- Design and Synthesis of Piperazine Sulfonamide Cores Leading to Highly Potent HIV-1 Protease Inhibitors
-
Using the HIV-1 protease binding mode of MK-8718 and PL-100 as inspiration, a novel aspartate binding bicyclic piperazine sulfonamide core was designed and synthesized. The resulting HIV-1 protease inhibitor containing this core showed an 60-fold increase in enzyme binding affinity and a 10-fold increase in antiviral activity relative to MK-8718.
- Bungard, Christopher J.,Williams, Peter D.,Schulz, Jurgen,Wiscount, Catherine M.,Holloway, M. Katharine,Loughran, H. Marie,Manikowski, Jesse J.,Su, Hua-Poo,Bennett, David J.,Chang, Lehua,Chu, Xin-Jie,Crespo, Alejandro,Dwyer, Michael P.,Keertikar, Kartik,Morriello, Gregori J.,Stamford, Andrew W.,Waddell, Sherman T.,Zhong, Bin,Hu, Bin,Ji, Tao,Diamond, Tracy L.,Bahnck-Teets, Carolyn,Carroll, Steven S.,Fay, John F.,Min, Xu,Morris, William,Ballard, Jeanine E.,Miller, Michael D.,McCauley, John A.
-
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Read Online
- γ-Difluorolysine as a19F NMR probe for histone lysine methyltransferases and acetyltransferases
-
Histone lysine methylation and acetylation are important posttranslational modifications that regulate gene expression in humans. Due to the interplay of these two modifications, new chemical methods to study lysine posttranslational modifications are highly desired. Here, we report the use of γ-difluorolysine as a lysine mimic and19F NMR probe for examinations of histone methylation and acetylation.
- Hintzen, Jordi C. J.,Jian, Jie,Luo, Yan,Mecinovi?, Jasmin,Porzberg, Miriam R. B.,Proietti, Giordano,White, Paul B.
-
supporting information
p. 6788 - 6791
(2021/07/13)
-
- Method for preparing high-purity (R)-4-formyl-2,2-dimethyl-3-oxazoline tert-butyl carboxylate
-
The invention discloses a method for preparing high-purity (R)-4-formyl-2,2-dimethyl-3-oxazoline tert-butyl carboxylate. The method comprises the following steps: carrying out a reaction on D-serine and thionyl chloride in methanol to obtain a compound 2; carrying out a reaction on the compound 2 and Boc anhydride under triethylamine to obtain a compound 3; carrying out a reaction on the compound3 and 2,2-dimethoxypropane under the action of boron trifluoride diethyl ether to obtain a compound 4; and reducing the compound 4 and DIBAL-H are at a temperature of -60 DEG C to -80 DEG C to obtaina crude product, carrying out a reaction on the crude product and sodium sulfite to form salt, and purifying to obtain the high-purity (R)-4-formyl-2,2-dimethyl-3-oxazoline tert-butyl carboxylate. According to the invention, the salt forming is performed by using the properties of sodium sulfite and an aldehyde group, so that the purity of the salified product can reach 98%, the industrial standard is met, and the production operation is well facilitated.
- -
-
Paragraph 0061; 0074-0076
(2020/03/09)
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- PYRROLE COMPOUNDS
-
Provided herein are compounds of Formula (I), or pharmaceutically acceptable salts thereof, pharmaceutical compositions that include a compound described herein (including pharmaceutically acceptable salts of a compound described herein) and methods of synthesizing the same. Also provided herein are methods of treating diseases and/or conditions with a compound of Formula (I), or a pharmaceutically acceptable salt thereof.
