- An improved synthesis of the C15-C28 fragment of laulimalide
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The C15-C28 fragment of the paclitaxel-like antimicrotubule agent laulimalide has been synthesized in 12 linear steps from known epoxide 5, with an overall yield of 16%. The methyldihydropyran ring of the side chain was efficiently prepared using ring-closing olefin metathesis chemistry. The 19,20-diol stereochemistry originates in starting material 7 and the side chain was appended using a Kocienski-modified Julia coupling.
- Sivaramakrishnan,Nadolski, Geoffry T.,McAlexander, Ian A.,Davidson, Bradley S.
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Read Online
- Enantioselective synthesis of fatty acid amide hydrolase inhibitors with 1, 3-disubstituted butan-2-one scaffold
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Fatty acid amide hydrolase is a key enzyme in the inactivation of the analgesic and anti-inflammatory endocannabinoid anandamide. Previously, the chiral compound 1-(1H-benzotriazol-1-yl)-3-(4-phenylphenoxy)butan-2-one was identified as a potent inhibitor of fatty acid amide hydrolase and is therefore of interest as a potential agent against pain and inflammation. Two different approaches for the enantioselective synthesis of fatty acid amide hydrolase inhibitors with a 1, 3-disubstituted butan-2-one scaffold were carried out. The first one uses the chiral epoxide 2-[1-(4-phenylphenoxy)ethyl]oxirane with an (R)- or (S)-configuration at the exocyclic stereocenter as central intermediates. These substances were obtained by separation of the non-stereoselectively synthesized epoxide into its racemic diastereomers by reversed phase chromatography followed by Jacobsen's hydrolytic kinetic resolution of each enantiomer with the (S)-configured oxirane ring. Furthermore, a chiral pool based enantioselective synthesis was developed. In that case, the starting compound for both target enantiomers was methyl 3, 4-O-isopropylidene-L-threonate. In comparison to the first approach, the chiral pool synthesis consisted of more steps, but generated the enantiomers with much better enantiomeric excess. Biological evaluation showed that the (R)-enantiomer inhibits isolated fatty acid amide hydrolase with a 200-fold higher activity than the (S)-enantiomer.
- Sundermann, Tom R.,Lehr, Matthias
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supporting information
p. 447 - 453
(2017/03/24)
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- Packaging comprising forms of sodium salt of 4-tert-butyl-N-[4-chloro-2-(1-oxy-pyridine-4-carbonyl)-phenyl]-benzenesulfonamide
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The invention relates to a packaging comprising a multitude (A) of at least 2 administration units comprising polymorphic trihydrated forms of sodium salt of 4-tert-butyl-N-[4-chloro-2-(1-oxy-pyridine-4-carbonyl)-phenyl]-benzenesulfonamide; or (B) of at least 2 administration units comprising polymorphic solvated or desolvated forms of sodium salt of 4-tert-butyl-N-[4-chloro-2-(1-oxy-pyridine-4-carbonyl)-phenyl]-benzenesulfonamide.
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Paragraph 0045
(2016/08/29)
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- N- (6- ( (2R,3S) -3,4-DIHYDROXYBUTAN-2-YLOXY) -2- (4 - FLUOROBENZYLTHIO) PYRIMIDIN- 4 - YL) -3- METHYLAZETIDINE- 1 - SULFONAMIDE AS CHEMOKINE RECEPTOR MODULATOR
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There is provided a compound which is (a) a pyrimidine sulfonamide of formula (I) or (b) a pharmaceutically acceptable salt thereof, crystalline forms of the compound, processes for obtaining the compound, pharmaceutical intermediates used in the manufacture of the compound, and pharmaceutical compositions containing the compound. The compound is useful in the treatment of a disease/condition in which modulation of chemokine receptor activity is beneficial.
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Page/Page column 42; 43
(2013/03/26)
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- CRYSTALLINE FORMS OF N-[2-[[(2,3-DIFLUOROPHENYL)METHYL]THIO]-6--4-PYRIMIDINYL]-1-AZETIDINESULFONAMIDE
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There is provided crystalline forms of N-[2-[[(2,3-difluorophenyl)methyl]thio]-6-{[(1R,2S)-2,3-dihydroxy-1-methylpropyl]oxy}-4-pyrimidinyl]1-azetidinesulfon-amide anhydrate. Such compounds/forms may be useful in the treatment of a disease/condition in which modulation of chemokine receptor activity is beneficial.
