- NOVEL CONNECTED BODY AND USE THEREOF IN SPECIFIC CONJUGATION BETWEEN BIOMOLECULE AND DRUG
-
PROBLEM TO BE SOLVED: To provide: a method for producing a connected body; a method for using the connected body in the production of a uniform conjugate; and a method for applying the conjugate in the treatment of cancer, infectious diseases, and autoimmune diseases. SOLUTION: A novel connected body is provided that includes a 2,3-di-substituted succinic acid group or a 2-mono-substituted or 2,3-di-substituted fumaric acid or maleic acid (trans (E)- or cis (Z)-butenedioic acid) group for conjugating 2 or more compounds/cytotoxic agents per connected body with a cell-binding molecule by specifically bridge-linking to a pair of thiol on the cell-binding molecule. The connected body is exemplified by the following general formula. SELECTED DRAWING: None COPYRIGHT: (C)2021,JPOandINPIT
- -
-
Paragraph 0237-0238
(2021/05/14)
-
- Thermal proteome profiling efficiently identifies ribosome destabilizing oxazolidinones
-
Identifying the targets of bioactive small molecules is a challenging endeavor for which no general solution currently exists. Classical affinity purification experiments suffer from the need to functionalise a bioactive compound and link it to a solid support, which may interfere with target binding. A modern mass spectrometry-based proteomics technique that has partially circumvented this problem is thermal proteome profiling (TPP), which determines the effect of an unmodified small molecule on the thermal stability of the whole proteome simultaneously. Here, we use TPP to identify the mode-of-action of a newly-discovered autophagy inhibitor based on oxazolidinones often employed as chiral auxiliaries. Surprisingly, a significant portion of all ribosomal proteins were found to be destabilized by the inhibitor, highlighting the utility of this technology for determining a challenging mode-of-action.
- N?cker, Christina,Kaiser, Nadine,Foley, Daniel,Sievers, Sonja,Janning, Petra,Waldmann, Herbert,Laraia, Luca
-
supporting information
(2021/04/22)
-
- EFFICIENT PREPARATION OF DOLASTATIN AND AURISTATIN ANALOGS THROUGH A COMMON INTERMEDIATE
-
Methods for making a dolastatin, auristatin or related compounds comprising the steps of providing a universal dolastatin core of Formula (I) reacting the C-terminal carboxylic acid group with an amine (A) to form an amide bond and reacting the N-terminal amine with a carboxylic acid (CA) to form an amide bond, wherein the steps can be performed in either order. Also provided are an isolated salt of the universal dolastatin core for use in preparation of dolastatins, auristatins and related compounds. Also provided are a number of intermediates and process steps which are useful for the preparation of high purity dolastatin core and high purity dolastatin and auristatin compounds.
- -
-
Paragraph 0084
(2021/09/17)
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- CONJUGATION LINKERS CONTAINING 2,3-DIAMINOSUCCINYL GROUP
-
Provided is a conjugate of a cytotoxic drug/molecule to a cell-binding molecule with a bis-linker (adual-linker) containing a 2, 3-diaminosuccinyl group. It also relates to preparation of the conjugate of a cytotoxic drug/molecule to a cell-binding molecule with the bis-linker, particularly when the drug having functional groups of amino, hydroxyl, diamino, amino-hydroxyl, dihydroxyl, carboxyl, hydrazine, aldehyde and thiol for conjugation with the bis-linker in a specific manner, as well as the therapeutic use of the conjugates.
- -
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Page/Page column 206
(2020/05/19)
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- CONJUGATION OF A CYTOTOXIC DRUG WITH BIS-LINKAGE
-
What provided is the conjugation of cytotoxic to a cell-binding molecule with a bis-linker(dual-linker) as shown in Formula (I). It provides bis-linkage methods of making a conjugate of a cytotoxic drug molecule to a cell-binding agent in a specific manner. It also relates to application of the conjugates for the treatment of a cancer, or an autoimmune disease, or an infectious disease.
- -
-
Paragraph 0689-0691
(2020/01/08)
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- CONJUGATION LINKERS, CELL BINDING MOLECULE-DRUG CONJUGATES CONTAINING THE LIKERS, METHODS OF MAKING AND USES SUCH CONJUGATES WITH THE LINKERS
-
The present invention relates to linkers having a group of propiolyl, substituted acryl (acryloyl), or disubstituted propanoyl, and using such linkers for the conjugation of compounds, in particular, cytotoxic agents to a cell-binding molecule.