- -
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Paragraph 0123
(2020/10/19)
-
- STABLE N-((1R,2R)-1-(2,3-DIHYDROBENZO[B][1,4]DIOXIN-6-YL)-1-HYDROXY-3-(PYRROLIDIN-1-YL)PROPAN-2-YL) OCTANAMIDE (2R,3R)-2,3-DIHYDROXYSUCCINATE PREMIX AND PROCESS FOR PREPARATION THEREOF
-
The present invention related to stable N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6-yl)- 1-hydroxy-3- (pyrrolidin-1-yl)propan-2-yl) octanamide (2R,3R)- 2,3-dihydroxysuccinate premix of formula (Ia) and its process for preparation thereof. The present invention also related to process for the preparation of N-((1R, 2R)-1-(2,3-dihydrobenzo[b][1,4] dioxin-6- yl)-1-hydroxy-3- (pyrrolidin-1-yl) propan-2-yl) octanamide of formula (I) and pharmaceutically acceptable salts.
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Page/Page column 28
(2019/05/15)
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- Methods and intermediates for synthesizing SK1-I
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The invention provides methods for synthesizing the compound (2R,3S,4E)-N-methyl-5-(4′-pentylphenyl)-2-aminopent-4-ene-1,3-diol, also known as SK1-I, and intermediate compounds used in its synthesis.
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Page/Page column 4
(2019/08/20)
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- PRODRUGS OF GLUTAMINE ANALOGS
-
Prodrugs of glutamine analogs, such as prodrugs of acivicin, are disclosed.
- -
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Paragraph 0201
(2018/08/26)
-
- Solution-phase automated synthesis of an α-amino aldehyde as a versatile intermediate
-
A solution-phase automated synthesis of the versatile synthetic intermediate, Garner's aldehyde, was demonstrated. tert-Butoxycarbonyl (Boc) protection, acetal formation, and reduction of the ester to the corresponding aldehyde were performed utilizing our originally developed automated synthesizer, ChemKonzert. The developed procedure was also useful for the synthesis of Garner's aldehyde analogues possessing fluorenylmethyloxycarbonyl (Fmoc) or benzyloxycarbonyl (Cbz) protection.
- Masui, Hisashi,Yosugi, Sae,Fuse, Shinichiro,Takahashi, Takashi
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p. 106 - 110
(2017/02/15)
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- Novel Easily Recyclable Bifunctional Phosphonic Acid Carrying Tripeptides for the Stereoselective Michael Addition of Aldehydes with Nitroalkenes
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A novel bifunctional organocatalyst library combining both aminocatalysis and phosphonic acid activation was used for the first time as an efficient tool for the stereoselective Michael addition of aldehydes with several aromatic nitroalkenes with good selectivities up to 95:5 dr and 93:7 er. Due to their high water solubility, the catalysts were easily recyclable and could be reused over several cycles without any significant loss of selectivity.
- Cortes-Clerget, Margery,Gager, Olivier,Monteil, Maelle,Pirat, Jean-Luc,Migianu-Griffoni, Evelyne,Deschamp, Julia,Lecouvey, Marc
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supporting information
p. 34 - 40
(2016/01/25)
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- ISOINDOLINE COMPOSITIONS AND METHODS FOR TREATING NEURODEGENERATIVE DISEASE
-
Isoindoline sigma-2 receptor antagonist compounds, pharmaceutical compositions comprising such compounds, and methods for inhibiting Abeta- associated synapse loss or synaptic dysfunction in neuronal cells, modulating an Abeta-associated membrane trafficking change in neuronal cells, and treating cognitive decline associated with Abeta pathology are provided.
- -
-
Paragraph 0481; 0485
(2015/09/23)
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- Synthesis of a novel series of 2,3,4-trisubstituted oxazolidines designed by isosteric replacement or rigidification of the structure and cytotoxic evaluation
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We have previously reported on a study of the structure-activity relationship in a series of 2,3,4-substituted oxazolidines recently discovered by our group varying the substituent at the ring or stereochemistry of the oxazolidine ring. We discovered the cytotoxic and pro-apoptotic potential of compounds 1 and 2 with good selectivity against cancer cell lines. In the present study we describe the synthesis and cytotoxic evaluation against cancer cell lines (HL60, JURKAT, MDA-MB-231 and LNCaP) of a series of oxazolidines designed by isosteric replacement or rigidification of the oxymethylene spacer of compounds 1 and 2. Alkenes 3 and 4 retained the activity against MDA-MB-231 cells and they were more active on HL60, JURKAT and LNCaP cells. Considering LNCaP cells, E-isomer 4 was at least 7 times and about 3 times more potent than lead 1 and Z-isomer 3, respectively. Compound 4 exerted significant activity against LNCaP with IC50 in the low micromolar range (11 μM) without affecting VERO cells and PBMC proliferation (IC50 > 100 μM) indicating its low toxicity to normal cells.
