- Synthesis of new C3 symmetric amino acid- and aminoalcohol-containing chiral stationary phases and application to HPLC enantioseparations
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We recently reported a new C3-symmetric (R)-phenylglycinol N-1,3,5-benzenetricarboxylic acid-derived chiral high-performance liquid chromatography (HPLC) stationary phase (CSP 1) that demonstrated better results as compared to a previously described N-3,5-dintrobenzoyl (DNB) (R)-phenylglycinol-derived CSP. Over a decade ago, (S)-leucinol, (R)-phenylglycine, and (S)-leucine derivatives were used as the starting materials of 3,5-DNB-based Pirkle-type CSPs for chiral separation. In this study, three new C3-symmetric CSPs (CSP 2, 3, and 4) were prepared by combining the ideas and results mentioned above. Here we describe the synthetic procedures and applications of the new C3-symmetric CSPs (CSP 2–CSP 4).
- Yu, Jeongjae,Armstrong, Daniel W.,Ryoo, Jae Jeong
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- syn-Diastereoselective glycolate aldol addition reactions of an N(3)-(p-methoxyphenoxy)acetyloxazolidine-2-thione
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An N3-(p-methoxyphenoxy)acetyloxazolidine-2-thione has been synthesized and employed in glycolate asymmetric aldol addition reactions with aromatic and aliphatic aldehydes. It was determined that the titanium tetrachloride medicated aldol reaction afforded diastereoselectivities that ranged from 75:25 to 94:6 when the reaction was conducted at ?78?°C. The absolute stereochemistry of the aldol adducts was determined by1H NMR spectroscopy and X-ray crystallography. The1H NMR spectra of the aldol adducts contained a signal (the α-proton of the glycolate position of the aldol side chain) that was highly deshielded due to conformational restriction about the N(3)-(p-methoxyphenoxy)acetyl side chain and the oxazolidine-2-thione auxiliary.
- Haynes, Craig S.,Goodman, Cassie A.,Bruce, Juandah,Genin, Sarah C.,Austermuehle, Brad J.,Leong, Victor L.,Leise, Austin R.,Larson, Robert,Hamaker, Christopher G.,Hitchcock, Shawn R.
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- Convenient approach to chiral 4-monosubstituted 1,3-oxazolidine-2-thiones
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Chiral 4-monosubstituted 1,3-oxazolidine-2-thiones are regarded as one of the modified version of Evans auxiliaries in asymmetric aldol condensation, which can generate two adjacent chiral carbon centers in one time They have advantages over Evans auxiliaries in some aspects, however, their application is highly limited by their preparation approaches as toxic or flammable chemicals are involved. Here, a mild and applicable procedure for preparing the chiral oxazolidine-2-thione auxiliaries has been developed in this article. Potassium ethylxanthate and the corresponding chiral amino alcohols as the starting material in absolute ethanol are mixed and the mixture are heated under reflux for 1 h in open air to provide 1,3-oxazolidine-2-thiones chiral auxiliaries in moderate to excellent yields.
- Lu, Zheng,Yang, Yong-Qing,Li, Jiu-Hui,Wei, Jun-Nan,Wang, Yi-Zhu
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supporting information
p. 2215 - 2219
(2017/10/31)
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- Thiocarbonyl Surrogate via Combination of Sulfur and Chloroform for Thiocarbamide and Oxazolidinethione Construction
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An efficient and practical thiocarbonyl surrogate via combination of sulfur and chloroform has been developed. A variety of thiocarbamides and oxazolidinethiones have been established, including chiral thiourea catalysts and chiral oxazolidinethione auxiliaries with high selectivity. Meanwhile, pesticides Diafenthiuron (an acaricide), ANTU (a rodenticide), and Chloromethiuron (an insecticide) were practically synthesized through this method in gram scale. Dicholorocarbene, as the key intermediate, was further confirmed via a carbene-trapping control experiment.