- -
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Page/Page column 159; 160
(2018/05/27)
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- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
-
The present invention relates to an antibody-drug-conjugate or pharmaceutical composition comprising the same. From one aspect, the invention relates to an antibody-drug-conjugate (ADC) comprising an antibody consisting of the Trastuzumab or a biosimilar thereof, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment of cancer comprising administering to the subject an effective amount of said antibody-drug-conjugate or composition comprising the same.
- -
-
Paragraph 0243; 0244
(2017/05/15)
-
- COMPOSITION FOR THE TREATMENT OF IGF-1R EXPRESSING CANCER
-
The present invention relates to a method for the treatment of IGF-IR expressing cancers as well as to a compositions and a kit for said traitment. From one aspect, the invention reates to the combined use of a first antibody for the determination of the IGF-IR status of a cancer and a second antibody used as an ADC for the treatment of said cancer.
- -
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Page/Page column 104; 105
(2017/05/17)
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- SPECIFIC CONJUGATION LINKERS, SPECIFIC IMMUNOCONJUGATES THEREOF, METHODS OF MAKING AND USES SUCH CONJUGATES THEREOF
-
The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)- butenedioic), or acetylenedicarboxyl group for conjugation of a cytotoxic agent, and/or one or more different functional molecules per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
- -
-
Page/Page column 117
(2016/05/24)
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- CONJUGATE OF MONOMETHYL AURISTATIN F AND TRASTUZUMAB AND ITS USE FOR THE TREATMENT OF CANCER
-
The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody consisting of the Trastuzumab, said antibody being conjugated to at least one drug consisting of a monomethyl auristatin F derivative. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
- -
-
Page/Page column 33
(2016/11/17)
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- AURISTATIN ANALOGUES AND THEIR CONJUGATES WITH CELL-BINDING MOLECULES
-
This invention relates to analogues of auristatins, in particular monomethyl auristatin F (MMAF), as cytotoxic agents, conjugates of such cytotoxic agents with a cell-binding agent, the preparation and the therapeutic uses of these cytotoxic agents and conjugates thereof to arrest or retard abnormal cell growth and /or proliferation.
- -
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Page/Page column 6; 62
(2015/11/18)
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- NOVEL LINKERS AND THEIR USES IN SPECIFIC CONJUGATION OF DRUGS TO A BIOLOGICAL MOLECULE
-
The present invention relates to novel linkers containing a 2,3-disubstituted succinic group, or 2-monosubstituted, or 2,3-disubstituted fumaric or maleic (trans (E)- or cis (Z)- butenedioic) group for conjugation of two or more compounds/cytotoxic agents per linker to a cell-binding molecule, through bridge linking pairs of thiols on the cell-binding molecule specifically. The invention also relates to methods of making such linkers, and of using such linkers in making homogeneous conjugates, as well as of application of the conjugates in treatment of cancers, infections and autoimmune disorders.
- -
-
Page/Page column 93; 94
(2015/11/17)
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- IGF-1R ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
-
The present invention relates to an antibody-drug-conjugate capable of binding IGF-1R. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to IGF-1R, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug- conjugate for the treatment of cancer.
- -
-
Page/Page column 103
(2015/11/16)
-
- ANTIBODY-DRUG-CONJUGATE AND ITS USE FOR THE TREATMENT OF CANCER
-
The present invention relates to an antibody-drug-conjugate. From one aspect, the invention relates to an antibody-drug-conjugate comprising an antibody capable of binding to a Target, said antibody being conjugated to at least one drug selected from derivatives of dolastatin 10 and auristatins. The invention also comprises method of treatment and the use of said antibody-drug-conjugate for the treatment of cancer.