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Page/Page column 9
(2012/02/01)
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- From L-ascorbic acid to protease inhibitors: Practical synthesis of key chiral epoxide intermediates for aspartyl proteases
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Efficient synthetic routes were developed to prepare a sizable amount (4-15 grams) of the chiral epoxides 4-6 as versatile intermediates for the synthesis of aspartyl protease inhibitors of therapeutic interest such as HIV protease and β-secretase. Oxidative cleavage of the C(2)-C(3) double bond of L-ascorbic acid followed by functional group manipulation led to the preparation of the epoxide 10, which was opened with an azide to yield a common aziridine intermediate 12. Through opening of the aziridine ring of 12 with either a carbon or a sulfur nucleophile, chiral epoxide precursors 4-6 could be prepared for various HIV protease inhibitors. Except for the final low melting epoxides 5 and 6, all intermediates were obtained as crystalline solids, thus the synthetic pathway can be easily applied to a large-scale synthesis of the chiral epoxides.
- Chang, Sun Ki,So, Soon Mog,Lee, Sang Min,Kim, Min Kyu,Seol, Kyoung Mee,Kim, Sung Min,Kang, Jae Sung,Choo, Dong Joon,Lee, Jae Yeol,Kim, B. Moon
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p. 2213 - 2218
(2012/09/21)
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- First stereoselective total synthesis of panaxjapyne C
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The first stereoselective total synthesis of polyacetylene panaxjapyne C is described. The key reactions include regioselective opening of the epoxide and Cadiot-Chodkiewicz cross-coupling reactions. l-Ascorbic acid was used as a chiral pool material for the construction of the both terminal acetylenes.
- Thakur, Pallavi,Kumaraswamy,Raji Reddy,Bandichhor, Rakeshwar,Mukkanti
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scheme or table
p. 3703 - 3705
(2012/09/21)
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- Total synthesis of (+)-obtusenyne
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The stereoselective total synthesis of (+)-obtusenyne is described. The oxonene skeleton possessing trans-orientated alkyl substituents at the α,α′-positions was stereoselectively constructed via cyclization of the corresponding hydroxy epoxide promoted b
- Uemura, Toshiyuki,Suzuki, Toshio,Onodera, Naohiro,Hagiwara, Hisahiro,Hoshi, Takashi
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p. 715 - 719
(2007/10/03)
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- Stereoselective total synthesis of microcarpalide
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A stereoselective total synthesis of microcarpalide using ring-closing metathesis (RCM) as a key step is reported. l-Ascorbic acid was used as a chiral pool material for the construction of the olefinic alcohol and an asymmetric aldol reaction provided the chiral precursor for the synthesis of olefinic acid.
- Sharma,Cherukupalli, Govardhan R.
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p. 1081 - 1088
(2007/10/03)
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- Polyol synthesis through hydrocarbon oxidation: De novo synthesis of L-galactose
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(Chemical Equation Presented) Carbohydrates from hydrocarbons : A hydrocarbon oxidation strategy for the synthesis of chiral polyols is validated by the enantioselective, de novo synthesis of differentially protected L-galactose (see scheme, TBS = tert-bu
- Covell, Dustin J.,Vermeulen, Nicolaas A.,Labenz, Nathan A.,White, M. Christina
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p. 8217 - 8220
(2008/02/09)
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- A new efficient and practical synthesis of 2-deoxy-L-ribose
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An efficient and practical route for large-scale synthesis of 2-deoxy-l-ribose starting from l-ascorbic acid was developed in eight steps without chromatographic purification for all intermediates. Additionally, (2S,3R)-3,4-epoxy-1,2-O-isopropylidenebutane-1,2-diol, a versatile intermediate in carbohydrate synthesis, was also prepared readily in excellent yield as a key intermediate.
- Cho, Bong Hwan,Kim, Jin Hwan,Jeon, Heung Bae,Kim, Kwan Soo
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p. 4341 - 4346
(2007/10/03)
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- Synthesis of the 1,4-diazepan-2-one moiety of liposidomycins
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The two stereoisomers 12 and 16 of 1,4-dimethyl-1,4-diazepan-2-one, a central feature of liposidomycins, have been synthesized starting from L-ascorbic acid and sarcosine.