- Tan, Wei,Wei, Jianpeng,Jiang, Xuefeng
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supporting information
p. 2166 - 2169
(2017/04/27)
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- Synthesis, X-ray analysis, and biological activities of novel oxazolidinethiones
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Oxazolidinethione compounds were synthesized starting from racemic and enantiopure β-amino alcohols. The molecular structure of oxazolidinethione 6a was elucidated by single-crystal x-ray crystallography. Oxazolidinethione compounds screened for antimicro
- Saygili, Nezire,?zalp, Meral,Yildirim, Leyla Tatar
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p. 1264 - 1269
(2015/04/27)
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- Potent and Selective Inhibitors of Histone Deacetylase-3 Containing Chiral Oxazoline Capping Groups and a N-(2-Aminophenyl)-benzamide Binding Unit
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A novel series of potent chiral inhibitors of histone deacetylase (HDAC) is described that contains an oxazoline capping group and a N-(2-aminophenyl)-benzamide unit. Among several new inhibitors of this type exhibiting Class I selectivity and potent inhibition of HDAC3-NCoR2, in vitro assays for the inhibition of HDAC1, HDAC2, and HDAC3-NCoR2 by N-(2-aminophenyl)-benzamide 15k gave respective IC50 values of 80, 110, and 6 nM. Weak inhibition of all other HDAC isoforms (HDAC4, 5, 6, 7, and 9: IC50 > 100000 nM; HDAC8: IC50 = 25000 nM; HDAC10: IC50 > 4000 nM; HDAC11: IC50 > 2000 nM) confirmed the Class I selectivity of 15k. 2-Aminoimidazolinyl, 2-thioimidazolinyl, and 2-aminooxazolinyl units were shown to be effective replacements for the pyrimidine ring present in many other 2-(aminophenyl)-benzamides previously reported, but the 2-aminooxazolinyl unit was the most potent in inhibiting HDAC3-NCoR2. Many of the new HDAC inhibitors showed higher solubilities and lower binding to human serum albumin than that of Mocetinostat. Increases in histone H3K9 acetylation in the human cell lines U937 and PC-3 was observed for all three oxazolinyl inhibitors evaluated; those HDAC inhibitors also lowered cyclin E expression in U937 cells but not in PC-3 cells, indicating underlying differences in the mechanisms of action of the inhibitors on those two cell lines.
- Marson, Charles M.,Matthews, Christopher J.,Atkinson, Stephen J.,Lamadema, Nermina,Thomas, N. Shaun B.
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p. 6803 - 6818
(2015/09/22)
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- ANTI-CANCER POLYKETIDE COMPOUNDS
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Provided herein, inter alia, are anticancer polyketides. The uses of the polyketides described herein include treatment of cancer, for example, through regulation of the spliceosome and detection of spliceosome inhibition.
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Paragraph 0157
(2013/10/21)
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- Total synthesis of γ-trifluoromethylated analogs of goniothalamin and their derivatives
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An efficient method for the construction of chiral γ- trifluoromethylated α,β-unsaturated δ-lactone, a widely existing pharmacophore, has been developed and successfully applied for synthesis of γ-trifluoromethylated goniothalamins. The key steps included Evans-Aldol reaction of chiral titanium enolate of α-CF3 imide, Wittig olefination and lactonization. The transformation of γ-trifluoromethylated α,β-unsaturated δ-lactone to a series of trifluoromethylated styryllactones was also investigated.
- Chen, Jun-Ling,You, Zheng-Wei,Qing, Feng-Ling
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p. 143 - 150
(2013/10/01)
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- Structure of FD-895 revealed through total synthesis
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The total synthesis of FD-895 was completed through a strategy that featured the use of a tandem esterification ring-closing metathesis (RCM) process to construct the 12-membered macrolide and a modified Stille coupling to append the side chain. These stu
- Villa, Reymundo,Mandel, Alexander L.,Jones, Brian D.,La Clair, James J.,Burkart, Michael D.
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supporting information
p. 5396 - 5399
(2013/01/15)
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- Intramolecular sulfur transfer in N-enoyl oxazolidine-2-thiones promoted by Bronsted acids. Practical asymmetric synthesis of β-mercapto carboxylic acids and mechanistic insights
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The ability of Bronsted acids alone to efficiently promote the sulfur transfer process in N-enoyl oxazolidine-2-thiones to give β-mercapto carbonyl derivatives is demonstrated. The reactions proceed with essentially perfect diastereocontrol for a range of alkyl-substituted N-enoyl oxazolidine-2-thiones (d.r. regularly above 98:2) and high selectivity for most aryl-substituted counterparts (d.r. typically above 92:8). Importantly, the reaction works remarkably well in β,β-disubstituted N-enoyl oxazolidine-2-thiones as well, giving rise to quaternary C-S stereocenters in selectivities usually above 95:5. The relative efficiency of a range of acids (trifluoroacetic, difluoroacetic, acetic, triflic) is assessed showing TFA and TfOH as the most efficient and acetic acid as a totally inefficient reaction promoter. The new procedure complements the Lewis acid promoted reaction previously described by our group in two aspects: First, stereodivergent results are obtained for the Lewis acid or Bronsted acid promoted reactions of β,β-disubstituted enoyl compounds. Second, while the Bronsted acid promoted reactions are stereospecific, providing a good correlation between the substrate E/Z configuration and products stereochemistry, the reactions mediated by Lewis acids (BF3/OEt2) provide invariant d.r. values regardless of the E/Z composition of the starting olefin. The synthetic value of the method is illustrated by (a) removal of the oxazolidinone moiety from the rearranged products under reducing conditions (NaBH4, H 2O-THF) which yields β-mercapto alcohols and (b) treatment with Sm(OTf)3 in MeOH which affords the corresponding β-mercapto carboxylic esters, both categories of compounds being isolated in up to 97% ee. Remarkably, the method constitutes the first general approach to highly enantioenriched building blocks bearing a quaternary C-S stereocenter. On the other hand, spectroscopic and inhibition experiments are carried out that demonstrate the participation of protons also in the Lewis acid promoted reactions. Finally, the computational studies carried out at the B3LYP/6-31G* level give support for an activation of the substrate enoyl by complexation with two molecules of either the Bronsted or Lewis acid and serve to explain the stereochemical outcome of the reactions.