- -
-
Page/Page column 123; 124
(2015/11/10)
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- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
-
The present invention concerns a compound of following formula (I): where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: ■ a straight-chain or branched, saturated or unsaturated hydrocarbon group having 1 to 8 carbon atoms substituted by one or more groups chosen from among OH and NR5R6, ■ -(CH2CH2X1)(CH2CH2X2)a2(CH2CH2X3)a3(CH2CH2X4)a4(CH2CH2X5)a5R7, ■ an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or ■ a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
- -
-
Page/Page column 26
(2014/11/13)
-
- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
-
The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
- -
-
Page/Page column 19; 20
(2014/11/13)
-
- DERIVATIVES OF DOLASTATIN 10 AND AURISTATINS
-
The present invention concerns a compound of following formula (I) where: - R1 is H or OH, - R2 is a (C1-C6)alkyl, COOH, COO-((C1-C6)alkyl) or thiazolyl group, - R3 is H or a (C1-C6)alkyl group, and - R4 is: - an aryl-(C1-C8)alkyl group substituted by one or more groups chosen from among OH and NR9R10 groups, or - a heterocycle-(C1-C8)alkyl group optionally substituted by one or more groups chosen from among (C1-C6)alkyl, OH and NR12R13 groups, or a pharmaceutically acceptable salt, hydrate or solvate thereof, and its uses in particular for the treatment of cancer, pharmaceutical compositions containing the same and the preparation methods thereof.
- -
-
Page/Page column 22; 23
(2014/11/13)
-
- Asymmetric radical addition of TEMPO to titanium enolates
-
A mild method for a-hydroxylation of N-acyl oxazolidinones by asymmetric radical addition of the 2,2,6,6-tetramethylpiperidine N-oxy (TEMPO) radical to titanium enolates was developed. The high diastereoselectivity and broad scope of the reaction show synthetic utility for the a-hydroxylation of substrates that are not tolerant to strongly basic conditions.
- Mabe, Phillip J.,Zakarian, Armen
-
supporting information
p. 516 - 519
(2014/04/03)
-
- Synthesis of o -me ulongamide b and o -me ulongamide c, natural modified cyclodepsipeptides
-
Synthesis of O-Me ulongamide B and O-Me ulongamide C, modified natural cyclodepsipeptides, was achieved by a convergent route. The respective dipeptides and tridepsipeptides were coupled, obtaining linear depsipentapeptides, which were then deprotected and cyclized. These compounds were tested against three different types of human carcinoma cells and showed only moderate activity.
- Alvarado, Cuauhtémoc,Hernández, Gerardo,Díaz, Eduardo,Soano, José D.,Vilchis-Reyes, Miguel A.,Martínez-Urbina, Miguel A.,Guzmán, Angel
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p. 993 - 1006
(2013/03/13)
-
- Absolute configuration of lactams and oxazolidinones using kinetic resolution catalysts
-
A simple method for determining the absolute configuration of oxazolidinones, lactams, and their derivatives using kinetic resolution catalysts is described. The optically pure substrates were acylated using the (S)-HBTM and the (R)-HBTM catalyst, and the faster reaction was determined. An empirical mnemonic was developed for the assignment of the absolute configuration based on the fast-reacting catalyst.
- Perry, Matthew A.,Trinidad, Jonathan V.,Rychnovsky, Scott D.
-
supporting information
p. 472 - 475
(2013/04/11)
-
- Conformational preference in bis(porphyrin) tweezer complexes: A versatile chirality sensor for α-chiral carboxylic acids
-
Metallated porphyrin tweezers have demonstrated a remarkable ability to function as reporters of absolute stereochemistry for a number of different classes of organic molecules. Flexibility in binding, however, can result in an ensemble of different Exciton Coupled Circular Dichroism (ECCD) active conformations that could lead to variable results. Linker flexibility was found to be a key determinant of binding conformation. Experimental results indicate that a balance between linker flexibility and rigidity could yield an optimum porphyrin tweezer that stabilizes a common conformation for all bound chiral guests. This leads to a more simplified approach to absolute stereochemical determination of asymmetry for small organic molecules. This was demonstrated by the use of a C3-linked zincated porphyrin tweezer that yields a common conformational preference for a variety of α-chiral carboxylic acids derivatized with a diamine carrier. Copyright
- Tanasova, Marina,Borhan, Babak
-
supporting information; experimental part
p. 3261 - 3269
(2012/07/01)
-
- Chemoselective N-acylation of indoles and oxazolidinones with carbonylazoles
-
Unique reactivity: In the presence of more reactive amine and alcohol functional groups and of carboxylic acids, the chemoselective N-acylation of indoles (see scheme) and oxazolidinones is achieved by taking advantage of the unique reactivity of carbonylazole acylating agents with catalytic amounts of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Copyright
- Heller, Stephen T.,Schultz, Erica E.,Sarpong, Richmond
-
supporting information; experimental part
p. 8304 - 8308
(2012/09/08)
-
- Valence tautomerism in titanium enolates: Catalytic radical haloalkylation and application in the total synthesis of neodysidenin
-
(Chemical Equation Presented) A direct ruthenium-catalyzed radical chloroalkylation of N-acyl oxazolidinones capitalizing on valence tautomerism of titanium enolates has been developed. The chloroalkylation method served as the centerpiece in the enantioselective total synthesis of trichloroleucine-derived marine natural product neodysidenin.