- Andrade, Saulo F.,Teixeira, Claudia S.,Ramos, Jonas P.,Lopes, Marcela S.,Pdua, Rodrigo M.,Oliveira, Mnica C.,Souza-Fagundes, Elaine M.,Alves, Ricardo J.
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p. 1693 - 1699
(2014/12/11)
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- HETEROBICYCLIC COMPOUNDS AS BETA-LACTAMASE INHIBITORS
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The present invention is directed to compounds which are beta-lactamase inhibitors. The compounds and their pharmaceutically acceptable salts, are useful in combination with beta-lactam antibiotics, or alone, for the treatment of bacterial infections, including infections caused by drug resistant organisms, including multi-drug resistant organisms. The present invention includes compounds according to formula (Ia): or a pharmaceutically acceptable salt thereof, wherein the values of R1, R 2, R 3 and R 4 are described herein.
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Page/Page column 170; 171
(2013/10/22)
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- Ugi four-component reaction of alcohols: Stoichiometric and catalytic oxidation/MCR sequences
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A new, simple, and efficient procedure for the one-pot Ugi four-component reaction of alcohols instead of aldehydes is described. Using a stoichiometric amount of IBX or only 1-2% of sodium 2-iodobenzenesulfonate in the presence of Oxone, a wide range of primary alcohols were oxidized to the aldehyde that were directly engaged in the Ugi four-component reaction to afford α-acetamidoamides in good to excellent yields.
- Drouet, Fleur,Masson, Géraldine,Zhu, Jieping
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supporting information
p. 2854 - 2857
(2013/07/26)
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- A stereodivergent route to four stereoisomeric 3′- acetoxycyclopentenylglycine derivatives
-
A short and efficient synthetic route to four stereoisomeric 3-acetoxycyclopentenylglycine derivatives from l-serine has been developed. The method features a stereoselective conjugate addition and ring-closing metathesis as key steps. Georg Thieme Verlag Stuttgart · New York.
- Kundu, Indranil,Maitra, Ratnava,Jana, Manoranjan,Chattopadhyay, Shital K.
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p. 304 - 310
(2012/03/26)
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- Transformation of d-serine to highly functionalized cyclohexenecarboxylates in study of oseltamivir synthesis
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In an attempted synthesis of oseltamivir, D-serine was used to prepare (R)-Garner aldehyde, which reacted with vinylzinc reagent to give an alcohol product predominating in the (1′R,4S)-isomer. After the alcohol was protected as p-methoxybenzyl ether, the N,O-acetal was hydrolyzed and oxidized to an aldehyde, which underwent Reformatsky-type reaction with ethyl α-(bromomethyl)acrylate by promotion of indium to give an addition product readily for ring-closure metathesis to afford 3-alkoxy-4-amido-5-hydroxy-1- cyclohexenecarboxylates. After activation of the 5-hydroxy group as methanesulfonate, an attempted substitution reaction with sodium azide gave unexpectedly a cyclic carbamate via an intramolecular nucleophilic attack of the 4-tert-butoxycarbamate group.
- Lai, Joshua,Fang, Jim-Min
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p. 426 - 435
(2012/08/07)
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- Enantioselective synthesis of Garner's aldehyde by asymmetric hydroformylation
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Both enantiomers of Garner's aldehyde (3) are prepared from the same alkene 4 by catalytic asymmetric hydroformylation.
- Clemens, Alexander J. L.,Burke, Steven D.
