- A Reverse Approach to the Total Synthesis of Halichondrin B
-
A new strategy is described for the total synthesis of halichondrin B featuring reversal of the sequential construction of a number of its cyclic ethers from the classical approach by instead forming C-O bonds first followed by C-C bond formation. Employing the Nicholas reaction to generate linear ethers as precursors for the total synthesis of halichondrin B and other members of the halichondrin and eribulin families of compounds, this novel approach provides new opportunities for the development of improved syntheses of these complex and valuable compounds. In this Article, we report the syntheses of defined fragments I, MN, EFG, and A. Fragments I and MN were then coupled and elaborated to advanced intermediate IJKLMN, which was joined with fragment EFG to afford, after appropriate elaboration and macrolactonization, the more advanced polycyclic intermediate EFGHIJKLMN. Elaboration of the latter and coupling with fragment A followed by further functionalization completed the total synthesis of halichondrin B through a short and convergent pathway.
- Nicolaou,Pan, Saiyong,Shelke, Yogesh,Das, Dipendu,Ye, Qiuji,Lu, Yong,Sau, Susanta,Bao, Ruiyang,Rigol, Stephan
-
supporting information
p. 9267 - 9276
(2021/07/01)
-
- METHOD FOR SYNTHESIZING A PRECURSOR OF A SINGLE DAIRY-LACTONE ISOMER
-
This disclosure provides a method for preparing a precursor of a single dairy-lactone isomer, methods of preparing a single dairy-lactone isomer, and to the organoleptic uses thereof.
- -
-
-
- Palladium-Catalyzed Atom-Transfer Radical Cyclization at Remote Unactivated C(sp3)?H Sites: Hydrogen-Atom Transfer of Hybrid Vinyl Palladium Radical Intermediates
-
A novel mild, visible-light-induced palladium-catalyzed hydrogen atom translocation/atom-transfer radical cyclization (HAT/ATRC) cascade has been developed. This protocol involves a 1,5-HAT process of previously unknown hybrid vinyl palladium radical intermediates, thus leading to iodomethyl carbo- and heterocyclic structures.
- Ratushnyy, Maxim,Parasram, Marvin,Wang, Yang,Gevorgyan, Vladimir
-
p. 2712 - 2715
(2018/03/02)
-
- Chiral hypervalent iodine(III) catalyst promotes highly enantioselective sulfonyl-and phosphoryl-oxylactonizations
-
An efficient enantioselective hypervalent iodine promoted oxylactonization of 4-pentenoic acids has been achieved using stoichiometric or a catalytic amount of chiral aryl-λ3-iodane. This reaction provides straightforward access to a wide range of sulfonyloxy-and phosphoryloxy-γ-butyrolactones in respectable yields with moderate to excellent enantioselectivities.
- Gelis, Coralie,Dumoulin, Audrey,Bekkaye, Mathieu,Neuville, Luc,Masson, Géraldine
-
p. 278 - 281
(2017/11/27)
-
- Chemo-enzymatic synthesis of chiral epoxides ethyl and methyl (S)-3-(Oxiran-2-yl)propanoates from Renewable levoglucosenone: An access to enantiopure (S)-dairy lactone
-
Chiral epoxides-such as ethyl and methyl (S)-3-(oxiran-2-yl)propanoates ((S)-1a/1b)-are valuable precursors in many chemical syntheses. Until recently, these compounds were synthesized from glutamic acid in four steps (deamination, reduction, tosylation and epoxide formation) in low to moderate overall yield (20%-50%). Moreover, this procedure requires some harmful reagents such as sodium nitrite ((eco)toxic) and borane (carcinogen). Herein, starting from levoglucosenone (LGO), a biobased chiral compound obtained through the flash pyrolysis of acidified cellulose, we propose a safer and more sustainable chemo-enzymatic synthetic pathway involving lipase-mediated Baeyer-Villiger oxidation, palladium-catalyzed hydrogenation, tosylation and treatment with sodium ethoxide/methoxide as key steps. This route afforded ethyl and methyl (S)-3-(oxiran-2-yl)propanoates in 57% overall yield, respectively. To demonstrate the potentiality of this new synthetic pathway from LGO, the synthesis of high value-added (S)-dairy lactone was undertaken from these epoxides and provided the target in 37% overall yield from LGO.