- Beaumont, Stephane,Ilardi, Elizabeth A.,Monroe, Lucas R.,Zakarian, Armen
-
supporting information; experimental part
p. 1482 - 1483
(2010/04/03)
-
- SmI2-promoted intra- and intermolecular C-C bond formation with chiral N-acyl oxazolidinones
-
The suitability of chiral oxazolidinones in the SmI2-mediated C-C bond generation between the imide functionality of an N-acyl oxazolidinone unit and an olefinic radical acceptor, in both inter- and intramolecular reactions, was investigated. It was shown that the products from an Evans asymmetric alkylation can undergo direct carbon-carbon bond formation with an acrylamide providing chiral acyclic ketones in reasonable yields. These examples represent the first transformation of such N-acyl oxazolidinones where this chiral auxiliary is removed under the conditions for ketone formation. 5-exo-trig Cyclization studies were also undertaken with the same type of substrates, providing trans-2,5-disubstituted cyclopentanones in yields of approx. 50%. However, attempts to cyclize heteroatom-containing equivalents were less rewarding.
- Taaning, Rolf H.,Thim, Laura,Karaffa, Jacob,Campa?a, Araceli G.,Hansen, Anna-Mette,Skrydstrup, Troels
-
body text
p. 11884 - 11895
(2009/04/07)
-
- A study into asymmetric Nicholas cyclisation reactions
-
Three systematic approaches have been employed to investigate asymmetric Nicholas reactions. We found that the use of a chiral N-enoyl derivative provided acceptable levels of selectivity for an intermolecular Nicholas reaction, however, we were unable to identify an auxiliary that could be utilized in an asymmetric conjugate addition and a tandem inter/intramolecular series of Nicholas reactions. The use of chiral pool non-racemic propargyl alcohols, derived from citronellal, provided enhanced levels of selectivity. As a result of these studies we developed a series of Nicholas cyclisations derived from chiral non-racemic salicylaldehyde derivatives. These underwent an extremely rapid and highly efficient cyclisation, under Nicholas conditions, to afford a range of benzopyrans. The adjacent stereogenic centres appear to be formed with high levels of stereocontrol.
- Tyrrell, Elizabeth,Millet, Julien,Tesfa, Kibur Hunie,Williams, Neil,Mann, Alastair,Tillett, Caroline,Muller, Christophe
-
p. 12769 - 12778
(2008/03/28)
-
- Total synthesis of ulongamide A, a cyclic depsipeptide isolated from marine cyanobacteria Lyngbya sp.
-
A total synthesis of ulongamide A (1), a cytotoxic natural cyclic depsipeptide, was achieved by a convergent route involving coupling of the fragments 7 and 8 to the pentapeptide 24, and subsequent cyclization thereof after prior removal of the t-Boc protecting groups.
- Alvarado, Cuauhtémoc,Díaz, Eduardo,Guzmán, ángel
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p. 603 - 607
(2007/10/03)
-
- The preparation and reaction of enolates within micro reactors
-
Over the past 5 years, interest in the miniaturisation of chemical synthesis has grown rapidly, however in order to facilitate transfer of the technology from its current position as a research tool to industrial applications, a core understanding of the challenges associated with transferring reactions from the macro to the micro domain is required. This paper therefore aims to broach this problem by investigating the application of micro reactors to a range of commonly employed synthetic reactions including acylation, aldol, alkylation, 1,4-conjugate addition (Michael addition) and the Knoevenagel condensation. Comparison of the results obtained with traditional batch techniques enable us to highlight some of the advantages associated with micro reaction technology.