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experimental part
p. 2983 - 2985
(2012/06/01)
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- 4,4-Difluorinated analogues of l-arginine and NG-hydroxy-l-arginine as mechanistic probes for nitric oxide synthase
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4,4-Difluoro-l-arginine and 4,4-difluoro-NG-hydroxy-l-arginine were synthesized and shown to be substrates for the inducible isoform of nitric oxide synthase (iNOS). Binding of both fluorinated analogues to the NOS active site was also investigated using a spectral binding assay employing a heme domain construct of the inducible NOS isoform (iNOSheme). 4,4-Difluoro-NG-hydroxy-arginine was found to bind at the NOS active site in a unique manner consistent with a model involving ligation of the FeIII heme center by the oxygen atom of the NG-hydroxy moiety.
- Martin, Nathaniel I.,Woodward, Joshua J.,Winter, Michael B.,Marletta, Michael A.
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supporting information; experimental part
p. 1758 - 1762
(2009/11/30)
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- SPHINGOSINE COMPOUND, METHOD FOR PRODUCING THE SAME, AND SPHINGOMYELINASE INHIBITOR
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An object of the invention is to provide a novel sphingosine compound with an inhibitory activity against sphingomyelinase, and a method for producing the sphingosine compound. The novel sphingosine compound or a salt thereof according to the invention is represented by Formula (1): wherein one of R1 and R2 is hydrogen, and the other is a group represented by Formula (G): wherein n is 0 or 1; and R3 is hydrogen, C1-23 alkyl, C3-8 cycloalkyl, C2-6 alkenyl, C1-6 alkoxy, C3-8 cycloalkyloxy, phenyl, or furil.
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Page/Page column 11
(2009/12/27)
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- The discovery of odanacatib (MK-0822), a selective inhibitor of cathepsin K
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Odanacatib is a potent, selective, and neutral cathepsin K inhibitor which was developed to address the metabolic liabilities of the Cat K inhibitor L-873724. Substituting P1 and modifying the P2 side chain led to a metabolically robust inhibitor with a long half-life in preclinical species. Odanacatib was more selective in whole cell assays than the published Cat K inhibitors balicatib and relacatib. Evaluation in dermal fibroblast culture showed minimal intracellular collagen accumulation relative to less selective Cat K inhibitors.
- Gauthier, Jacques Yves,Chauret, Nathalie,Cromlish, Wanda,Desmarais, Sylvie,Duong, Le T.,Falgueyret, Jean-Pierre,Kimmel, Donald B.,Lamontagne, Sonia,Leger, Serge,LeRiche, Tammy,Li, Chun Sing,Masse, Frederic,McKay, Daniel J.,Nicoll-Griffith, Deborah A.,Oballa, Renata M.,Palmer, James T.,Percival, M. David,Riendeau, Denis,Robichaud, Joel,Rodan, Gideon A.,Rodan, Sevgi B.,Seto, Carmai,Therien, Michel,Truong, Vouy-Linh,Venuti, Michael C.,Wesolowski, Gregg,Young, Robert N.,Zamboni, Robert,Black, W. Cameron
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p. 923 - 928
(2008/12/22)
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- 3-(2-Acylamino-1-Hydroxyethyl)-Morpholine Derivatives and Their Use as Bace Inhibitors
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The present invention provides BACE inhibitors of Formula (I); methods for their use and preparation, and intermediates useful for their preparation.
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Page/Page column 58
(2008/06/13)
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- Synthesis of fluorescent lactosylceramide stereoisomers
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The intracellular distribution of synthetic glycosphingolipids (GSLs) bearing a fluorophore can be monitored in living cells by fluorescence microscopy. We reported previously that variation in the length of the long-chain base and in the structure of the carbohydrate-containing polar head group of (2S,3R) (or d-erythro-)-β-lactosylceramide (LacCer) did not alter the mechanism of endocytic uptake from the plasma membrane of various mammalian cell types [Singh, R.D., Puri, V., Valiyaveettil, J.T., Marks, D.L., Bittman, R., Pagano, R.E., 2003. Selective caveolin-1-dependent endocytosis of glycosphingolipids. Mol. Biol. Cell 14, 3254-3265]. To extend our examination of the molecular features in LacCer that are responsible for its uptake by the caveolar-requiring endocytic pathway, we have synthesized the three unnatural stereoisomers [(2R,3R)-, (2S,3S)-, and (2R,3S)] of dipyrromethene difluoride (BODIPY)-LacCer. These analogues will be used to probe the role of stereochemistry in the long-chain base of LacCer in the mechanism of endocytic uptake.