- Palomo, Claudio,Oiarbide, Mikel,Lopez, Rosa,Gonzalez, Pedro B.,Gomez-Bengoa, Enrique,Saa, Jose M.,Linden, Anthony
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p. 15236 - 15247
(2007/10/03)
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- A facile access to chiral 4-isopropyl-, 4-benzyl-, and 4-phenyloxazolidine-2-thione
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A highly practical procedure for preparing the chiral oxazolidine-2-thione auxiliaries using carbon disulfide and the corresponding chiral amino alcohols as the starting materials in the presence of potassium carbonate and hydrogen peroxide is presented.
- Wu, Yikang,Yang, Yong-Qing,Hu, Qi
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p. 3990 - 3992
(2007/10/03)
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- Asymmetric aldol additions: Use of titanium tetrachloride and (-)-sparteine for the soft enolization of N-acyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones
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Asymmetric aldol additions using chlorotitanium enolates of N-acyloxazolidinone, oxazolidinethione, and thiazolidinethione propionates proceed with high diastereoselectivity for the Evans or non-Evans syn product depending on the nature and amount of the base used. With 1 equiv of titanium tetrachloride and 2 equiv of (-)-sparteine as the base or 1 equiv of (-)-sparteine and 1 equiv of N-methyl-2-pyrrolidinone, selectivities of 97:3 to >99:1 were obtained for the Evans syn aldol products using N-propionyl oxazolidinones, oxazolidinethiones, and thiazolidinethiones. The non-Evans syn aldol adducts are available with the oxazolidinethione and thiazolidinethiones by altering the Lewis acid/amine base ratios. The change in facial selectivity in the aldol additions is proposed to be a result of switching of mechanistic pathways between chelated and nonchelated transition states. The auxiliaries can be reductively removed or cleaved by nucleophilic acyl substitution. Iterative aldol sequences with high diastereoselectivity can also be accomplished.
- Crimmins,King,Tabet,Chaudhary
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p. 894 - 902
(2007/10/03)
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- 2-Chloro-1,3-dimethylimidazolinium chloride. 2. Its application to the construction of heterocycles through dehydration reactions
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2-Chloro-1,3-dimethylimidazolinium chloride (DMC) (1) can act as a powerful dehydrating equivalent to DCC (2) under nearly neutral conditions. Its application to the construction of heterocycles through dehydration reactions is described.
- Isobe, Toshio,Ishikawa, Tsutomu
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p. 6989 - 6992
(2007/10/03)
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- Synthesis and pyrolytic behaviour of thiazolidin-2-one 1,1-dioxides
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Four examples of the chiral thiazolidin-2-one 1,1-dioxides 5 have been prepared by reaction of the appropriate amino alcohols 11 with CS2 in aqueous sodium hydroxide to give the thiazolidine-2-thiones 12, followed by oxidation with KMnO4 under phase-transfer conditions in the presence of benzoic acid, either directly or via the thiazolidin-2-ones 13. Upon flash vacuum pyrolysis (FVP) at 650°C, 5a-c decompose mainly by loss of SO2 to give an alkene and benzyl isocyanate together with other products from fragmentation of the N-benzyl group. A significant minor pathway involves net loss of CO2 and water to give the 2-phenyl-4,5-dihydrothiazoles 21 together with their aromatisation products 22 and 23. A mechanism for this new heterocyclic transformation is proposed involving initial expansion to a cyclic carbamic-sulnnic anhydride (2,1,4-oxathiazin-3-one 1-oxide). The fully assigned 13C NMR spectra are presented for 5, 12 and 13 and the 33S NMR spectrum has been obtained for 5c.
- Aitken, R. Alan,Armstrong, David P.,Galt, Ronald H. B.,Mesher, Shaun T. E.
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p. 2139 - 2145
(2007/10/03)
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- Preparation of Oxazolidin-2-ones by Oxidation of Oxazolidine-2-thiones. A Proton Magnetic Resonance Structural Study
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The preparation of a series of oxazolidine-2-thiones, both homochiral and racemic, as well as their oxidation to oxazolidin-2-ones is reported.X-Ray and pmr studies have showed that the stereochemical integrity of the starting aminoalcohol is maintained.
- Moreno-Manas, Marcial,Padros, Imma
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p. 1235 - 1240
(2007/10/02)
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- Synthesis of optically active α-phenylselenyl carbonyl derivatives
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Homochiral silyl enol ethers derived from N-acyl oxazolidinones can be phenyselenylated in high diastereoselectivity and good yield with phenylselenyl chloride. Removal of the chiral auxiliary is accompanied by some epimerisation, leading to isolation of
- Holmes,Nadin,O'Hanlon,Pearson
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p. 1289 - 1302
(2007/10/02)
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