- Wiles, Charlotte,Watts, Paul,Haswell, Stephen J.,Pombo-Villar, Esteban
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p. 10757 - 10773
(2007/10/03)
-
- Total Syntheses of Amphidinolide T1, T3, T4, and T5
-
A concise, flexible, and high yielding entry into the family of amphidinolide T macrolides, a series of cytotoxic natural products of marine origin, has been developed. All individual members, except amphidinolide T3 (3), derive from compound 39 as a comm
- Aissa, Christophe,Riveiros, Ricardo,Ragot, Jacques,Fuerstner, Alois
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p. 15512 - 15520
(2007/10/03)
-
- Stereoselective synthesis of pamamycin-607
-
A macrodiolide antibiotic pamamycin-607 was synthesized by joining two hydroxy acid components. Three cis-2, 5-disubstituted tetrahydrofuran rings in the molecule were stereoselectively prepared by radical cyclization reactions of β-alkoxyvinyl ketone intermediates and a β-alkoxymethacrylate substrate. The key step of the synthesis is characterized by the predominant threo product formation in the radical cyclization reaction of a β-alkoxymethacrylate intermediate.
- Jeong, Eun Jeong,Kang, Eun Joo,Sung, Lee Taek,Hong, Sung Kil,Lee, Eun
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p. 14655 - 14662
(2007/10/03)
-
- A synthetic library of cell-permeable molecules
-
Small molecules that induce or stabilize the association of macromolecules have proven to be useful effectors of a wide variety of biological processes. To date, all examples of such chemical inducers of dimerization have involved known ligands to well-ch
- Koide,Finkelstein,Ball,Verdine
-
p. 398 - 408
(2007/10/03)
-
- Palladium-catalyzed intramolecular allylic alkylation reaction in marine natural product synthesis: Enantioselective synthesis of (+)-methyl pederate, a key intermediate in syntheses of mycalamides
-
A novel preparation of (+)-methyl pederate (4), a key intermediate in syntheses of mycalamides (1), marine natural products from a New Zeland sponge of the genus Mycale, is described. The key step involves palladium- catalyzed intramolecular allylic alkylation of the carbonate 21, derived from (+)-(4R,5R,E)-5-(tert-butyldimethylsiloxy)-4-methyl-2-hexenol (13), yielding lactones 5 in 87% yield. Demethoxycarbonylation of the cyclization products 5 and further functional group transformations led to (+)-methyl pederate (4).
- Toyota, Masahiro,Hirota, Masako,Nishikawa, Youichi,Fukumoto, Keiichiro,Ihara, Masataka
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p. 5895 - 5902
(2007/10/03)
-
- The dolastatins; 18: Stereospecific synthesis of dolaproine
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Dolastatin 10 (1), isolated from the sea hare Dolabella auricularia, has proved to be an exceptionally promising antineoplastic substance. Synthesis of this new and important peptide has been achieved. However, a more convenient and stereoselective synthesis of its three chiral center dolaproine (2a) unit has become necessary. A practical solution to this challenging problem was realized by employment of the following key reaction steps. Chiral oxazolidinone 5 was condensed at -75°C with S-prolinal 4 using dibutylboron triflate to direct the stereochemical course of the aldol reaction. Methylation of the product (6, 60-80% yields) and cleavage of the amide, in 83 and 93% yields respectively, completed a facile route to N-Boc-dolaproine (2b). Pertinent aspects of the aldol reaction and cleavage of oxazolidinone amides are discussed.
- Pettit, George R.,Burkett, Douglas D.,Barkóczy, József,Breneman, Gary L.,Pettit, William E.
-
p. 719 - 725
(2007/10/03)
-
- Enantioselective synthesis of 2-substituted 4-aminobutanoic acid (GABA) analogues via cyanomethylation of chiral enolates
-
Cyanomethylation by bromoacetonitrile of sodium or lithium enolates derived from (4S,5R)-3-acyl-4-methyl-5-phenyl-1,3-oxazolidin-2-ones usually shows good stereoselecrivity; although the reaction of 3-(3-carboxypropanoyl)oxazolidinone 5d is exceptionally
- Azam, Shamim,D'Souza, Alice A.,Wyatt, Peter B.
-
p. 621 - 627
(2007/10/03)
-
- Simple and efficient N-acylation reactions of chiral oxazolidinone auxiliaries
-
A simplified procedure for the N-acylation of oxazolidin-2-one chiral auxiliaries has been developed. The acylations occur at room temperature in the presence of triethylamine and catalytic quantities of 4-(N,N-dimethylamino)pyridine, thereby eliminating the necessity for a strong base such as butyllithium. Acylations with both symmetrical and mixed anhydrides, as well as acid chlorides, occur with a wide variety of oxazolidinone auxiliaries.