- Liu, Yidong,Bittman, Robert
-
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- β-isocupreidine-catalyzed Baylis-Hillman reaction of chiral N-Boc-α-amino aldehydes
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β-Isocupreidine (β-ICD)-catalyzed Baylis-Hillman reaction of chiral N-Boc-α-amino aldehydes and 1,1,1,3,3,3-hexafluoroisopropyl acrylate (HFIPA) takes place without racemization and exhibits the match-mismatch relationship between the substrate and the catalyst. In the case of acyclic amino aldehydes, α,-substrates show excellent syn selectivity and high reactivity in contrast to L-substrates. On the other hand, in the case of cyclic amino aldehydes, D-substrates rather than L-substrates show excellent anti selectivity and high reactivity.
- Nakano, Ayako,Takahashi, Keisuke,Ishihara, Jun,Hatakeyama, Susumi
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p. 5357 - 5360
(2007/10/03)
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- Facile synthesis of (s)-5,5-difluoronorleucine and its incorporation in biologically active peptides as an methionine mimetic
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Both Boc and Fmoc protected 5,5-difluoronorleucines (F2Nle) were easily prepared from commercially available amino acid derivatives. F2Nle can be viewed as a mimic of methionine in which the sulfur atom is replaced by the CF2 moiety. Two analogues of methionine-containing biologically active peptides (fMLP and Met-enkephalin) were prepared. The validity of CF2-substituted methionine analogues was confirmed in their biological assay.
- Osada, Satoshi,Ishimaru, Takako,Kawasaki, Hiroshi,Kodama, Hiroaki
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p. 421 - 431
(2007/10/03)
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- 8-AZAPROSTAGLANDIN DERIVATIVES AND MEDICINAL USES THEREOF
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The pharmaceutical composition comprising the compound of the invention having 8-azaprostaglandin skeleton represented by formula (I) (wherein, all the symbols have the same meanings as that of the specification.) a salt thereof, a solvate thereof or a cyclodextrin clathrate thereof, or a prodrug thereof and them as active ingredient have EP4 agonistic action and thus are considered useful for the prevention and/or treatment of immunological diseases, asthma, neuronal cell death, arthritis, lung failure, pulmonary fibrosis, pulmonary emphysema, bronchitis, chronic obstructive pulmonary disease, liver damage, acute hepatitis, nephritis, renal insufficiency, hypertension, myocardial ischemia, systemic inflammatory response syndrome, sepsis, hemophagous syndrome, macrophage activation syndrome, Still''s disease, Kawasaki disease, burn, systemic granulomatosis, ulcerative colitis, Crohn''s disease, hypercytokinemia at dialysis, multiple organ failure, shock and glaucoma, etc. Furthermore, the compounds also have an action of accelerating bone formation, so it is expected to be useful for the prevention and/or treatment of diseases associated with loss in bone mass, for example, primary osteoporosis, secondary osteoporosis, bone metastasis of cancer, hypercalcemia, Paget''s disease, bone loss, osteonecrosis, bone formation after bone operation, alternative treatment for bone grafting.