- Peru, Aurélien A. M.,Flourat, Amandine L.,Gunawan, Christian,Raverty, Warwick,Jevric, Martyn,Greatrex, Ben W.,Allais, Florent
-
-
- HETEROCYCLIC COMPOUNDS AND THEIR USE AS RETINOID-RELATED ORPHAN RECEPTOR (ROR) GAMMA-T INHIBITORS
-
Provided are heterocyclic compounds having a RORγt inhibitory action represented by the formula (I): wherein each symbol is as defined in the specification, or a salt thereof.
- -
-
Paragraph 0346
(2016/01/25)
-
- PYRIMIDINE AND TRIAZINE DERIVATIVES AND THEIR USE AS AXL INHIBITORS
-
Compounds of the general formula(I): (I) processes for the preparation of these compounds, compositions containing these compounds, and the uses of these compounds.
- -
-
Page/Page column 95
(2016/07/05)
-
- PYRAZOLE AMIDE DERIVATIVE
-
The present invention relates to a novel compound having a function of inhibiting RORγ activity. The present invention also relates to pharmaceutical composition comprising the compound, a use of the compound in treating or preventing autoimmune diseases, inflammatory diseases, metabolic diseases, or cancer diseases.
- -
-
Page/Page column 91; 92
(2015/09/28)
-
- Stereochemical elucidation of streptorubin B
-
Streptorubin B is a structurally remarkable mem-ber of the prodiginine group of antibiotics produced by several actinobacteria, including the model organism Streptomyces coelicolor A3(2). Transannular strain within the pyrrolophane structure of this molecule causes restricted rotation that gives rise to the possibility of (diastereomeric) atropisomers. Neither the relative nor the absolute stereochemistry of streptorubin B is known. NOESY NMR experiments were used to define the relative stereochemistry of the major atropisomer of streptorubin BHCl in solution as anti. We exploited this finding together with our knowledge of streptorubin B biosynthesis in S. coelicolor to determine the absolute stereochemistry of the anti atropisomer. 2-Undecylpyrrole stereoselectively labeled with deuterium at C-4′ was synthesized and fed to a mutant of S. coelicolor, which was unable to produce streptorubin B because it was blocked in 2-undecylpyrrole biosynthesis, and in which the genes responsible for the last two steps of streptorubin B biosynthesis were overexpressed. 1H and 2H NMR analysis of the stereoselectively deuterium-labeled streptorubin BHCl produced by this mutasynthesis strategy allowed us to assign the absolute stereochemistry of the major (anti) atropisomer as 7′S. HPLC analyses of streptorubin B isolated from S. coelicolor on a homochiral stationary phase and comparisons with streptorubin B derived from an enantioselective synthesis showed that the natural product consists of an approximately 88:7:5 mixture of the (7′S, anti), (7′S, syn), and (7′R, anti) stereoisomers.
- Haynes, Stuart W.,Sydor, Paulina K.,Corre, Christophe,Song, Lijiang,Challis, Gregory L.
-
p. 1793 - 1798
(2011/04/12)
-
- Synthesis of azide-alkyne fragments for "Click" chemical applications. Part 2. Formation of oligomers from orthogonally protected chiral trialkylsilylhomopropargyl azides and homopropargyl alcohols
-
(Chemical Equation Presented) A small library of chiral, β3-substituted homopropargyl alcohols and chiral β3-substituted trimethylsilylhomopropargyl azides were generated starting from natural L-amino acids. The free alkynes and azides were then coupled, using a Huisgen 1,3-dipolar cycloaddition, to provide chiral oligomeric 1,4-disubstituted-1,2,3-triazoles as potential peptidomimetic compounds. The work is an extension to the previous synthesis of racemic, orthogonally protected 1,4-disubstituted-1,2,3-triazoles from the corresponding α-substituted propargyl alcohols and α-substituted trialkylsilylpropargyl azides.
- Montagnat, Oliver D.,Lessene, Guillaume,Hughes, Andrew B.