- Ager, David J.,Allen, David R.,Schaad, David R.
-
p. 1283 - 1285
(2007/10/03)
-
- Methods for the synthesis of L-leucine selectively labelled with carbon-13 or deuterium in either diastereotopic methyl group
-
A versatile approach is described for the enantioselective synthesis of isotopically labelled L-leucine involving the preparation of 4-methylpentanoic acid labelled selectively with carbon-13 or deuterium in either the pro-R or pro-S methyl group followed by a reductive amination of the ketone catalysed by leucine dehydrogenase. This strategy is applied to the total synthesis of (2S,4R)-[5,5,5-D3]-leucine using CD3I as the source of deuterium.
- Kelly,Kelly, Nicholas M.,Reid,Gordon Reid,Willis,Willis, Christine L.,Winton,Winton, Peter L.
-
p. 8315 - 8318
(2007/10/02)
-
- Stereocontrolled Synthesis of (2S,3S,8S,9S,4E,6E)-3-Amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic Acid (Adda), the Amino Acid Characteristic of Microcystins and Nodularin
-
(4R,5S)-4-Methyl-5-phenyloxazolidin-2-one has been used as a chiral template to construct the 8S and 9S chiral centres of (2S,3S,8S,9S)-3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca-4,6-dienoic acid (Adda), the 2S and 3S centres being derived from D-asp
- Beatty, Mark F.,Jennings-White, Clive,Avery, Mitchell A.
-
p. 1637 - 1642
(2007/10/02)
-
- Stereocontrolled Synthesis of a Key Lactone Intermediate Required for the Synthesis of Salinomycin
-
The stereocontrolled synthesis of lactone (1b), a key intermediate required for the synthesis of the polyether antibiotic salinomycin, is described.
- Brimble, Margaret A.
-
p. 1035 - 1046
(2007/10/02)
-
- Diastereoisomers of n6 -endo-bicyclo[2.2.1]heptyladenosine as antihypertensives with selective action
-
(1R-endo) or (1S-endo)-N-bicyclo[2.2.1]heptyl adenosine and pharmaceutically acceptable acid addition salts having highly desirable antihypertensive properties and unexpected A1 and A2 receptor binding activity, processes for their manufacture and pharmaceutical compositions and methods for using said compounds and compositions.
- -
-
-
- Convenient Preparation of Dimethyl -phosphonate
-
The diastereoselective alkylation of the chiral Evans intermediate 2 with 1-iodo-2-pentyne (3) gives the oxazolidinone 4.Titanium alkoxide-catalysed cleavage yields the ethyl ester 5, which is used to acylate dimethyl methanephosphonate to the chiral phos
- Harre, Michael,Trabandt, Joerg,Westermann, Juergen
-
p. 1081 - 1084
(2007/10/02)
-
- Erythro-Directive Reduction of α-Substituted Alkanones by Means of Hydrosilanes in Acidic Media
-
Hydrosilane reduced α-oxy and α-amino ketones and β-keto acid derivatives in trifluoroacetic acid to afford the corresponding erythro alcohols with high diastereoselectivity.The reaction proceeded without racemization at the carbon α to the carbonyl group.The erythro-directive reduction was explained in terms of the proton-bridged Cram cyclic model and successfully applied to the synthesis of physiologically important amino alcohols such as l-ephedrine, l-methoxamine, and erythro-2-methyl-3-piperidino-1-phenylpropanol.
- Fujita, Makoto,Hiyama, Tamejiro
-
p. 5415 - 5421
(2007/10/02)
-
- Ketene. Part 26. The Reactions of 3,4-Dihydroisoquinoline N-Oxide with Ketenes, and an Attempted Synthesis of 3,4-Dihydro-3,3-dimethylquinoline N-Oxide
-
3,4-Dihydroisoquinoline N-Oxide reacts with dimethylketene to form a 1:2 adduct (8) in addition to compounds (6) and (7).With cyano-t-butylketene and ethoxycarbonyl-t-butylketene the adducts (9a) and (9b) are formed. 3,3-Dimethyl-1,2,3,4-tetrahydroquinoline (21a) has been synthesized, but attempts to convert this into the nitrone (20b) were unsuccessful.
- Evans, Andrew R.,Martin, Russell,Taylor, Giles A.,Yap, C. H. Maurice
-
p. 1635 - 1640
(2007/10/02)
-