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Page/Page column 57-58
(2010/02/14)
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- A solid-phase approach to DDB derivatives
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Since the discovery of 2,2′-dimethoxycarbonyl-4,4-dimethoxy-5,6, 5′,6′-biomethylenedioxy-biphenyl (DDB) as a potent anti-HBV agent, we have studied the structure-activity relationships of 4,4′-dimethoxy-5, 6,5′,6′-dimethenedioxy-2-alkyloxycarbonyl-2′-(4-substituted benzyl piperazin-1-yl)carbonyl-biphenyl as anti-HBV agents. Therefore, it is rational to extend this study to the 3,3′-disustituted-4,4′- dimethoxy-5,6,5′,6′-dimethenedioxy-2-alkyloxycarbonyl-2′- Serine derivatives. Thus, in an attempt to develop an efficient method for the preparation of a large number of DDB derivatives, the reaction between a DDB acid chloride and serine derivatives on solid support was studied. The structure of resulted compounds was confirmed by LC-MS and 1H NMR analysis. Compounds 2a, 2d, 2f, 2j showed in vitro anti-HBV activity without significant toxicity up to 100 μM.
- Qi, Xiuxiang,Wang, Xiaolai,Wang, Limin,Wang, Qiang,Cheng, Senxiang,Suo, Jishuan,Chang, Junbiao
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p. 805 - 810
(2007/10/03)
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- Total synthesis of TMC-95A and -B via a new reaction leading to Z-enamides. Some preliminary findings as to SAR
-
A full account of the total syntheses of proteasome inhibitors TMC-95A and -B is provided. A key feature of the syntheses involved installation of a cis-propenylamide moiety by a thermal rearrangement of an α-silylallyl amide. The scope and mechanism of the enamide-forming reaction are discussed. Also provided are some preliminary results from SAR studies. It was found that simplified analogues can retain the full potency of proteasome inhibition.
- Lin, Songnian,Yang, Zhi-Qiang,Kwok, Benjamin H. B.,Koldobskiy, Michael,Crews, Craig M.,Danishefsky, Samuel J.
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p. 6347 - 6355
(2007/10/03)
-
- Novel aliphatic compounds, process for their preparation and their usage
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The present invention provides an aliphatic compound represented by the following formula (I) or pharmacologically acceptable salts thereof: where n denotes an integer of 1 to 11, and 1 denotes an integer of 1 to 16, the aliphatic compound being an optical isomer of the (2R,3S,2′S) configuration when the 8-position thereof is a double bond, or an optical isomer of the (2S,3R,2′RS) configuration when the 8-position is a single bond; methods for producing the compound or pharmacologically acceptable salts thereof; and uses of the compound in the treatment of cardiovascular diseases (e.g. arteriosclerosis, cardiac diseases), cancer, rheumatism, diabetic retinopathy, and respiratory diseases.
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Page/Page column 12
(2010/02/05)
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- ANTIMICROBIAL QUINOLONES, THEIR COMPOSITIONS AND USES
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Compounds of the following formula (I) are effective antimicrobial agents.
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Page 100; 110-111
(2010/02/06)
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- Recyclable 2nd generation ionic liquids as green solvents for the oxidation of alcohols with hypervalent iodine reagents
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Alcohols undergo smooth oxidation with iodoxybenzoic acid (IBX) or with Dess-Martin-Periodinane (DMP) in hydrophilic [bmim]BF4 and hydrophobic [bmim]PF6 ionic liquids at room temperature under mild conditions to afford the corresponding carbonyl compounds in excellent yields with high selectivity. IBX and DMP promoted oxidations are faster in ionic liquids when compared to conventional solvents such as DMSO, DMF, EtOAc and H2O. The recovery of the byproduct iodosobenzoic acid (IBA) is especially simple in ionic liquids. The recovered ionic liquids can be recycled in subsequent reactions with consistent activity.
- Yadav,Reddy,Basak,Venkat Narsaiah
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p. 2131 - 2135
(2007/10/03)
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- Synthesis of trans-(3S)-Amino-(4R)-alkyl- and -(4S)-Aryl-piperidines via Ring-Closing Metathesis Reaction
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(Matrix Presented) trans-(3S)-Amino piperidines bearing various alkyl and aryl substituents at the C-4 position were synthesized via a ring-closing metathesis reaction. The absolute stereochemistry was controlled using a protected D-serine as a starting material. Stereoselective hydrogenation of allylamines provided trans-(3S)-amino-(4R)-alkyl- and -(4S)-aryl-piperidines. This procedure presents the first method for the asymmetric synthesis of 4-substituted 3-amino piperidines.