- Kim, Kwan Soo,Cho, In Haeng,Ahn, Yeong Hee,Park, Jong Ii
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p. 1783 - 1786
(2007/10/02)
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- ERYTHRITOL : A VERSATILE PRECURSOR FOR C-4 CHIRAL BUILDING BLOCKS
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Starting from erythritol, enzyme catalyzed construction of C4 chiral building blocks is described.The four diastereomeric protected tetroses are available from this single compound.Also an approach to L- and D-hexose-derivatives is presented.
- Pottie, M.,Lathauwer, G. De,Vandewalle, M.
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p. 285 - 294
(2007/10/02)
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- Total Synthesis of (2S,3S,4R)-2--16-methylheptadecane-1,3,4-triol 3,4-dibenzoate, a Partially Protected Ceramide Part of Sponge Cerebrosides
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(2S,3S,4R)-2--16-methylheptadecane-1,3,4-triol 3,4-dibenzoate 32, apertially protected ceramide part of a cerebroside from the marine sponge Halichondria japonica, has been synthesized from L-ascorbic acid, and its absolute stereochemistry has been determined.The key steps in the synthesis include the regioselective ring opening of chiral epoxide 5 with a 2-alkyl-2-lithio-1,3-dithiane and the introduction of a hydroxymethylene synthon using Dondoni's protocol to assemble C(1) and C(2) functionality.
- Nakashima, Hideki,Hirata, Norihiko,Iwamura, Takeru,Yamagiwa, Yoshiro,Kamikawa, Tadao
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p. 2849 - 2858
(2007/10/02)
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- The Synthesis of Optically Active Derivatives of Erythritol
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The acetonides 2 and 4, obtained from erythritol, are excellent substrates for SAM II lipase.The resulting homochiral mono-esters 3 and 5 are suitable chiral building blocks.
- Pottie, M.,Eycken, J. Van der,Vandewalle, M.
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p. 329 - 330
(2007/10/02)
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- CHIRAL α-HYDROXY- AND α,β-DIHYDROXY-ALDEHYDES FROM D-ISOASCORBIC AND L-ASCORBIC ACIDS. USEFUL PRECURSORS FOR THE SYNTHESIS OF FATTY ACID METABOLITES.
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The four possible stereoisomers of α,β-dihydroxyaldehydes, useful building blocks for the synthesis of fatty acids metabolites, are synthesized via epoxy-tetrols derived from D-isoascorbic and L-ascorbic acids.The general method we develop allows the synthesis of chiral α-hydroxyaldehydes as well.
- Merrer, Y. Le,Gravier-Pelletier, C.,Dumas, J.,Depezay, J. C.
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p. 1002 - 1006
(2007/10/02)
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- Synthesis of Chiral Long-chain α-Hydroxy Acids from L-Ascorbic Acid. Useful Components for the Synthesis of Cerebrosides
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Nucleophilic ring opening of chiral epoxy diols, derived from L-ascorbic acid, with 2-lithio-1,3-dithianes allowed preparation of long-chain (R)- and (S)-α-hydroxy acids of high optical purity.
- Yamagata, Kazuyuki,Yamagiwa, Yoshiro,Kamikawa, Tadao
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p. 3355 - 3357
(2007/10/02)
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- Chemistry of L-Ascorbic and D-Isoascorbic Acids. An Efficient Synthesis of 2-Deoxypentofuranoses
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L-Ascorbic and D-isoascorbic acids have been converted to methyl 3-O-benzyl-2-deoxypentofuranosides.The synthetic routes are enantiospecific, efficient, and economic and proceed in high yields.
- Vargeese, Chandra,Abushanab, Elie
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p. 4400 - 4403
(2007/10/02)
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- THE CHEMISTRYL OF L-ASCORBIC AND D-ISOASCORBIC ACIDS. 3: EFFICIENT SYNTHESES OF PURE R- AND S-1,2-O-ISOPROPYLIDENE-1,2,4-BUTANETRIOLS
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Both enantiomers of 1,2-O-isopropylidene-1,2,4-butanetriol were prepared by two different and simple methods starting from readily available L-ascorbic and D-isoascorbic acids.
- Saibaba, Rasha,Sarma, Mallela S. P.,Abushanab, Elie
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p. 3077 - 3086
(2007/10/02)
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