalef, Isabel,Misale, Antonio,Nahar, Kazi S.,Haque, Mohammad R.,Thurston, David E.,Zinzalla, Giovanna
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experimental part
p. 2321 - 2333
(2011/09/19)
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- FUSED HETEROCYCLIC COMPOUND
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The present invention relates to a fused heterocyclic compound having the Formula 1, which is useful as a platelet aggregation inhibitor, a method for preparing the same, and a pharmaceutical composition for inhibiting platelet aggregation comprising the same.
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Page/Page column 62
(2011/07/29)
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- Total synthesis and structural confirmation of brevisamide, a new marine cyclic ether alkaloid from the dinoflagellate Karenia brevis
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The first total synthesis of brevisamide (1) has been accomplished in 21 linear steps starting from cis-but-2-ene-1,4-diol. A synthetic highlight is the Suzuki-Miyaura coupling between an ether ring fragment and a dienol side chain. This result confirmed the structure of 1 isolated from the dinoflagellate Karenia brevis.
- Kuranaga, Takefumi,Shirai, Tomohiro,Baden, Daniel G.,Wright, Jeffrey L. C.,Satake, Masayuki,Tachibana, Kazuo
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scheme or table
p. 217 - 220
(2009/06/20)
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- Syntheses of D-labelled oxidative metabolites of acrylamide and acrylonitrile for the quantification of their toxicities in humans
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Syntheses of the labelled oxidative metabolites of acrylamide and acrylonitrile - reference compounds for the evaluation of human exposure to important toxicants - are reported. For that, L-cystine tert-butyl ester was acetylated and the product reductively cleaved to L-cysteine tert-butyl ester, which reacted with carbamoyl[D3]oxirane (obtained from [D 3]acrylonitrile and 30% aq. H2O2 at pH = 7.0-7.5) and afforded a separable mixture of tert-butyl N-acetyl-S-(2-hydroxy-2- carbamoyl[ D3]ethyl)cysteinate and tert-butyl N-acetyl-S-(1- carbamoyl-2-hydroxy[D3]ethyl)cysteinate (ca. 9:1). Removal of the tert-butyl group in these intermediates with aq. HCl gave the final deuterated internal standards with carbamoyl residues. Protection of the secondary hydroxy group in the major intermediate with tBuMe2SiCl/imidazole in DMF followed by dehydration of the carbamoyl group (trifluoroacetic anhydride/pyridine in CH2Cl2) and stepwise removal of the tert-butyl and tBuMe2Si protecting groups (TFA, Et3SiH, CH2Cl2; aq. HF in MeCN) yielded N-acetyl-S-(2-cyano-2- hydroxy[D3]ethyl)cysteine. Monoprotection of [D4]ethylene glycol with tBuMe2SiCl and NaH in THF, oxidation to tBuMe 2SiOCD2CDO, conversion to tBuMe2SiOCD 2CD(OH)CN and tBuMe2SiOCD2CD(OTs)CN followed by nucleophilic substitution of the tosyloxy group with N-acetyl-L-cysteine (MeOD, Et3N) and deprotection with 4 M HCl in dioxane resulted in N-acetyl-S-(1-cyano-2-hydroxy[D3]ethyl)cysteine. All transformations (except the last but one) gave the respective products in good yields. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Belov, Vladimir N.,Korneev, Sergei M.,Angerer, Juergen,De Meijere, Armin
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scheme or table
p. 4417 - 4425
(2009/05/07)
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- Asymmetric synthesis of vicinal amino alcohols: Xestoaminol C, sphinganine and sphingosine
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The highly diastereoselective anti-aminohydroxylation of α,β-unsaturated esters, via conjugate addition of lithium (S)-N-benzyl-N-(α-methylbenzyl)amide and subsequent in situ enolate oxidation with (+)-(camphorsulfonyl)oxaziridine, has been used as the key step in the asymmetric synthesis of N,O-diacetyl xestoaminol C (41% yield over 8 steps), N,O,O-triacetyl sphinganine (30% yield over 8 steps) and N,O,O-triacetyl sphingosine (30% yield over 7 steps). The Royal Society of Chemistry 2008.
- Abraham, Elin,Davies, Stephen G.,Millican, Nicholas L.,Nicholson, Rebecca L.,Roberts, Paul M.,Smith, Andrew D.
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supporting information; experimental part
p. 1655 - 1664
(2008/10/09)
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- Asymmetric synthesis of 4-amino-γ-butyrolactones via lithium amide conjugate addition
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Upon treatment with homochiral lithium (R)-N-benzyl-N-(α-methylbenzyl)amide, γ-benzyloxy but-2-enoates undergo competitive conjugate addition and γ-deprotonation, while γ-tert-butyldimethylsilyloxy but-2-enoates undergo exclusive conjugate addition. Treatment of γ-benzyloxy or γ-tert-butyldimethylsilyloxy but-2-enamides with lithium (R)-N-benzyl-N-(α-methylbenzyl)amide furnishes exclusively the γ-benzyloxy- or γ-tert-butyldimethylsilyloxy-β-amino amide products of conjugate addition in high de. The γ-tert-butyldimethylsilyloxy-β-amino butanoate products of conjugate addition readily undergo O-desilylation and concomitant cyclisation to furnish 4-[N-benzyl-N-(α-methylbenzyl)amino]-γ-butyrolactone, which may be stereoselectively functionalised via deprotonation and alkylation?to give the corresponding trans-3-alkyl-4-amino-γ-butyrolactones. Alternatively, stereoselective alkylation of γ-benzyloxy- or γ-tert-butyldimethylsilyloxy-β-amino butanoates and butanamides through enolate formation and alkylation following a tandem (via the (Z)-lithium enolate) or stepwise (via the (E)-lithium enolate) protocol gives a range of separable syn- and anti-α-alkyl-β-amino esters and amides. O-Silyl deprotection of the syn- and anti-α-alkyl-β-amino butanoates with TBAF and concomitant cyclisation provide trans-3-alkyl-4-amino-γ-butyrolactones, consistent with epimerisation to the thermodynamically favoured trans-lactone occurring upon deprotection.