- Hu, X. Eric,Kim, Nick K.,Ledoussal, Benoit
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p. 4499 - 4502
(2007/10/03)
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- Synthesis of the functionalized macrocyclic core of proteasome inhibitors TMC-95A and B
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An ordered assembly of four building blocks (2-5) forms the basis of the synthesis of 1, which contains the core structure of TMC-95A and B - two potent proteasome inhibitore (see scheme; TIPS = triisopropylsilyl, Cbz = benzoxycarbonyl, Boc = tert-Boc = tert-butoxycarbonyl).
- Lin, Songnian,Danishefsky, Samuel J.
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p. 1967 - 1970
(2007/10/03)
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- A simplified route to the (R)-Garner aldehyde and (S)-vinyl glycinol
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An improved procedure for the conversion of D-serine into tert-butyl (R)-4-formyl-2,2-dimethyloxazolidine-3-carboxylate [the (R)-Garner aldehyde] is described which can be carried out in four operationally simple steps in 88% overall yield. Elaboration of this aldehyde to vinyl glycinol is also described.
- Campbell, Andrew D.,Raynham, Tony M.,Taylor, Richard J. K.
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p. 1707 - 1709
(2007/10/03)
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- Efficient conversion of (S)-methionine into (R)-garner aldehyde
-
An efficient method has been developed for the conversion of L-methionine into N,O-protected D-serinal (Garner aldehyde) in good overall yield.
- Ravi Kumar, Jalluri S.,Datta, Apurba
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p. 6779 - 6780
(2007/10/03)
-
- Convenient procedures for the synthesis of N-BOC-D-serinal acetonide from L-serine
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Two straightforward synthetic routes for the preparation of enantiomerically pure N-BOC-D-serinal acetonide (enantiomer of Garner's aldehyde) starting from naturally occurring L-serine are described.
- Avenoza,Cativiela,Corzana,Peregrina,Zurbano
-
p. 1146 - 1150
(2007/10/03)
-
- Grignard reactions to chiral oxazolidine aldehydes
-
Modest to high levels of asymmetric induction are observed with Grignard additions to Garner type aldehydes. The resultant secondary alcohols are important precursors of chiral building blocks for asymmetric synthesis and we have demonstrated that they can be readily converted into their respective γ-hydroxy-β-amino alcohols and β-hydroxyamino acids. Additionally, aryloxy ethers, important components of many natural products, can be obtained from these precursors.
- Williams, Lorenzo,Zhang, Zhongda,Shao, Feng,Carroll, Patrick J.,Joullie, Madeleine M.
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p. 11673 - 11694
(2007/10/03)
-
- Acyclic analogs of kainoids: Their syntheses and depolarizing activities
-
Four stereoisomers of the β-benzylglutamic acids were synthesized by the Michael addition of benzylphenylsulfide to protected (4S)- and (4R)-4-amino-2-penten-5-olide and to protected (2S)- and (2R)-3-dehydro-2-hydroxymethyl-5-pyrrolidone. The β-methallyl- and β-isobutylglutamic acids were also synthesized in a similar manner. The depolarizing activities of these synthesized compounds were observed.