-
scheme or table
p. 390 - 398
(2010/03/30)
-
- NOVEL COMPOUNDS AS CANNABINOID RECEPTOR LIGANDS AND USES THEREOF
-
The present invention relates to compounds of formula (I), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1, R2, R3, and L1 are defined in the specfication, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions. The present invention also relates to compounds of formula (II), or pharmaceutical salts, prodrugs, salts of prodrugs, or combinations thereof, wherein R1a, R2a and (Rx)n are as defined in the specification, compositions comprising such compounds, and methods of treating conditions and disorders using such compounds and compositions.
- -
-
Page/Page column 67
(2008/06/13)
-
- Probing the importance of the hemilabile site of bis(phosphine) monoxide ligands in the copper-catalyzed addition of diethylzinc to N-phosphinoylimines: Discovery of new effective chiral ligands
-
(Chemical Equation Presented) The hemilabile ligand Me-DuPHOS(O) 2 has proven to be a successful ligand for the copper-catalyzed addition of diethylzinc to N-phosphinoylimines. The corresponding α-chiral amines were obtained in high yields (80-98%) and enantiomeric ratios (19.0:1 to 99.0:1 er). Furthermore, this Cu?2 catalytic system has been shown to be effective in the addition of diethylzinc to nitroalkenes and in the reduction of β,β-disubstituted vinyl phenyl sulfones. This paper describes a general structure/selectivity study in which the three ligand subunits (chiral phospholane-linker-labile coordinating group (Z)) are systematically modified and tested in the copper-catalyzed addition of diethylzinc to the N-phosphinoylimine 1 derived from benzaldehyde. This study led to the discovery of a new class of effective chiral ligands that combine a chiral phospholane unit and an achiral phosphine oxide.
- Bonnaventure, Isabelle,Charette, Andre B.
-
p. 6330 - 6340
(2008/12/22)
-
- Total synthesis and structural confirmation of (+)-longicin
-
(Chemical Equation Presented) A stereocontrolled total synthesis of (+)-longicin, a representative of the class of mono-THF-acetogenins, is described. The strategy involves the utilization of D- and L-glutamic acids as chirons that correspond to two five-carbon segments harboring stereogenic centers at C4 and at C17 of the C32 polyketide-derived natural product. The use of Grubbs' RCM reaction as a novel "chain elongation" strategy for the synthesis of acetogenin-type structures and a new protocol for butenolide incorporation are also described.
- Hanessian, Stephen,Giroux, Simon,Buffat, Maxime
-
p. 3989 - 3992
(2007/10/03)
-
- Synthesis of (-)-amphidinolide K fragment C9-C22
-
(Chemical Equation Presented) The key fragment (2a or 2b) in a total synthesis of the cytotoxic macrolide (-)-amphidinolide K (1) has been achieved from synthons C9-C14 (3) and C15-C22 (4), which have both been prepared from glutamic acid in good overall yields.
- Andreou, Thanos,Costa, Anna M.,Esteban, Laia,Gonzalez, Lluisa,Mas, Gemma,Vilarrasa, Jaume
-
p. 4083 - 4086
(2007/10/03)
-
- Two approaches to the enantioselective synthesis of (4R)-(-)-4-hydroxymethyl-4-thiobutyro-1,4-lactone
-
Enantiomerically pure (4R)-4-hydroxymethyl-4-thiobutyro-1,4-lactone [(5R)-dihydro-5-(hydroxymethyl)-2(3H)-thiophenone (12)] and derivatives were synthesized by two enantiospecific sequences employing D-ribono-1,4-lactone (1) and L-glutamic acid (6) as chiral templates. The key step in the first approach was the SmI2-promoted 2,3-deoxygenation of a 4-thio-L-lyxono-1,4-lactone derivative, prepared from 1. The other strategy, which starts from 6, involves the (5S)-dihydro-5-(p-tolylsulfonyloxymethyl)-2-(3H)-furanone (8) as chiral precursor. This was converted into a 4,5-thiirane derivative via the corresponding 4,5-epoxide. Regioselective opening of the thiirane ring by acetate followed by O-deacetylation gave 12 (40% overall yield from 8). Copyright (C) 2000 Elsevier Science Ltd.
- Zunszain, Patricia A.,Varela, Oscar
-
p. 765 - 771
(2007/10/03)
-
- Synthesis and absolute stereochemistry of Hagen's-Gland lactones in some parasitic wasps (Hymenoptera:Braconidae)
-
Efficient syntheses and enantioselective gas chromatography have confirmed the structures and established the absolute stcreochemistry of some novel bicyclic lactones (tetrahydrofurofuranones) in species of parasitic wasps (Hymenoptera:Braconidae). The co-occurring γ-lactones, octan-4-olide and dodecan-4-olide, have the (R)-configuation.