- Abraham, Elin,Cooke, Jason W.B.,Davies, Stephen G.,Naylor, Alan,Nicholson, Rebecca L.,Price, Paul. D.,Smith, Andrew D.
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p. 5855 - 5872
(2008/02/02)
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- A second-generation total synthesis of (+)-discodermolide: The development of a practical route using solely substrate-based stereocontrol
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(Chemical Equation Presented). A novel total synthesis of the complex polyketide (+)-discodermolide, a promising anticancer agent of sponge origin, has been completed in 7.8% overall yield over 24 linear steps, with 35 steps altogether. This second-genera
- Paterson, Ian,Delgado, Oscar,Florence, Gordon J.,Lyothier, Isabelle,O'Brien, Matthew,Scott, Jeremy P.,Sereinig, Natascha
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p. 150 - 160
(2007/10/03)
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- Catalytic enantioselective synthesis of quaternary all-carbon stereogenic centers. Preparation of α,α′-disubstituted β,γ-unsaturated esters through Cu-catalyzed asymmetric allylic alkylations
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(Chemical Equation Presented) Peptide-based chiral ligands, readily prepared from commercially available materials, are used to promote Cu-catalyzed asymmetric allylic alkylations of α,β-unsaturated esters bearing a γ-phosphate with various alkylzinc reagents. These transformations lead to the formation of α,α′-dialkyl-β,γ-unsaturated esters in high yields as well as high regio- (re) and enantloselectivities (ee).
- Murphy, Kerry E.,Hoveyda, Amir H.
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p. 1255 - 1258
(2007/10/03)
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- Decarboxylative aldol reactions of allyl β-keto Esters via heterobimetallic catalysis
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Mild and selective heterobimetallic-catalyzed decarboxylative aldol reactions involving allyl β-keto esters have been developed. The reaction is promoted by Pd(0)- and Yb(III)-DIOP complexes at room temperature and involves the in situ formation of a ketone enolate from allyl β-keto esters followed by addition of the enolate to aldehydes. The reaction is a new example of heterobimetallic catalysis in which the optimized reaction conditions require the addition of both metals. Copyright
- Lou, Sha,Westbrook, John A.,Schaus, Scott E.
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p. 11440 - 11441
(2007/10/03)
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- The synthesis of 5-hydroxy-3-methylnaphtho[2,3-c]furan-4,9-dione and 5,8-dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione
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5-Hydroxy-3-methylnaphtho[2,3-c]furan-4,9-dione (1), a metabolite isolated from Aloe ferox and Bulbine capitata, has been synthesized by a sequence involving an annulation reaction between the anion of 4-methoxy-3-oxo-1,3-dihydroisobenzofuran-1-carbonitrile (8) and (E)-pent-3-en-2-one, followed by subsequent construction of the furan ring through allylic bromination, hydrolysis, and dehydration as the key steps. The formation of several unusual products observed in annulation reactions between (8) and O-protected derivatives of (E)-5-hydroxypent-3-en-2-one (9) can be rationalized by invoking the intermediacy of a reactive o-quinone methide. 5,8-Dihydroxy-1-methylnaphtho[2,3-c]furan-4,9-dione (2), another naturally occurring naphtho[2,3-c]furan-4,9-dione, has been prepared by a Friedel-Crafts acylation of 1,4-dimethoxybenzene with 2-methylfuran-3,4-dicarbonyl dichloride. Arguments are presented that 5,8-dihydroxynaphtho[2,3-c]furan-4,9-dione is a better structural representation than the alternative 4,9-dihydroxynaphtho[2,3-c]furan-5,8-dione tautomer in such systems, as the latter would contain a reactive isobenzofuran moiety.
- Piggott, Matthew J.,Wege, Dieter
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p. 691 - 702
(2007/10/03)
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- Process for the oxidation of alcohols to aldehydes and ketones in the presence of nitroxyl compounds as catalysts
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An alcohol is oxidized to an aldehyde or a ketone in the presence of a nitroxyl compound as catalyst, wherein the alcohol to be oxidized is contained in an organic liquid phase, and is reacted in the presence of a nitroxyl compound with an aqueous phase comprising an oxidant. The reaction is carried out continuously at a contact time of the phases of from 0.1 s to a maximum of 15 minutes, with intensive mixing of the phases. The process produces high yields with low quantities of other oxidation byproducts.
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- Enantioselective total synthesis of the antitumor macrolide rhizoxin D
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The convergent, highly enantioselective synthesis of rhizoxin D, a natural product possessing potent antitumor and antifungal bioactivity, is described. The C(1)-C(9) fragment of the molecule was synthesized utilizing a threefold pseudosymmetric intermediate ultimately derived from γ-butyrolactone. The central core of rhizoxin D was prepared via a chiral resolution/asymmetric aldol protocol. Several methods for the generation of the polyene fragment were explored, and the side-chain was ultimately prepared from serine in six steps. The unification of the left and right wings of the molecule was achieved using a one-step olefination protocol, and the macrocyclization was carried out using a Horner-Emmons olefination at the C(2)-C(3) olefin.
- Lafontaine, Jennifer A.,Provencal, David P.,Gardelli, Cristina,Leahy, James W.
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p. 4215 - 4234
(2007/10/03)
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