- Hashimoto, Miwa,Hashimoto, Kimiko,Shirahama, Haruhisa
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p. 1931 - 1942
(2007/10/03)
-
- Asymmetric allylboration of 2-N,3-O-isopropylidene-N-Boc-L-serinal: Diastereoselective synthesis of the calicheamicin γ1(I) amino sugar
-
Syntheses of the calicheamicin amino sugar 6 and its erythro diastereomer 7 have been completed by a sequence involving the asymmetric allylboration of N-Boc-serinal acetonide L-8 with the tartrate ester modified allylboronates (R,R)-9 and (S,S)-9, respectively. The reaction of (R,R)-9 and L-8 in toluene provides 14 with 89:11 selectivity, whereas the reaction of (S,S)-9 with L-8 in Et2O provides the diastereomer 15 with 90:10 selectivity. It is shown that the relatively modest diastereoselectivity of these double asymmetric reactions is compromised by the low enantiomeric purity of 8 (86-87% ee), and data are provided indicating that these reactions should be highly diastereoselective (≥95:5 in each case) if performed with enantiomerically pure aldehyde. The two diastereomeric homoallylic alcohols, 14 and 15, are easily elaborated into the targeted amino sugars 6 and 7 via the acetamide-substituted pyranosides 22 and 26. Methyl pyranosides 22a and 22e were shown to adopt preferentially the unexpected conformations B and D, with axial acetamide substituents, in nonpolar solvents, while the expected conformations A and C were strongly favored in d6-DMSO because of hydrogen bonding interactions with the solvent. The syntheses of 6 and 7 reported herein are expected to facilitate the design and synthesis of analogs of the calicheamicin aryl tetrasaccharide 3, which should prove useful in further analysis and applications of oligosaccharides as DNA binders.
- Roush,Hunt
-
p. 798 - 806
(2007/10/02)
-
- GUANIDINO COMPOUNDS AS REGULATORS OF NITRIC OXIDE SYNTHASE
-
Compounds of the formula:useful as regulators of nitric oxide synthase that indirectly modulate cyclic guanosine monophosphate (cGMP), pharmaceutical compositions thereof, for treating disorders of vascular smooth muscles, macrophages, neurons, platelets, bronchial smooth muscles, optic muscles and gastrointestinal smooth muscles, sickle cell anemia and diabetes.
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-
-
- Guanidino compounds as regulators of nitric oxide synthase
-
Compounds of the formula: STR1 useful as regulators of nitric oxide synthase that indirectly modulate cyclic guanosine monophosphate (cGMP), pharmaceutical compositions thereof, for treating disorders of vascular smooth muscles, macrophages, neurons, platelets, bronchial smooth muscles, optic muscles and gastrointestinal smooth muscles, sickle cell anemia and diabetes.
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-
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- SYNTHESIS OF ACYCLIC ANALOGUES OF KAINOIDS AND NEUROEXCITATORY ACTIVITY
-
Four configurational isomers of 3-benzylglutamic acid, acyclic analogues of kainoids were synthesized to examine their structure-activity relationship.
- Yanagida, Miwa,Hashimoto, Kimiko,Ishida, Michiko,Shinozaki, Haruhiko,Shirahama, Haruhisa
-
p. 3799 - 3802
(2007/10/02)
-
- A Straightforward Synthesis of Allyl Amines from α-Amino Acids without Racemization
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An extremely simple and practical synthesis of allyl amine derivatives from α-amino acids has been developed involving aldehyde olefination pathway with AlMe3-Zn-CH2I2 reagent which has proven to be crucial for preservation of stereochemical integrity.
- Moriwake, Toshio,Hamano, Shin-ichi,Saito, Seiki,Torii, Sigeru
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p. 2085 - 2088
(2007/10/02)
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- The Synthesis and Configurational Stability of Differentially Protected β-Hydroxy-β-amino Aldehydes
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Syntheses of 1,1-dimethylethyl (S)-4-formyl-2,2-dimethyl-3-oxazolidinecarboxylate (5) and 1,1-dimethylethyl (4S-trans)-4-formyl-2,2,5-trimethyl-3-oxazolidinecarboxylate (6) from commercially available serine and threonine derivatives are described.The method involves selective reduction of the corresponding oxazolidine esters 3 and 4 using diisobutylaluminum hydride at low temperature.These differentially protected β-hydroxy-α-amino aldehydes are also shown to be produced in 93-95 percent enantiomeric excess (via NMR and HPLC analysis of the Mosher esterderivatives 8 and epi-8)-thus making them useful as chiral, nonracemic synthons for asymmetric synthesis.
- Garner, Philip,Park, Jung Min
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p. 2361 - 2364
(2007/10/02)
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