- Paddon-Jones, Gregory C.,Moore, Christopher J.,Brecknell, Douglas J.,Koenig, Wilfried A.,Kitching, William
-
p. 3479 - 3482
(2007/10/03)
-
- Synthesis of C1-C11 fragment of annonacin: A polyketide acetogenin of Annonaceae
-
(4R, 10S)-Methyl tri-isopropylsilyloxy-4-tert-butyldimethylsilyloxy-10-tert-amyloxy-11- undecanoate 1 has been synthesized from L-glutamic acid. This compound is a key intermediate in the total synthesis of annonacin, an acetogenin of Annonaceae.
- Figadere,Franck,Cave
-
p. 1637 - 1640
(2007/10/02)
-
- Enantioenriched N-(2-Chloroalkyl)-3-acetoxypiperidines as Potential Cholinotoxic Agents. Synthesis and Preliminary Evidence for Spirocyclic Aziridinium Formation.
-
The syntheses of six enantioenriched analogs representing cyclic forms of acetylcholine are reported. (S)- and (R)-N-(2-chloroethyl)-3-acetoxypiperidine and (R,R)-, (R,S)-, (S,R)-, and (S,S)-N-(2-chloropropyl)-3-acetoxypiperidine have been synthesized from (R)- or (S)-3-hydroxypiperidine in five steps. (R)- and (S)-3-hydroxypiperidine were accessed via parallel stereospecific routes from d- and l-glutamic acid, and through fractional recrystallization of diastereomeric tartranilic acid salts. (S)-N-(2-Chloroethyl)-3-acetoxypiperidine was reacted with silver perchlorate to form a spirocyclic aziridinium analog of acetylcholine as evidenced by a characteristic 1H NMR shift for the aziridinium methylene groups.
- Huh, Nam,Thompson, Charles M.
-
p. 5935 - 5950
(2007/10/02)
-
- Asymmetric synthesis of enantiopure (+)-(1S,2S) methyl 2-formylcyclopropanecarboxylate and corresponding (Z) and (E) didehydroamino acid derivatives
-
The title cyclopropane aldehyde and didehydroamino acids have been synthesised from (S)-(+)-γ-butyrolactone-γ-carboxylic acid as a chiral precursor.
- Le Corre,Hercouet,Bessieres
-
p. 683 - 684
(2007/10/02)
-
- A synthetic approach to the pseudopterosins using cascade technology
-
A rapid synthetic entry towards the pseudopterosins, a class of diterpenes which display potent anti-inflammatory and analgesic properties, is described. The key feature of this approach is the use of a sequential intramolecular, Lewis acid mediated Friedel-Crafts alkylation - Friedel-Crafts acylation sequence, viz 14 to 15, to establish the tricyclic carbon framework.
- Harrowven,Harrowven, David C.,Dennison,Dennison, Shelagh T.,Howes,Howes, Peter
-
p. 4243 - 4246
(2007/10/02)
-
- Enantiospecific Preparation of the Lactone Fragment of Murisolin
-
Both enantiomers (R) and (S) of the functionalized unsaturated γ-lactone moiety of the acetogenin murisolin have been enantiospecifically synthezised from L and D-glutamic acid respectively.
- Harmange, Jean-Christophe,Figadere, Bruno,Hocquemiller, Reynald
-
p. 347 - 350
(2007/10/02)
-
- TOTAL SYNTHESIS OF 5(S),12(S)- AND 5(S),12(R)-DIHYDROXYEICOSA-6(Z),8(E),14(Z)-TRIENOIC ACIDS, METABOLITES OF LEUKOTRIENE B4
-
The recently identified dihydro-leukotriene B4 metabolite 1 and its C(12)-epi analogue 2 were prepared by Wittig coupling of segments derived from 2-deoxy-D-ribose and L-glutamic acid.
- Yadagiri, Pendri,Lumin, Sun,Falck, J. R.
-
p. 429 - 432
(2007/10/02)
-
- Synthesis of New Optically Active Bis- and Tris(phosphines)
-
The synthesis of new optically active alkanediylbis- and alkanetriyltris(diphenylphosphines) is described.Easily accessible optically pure lactones and carboxylic acids are reduced to the alcohols, tosylated and reacted with lithium diphenylphosphide to give the corresponding phosphines.
- Brunner, Henri,Lautenschlager, Hans-Juergen
-
p. 706 - 709
(2007/10/02)
-
- The Synthesis of (+)- and (-)-t-Butyl Nonactate from L-Glutamic Acid
-
A short enantiodivergent route to (+)- and (-)-t-butyl nonactate (2b) from lactone (3) is described; a method for determining the optical purity of these compounds which can be used to resolve (+/-)-methyl nonactate (2c) is reported.
- Batmangherlich, Shari,Davidson, Alan H.
-
p. 1399 - 1401
(2007/10/02)
-
- L'ELDANOLIDE, PHEROMONE DES GLANDES ALAIRES DE LA PYRALE DE LA CANNE A SUCRE, ELDANA SACCHARINA (WLK.): STRUCTURE ET SYNTHESE DE SES DEUX ENANTIOMERES
-
The isolation and structure determination of eldanolide, the wing gland pheromone of the male African Sugar Cane Borer, Eldana saccharina (Wlk.) is described.The absolute configuration was determined as (3S, 4R) by comparison of the CD spectra of the natural pheromone with both synthetic enantiomers.
- Vigneron, J. P.,Meric, R.,Larcheveque, M.,Debal, A.,Lallemand, J. Y.,et al.
-
p. 3521 - 3530
(2007/10/02)
-
- A Facile and General Entry to Optically Active Pheromones and Aromas With γ-Alkyl-γ-lactone Structures. A Study of Some Lactone Derivatives of Pentoses
-
A new and easy general methodology has been developed to prepare γ-alkyl-α,β-butenolides or γ-alkylbutyrolactones in four and five steps, respectively, from D-ribonolactone as a common chiral starting material.Some of these products have pheromonal activity in insects and are also used as fruit fragrances.A study on several derivatives of D-ribonolactone and 2-deoxy-D-ribonolactone has been carried out in order to explore alternative routes for these syntheses.
- Cardellach, J.,Font, J.,Ortuno, R. M.
-
p. 327 - 331
(2007/10/02)
-
- AN ASYMMETRIC SYNTHESIS OF CIS, ANTI, CIS-TRICYCLO2,6>DECANES APPLYING γ-HYDROXYMETHYL-γ-BUTYROLACTONE AS A CHIRAL SYNTHON. FIRST ASYMMETRIC TOTAL SYNTHESIS OF (-)-β-BOURBONENE
-
The asymmetric total synthesis of cis, anti, cis-tricyclo2,6>decane sesquiterpene β-bourbonene is described.The key (2+2) photocycloaddition was carried out applying the optically pure butenolide derivative 6b as a chiral synthon.
- Tomioka, Kiyoshi,Tanaka, Masahide,Koga, Kenji
-
p. 3401 - 3404
(2007/10/02)
-
- Preparation of 3-Deoxy-aldonolactones by Hydrogenolysis of Acetylated Aldonolactones
-
Acetylated aldono-1,4-lactones, when treated with hydrogen in the presence of triethylamine and palladium on carbon, form acetylated 3-deoxy-aldono-1,4-lactones in high yield through elimination of the 3-acetoxy group and subsequent stereospecific hydrogenation of the unsaturated intermediate.Thus, acetylated D-galactono-1,4-lactone (1) yields tri-O-acetyl-3-deoxy-D-xylo-hexono-1,4-lactone (3a).Acetylated D-mannono- or D-glucono-1,4-lactone both give 3-deoxy-D-arabino-hexono-1,4-lactone (10a), whereas the four acetylated D-pentono-1,4-lactones (14-17) all afford di-O-acetyl-D-threo-pentono-1,4-lactone (18a).D-Gluconolactone can be converted into (R)-γ-caprolactone (27) on treatment with hydrogen bromide followed by a series of reductions.Similarly, D-lyxonolactone produces 2,3-dideoxy-D-glycero-pentono-1,4-lactone (29).
- Bock, Klaus,Lundt, Inge,Pedersen, Christian
-
p. 155 - 162
(2007/10/02)
-