- Synthesis and absolute configuration of acanthodendrilline, a new cytotoxic bromotyrosine alkaloid from the Thai marine sponge acanthodendrilla sp.
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Acanthodendrilline (1), a new bromotyrosine alkaloid, was isolated from the Thai marine sponge Acanthodendrilla sp. The structure of 1 was fully characterized by spectroscopic analysis, in agreement with the synthesized compound used to resolve the single
- Sirimangkalakitti, Nachanun,Yokoya, Masashi,Chamni, Supakarn,Chanvorachote, Pithi,Plubrukrn, Anuchit,Saito, Naoki,Suwanborirux, Khanit
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p. 258 - 262
(2016/04/05)
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- Design and synthesis of 2-amino-6-(1H,3H-benzo[de]isochromen-6-yl)-1,3,5- triazines as novel Hsp90 inhibitors
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A novel series of 2-amino-1,3,5-triazines bearing a tricyclic moiety as heat shock protein 90 (Hsp90) inhibitors is described. Molecular design was performed using X-ray cocrystal structures of the lead compound CH5015765 and natural Hsp90 inhibitor geldanamycin with Hsp90. We optimized affinity to Hsp90, in vitro cell growth inhibitory activity, water solubility, and liver microsomal stability of inhibitors and identified CH5138303. This compound showed high binding affinity for N-terminal Hsp90α (Kd = 0.52 nM) and strong in vitro cell growth inhibition against human cancer cell lines (HCT116 IC50 = 0.098 μM, NCI-N87 IC50 = 0.066 μM) and also displayed high oral bioavailability in mice (F = 44.0%) and potent antitumor efficacy in a human NCI-N87 gastric cancer xenograft model (tumor growth inhibition = 136%).
- Suda, Atsushi,Kawasaki, Ken-Ichi,Komiyama, Susumu,Isshiki, Yoshiaki,Yoon, Dong-Oh,Kim, Sung-Jin,Na, Young-Jun,Hasegawa, Kiyoshi,Fukami, Takaaki A.,Sato, Shigeo,Miura, Takaaki,Ono, Naomi,Yamazaki, Toshikazu,Saitoh, Ryoichi,Shimma, Nobuo,Shiratori, Yasuhiko,Tsukuda, Takuo
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p. 892 - 905
(2014/01/23)
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- 2-(4-Carbonylphenyl)benzoxazole inhibitors of CETP: Attenuation of hERG binding and improved HDLc-raising efficacy
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The development of 2-phenylbenzoxazoles as inhibitors of cholesteryl ester transfer protein (CETP) is described. Efforts focused on finding suitable replacements for the central piperidine with the aim of reducing hERG binding: a main liability of our benchmark benzoxazole (1a). Replacement of the piperidine with a cyclohexyl group successfully attenuated hERG binding, but was accompanied by reduced in vivo efficacy. The approach of substituting a piperidine moiety with an oxazolidinone also attenuated hERG binding. Further refinement of this latter scaffold via SAR at the pyridine terminus and methyl branching on the oxazolidinone led to compounds 7e and 7f, which raised HDLc by 33 and 27 mg/dl, respectively, in our transgenic mouse PD model and without the hERG liability of previous series.
- Sweis, Ramzi F.,Hunt, Julianne A.,Sinclair, Peter J.,Chen, Ying,Eveland, Suzanne S.,Guo, Qiu,Hyland, Sheryl A.,Milot, Denise P.,Cumiskey, Anne-Marie,Latham, Melanie,Rosa, Raymond,Peterson, Larry,Sparrow, Carl P.,Anderson, Matt S.
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scheme or table
p. 2597 - 2600
(2011/06/20)
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- A facile Ph3P/CO2 mediated, one-pot synthesis of 2-oxazolidinones from 1, 2-azido alcohols via phosphazene and isocyanate intermediates
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A facile, efficient and convenient method has been developed for the one-pot synthesis of 2-oxazolidinones from the corresponding 1, 2-azido alcohols via phosphazene and isocyanate intermediates in presence of Ph 3P/CO2 in toluene.
- Madhusudhan,Reddy, M. Srinivasa,Reddy, Y. Narayana,Vijayalakshmi,Suribabu,Balraju
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experimental part
p. 978 - 984
(2010/10/19)
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- Formation of enantiopure 5-substituted oxazolidinones through enzyme-catalysed kinetic resolution of epoxides
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(Chemical Equation Presented) Halohydrin dehalogenase from Agrobacterium radiobacter catalyzed the enantioselective ring opening of terminal epoxides with cyanate as a nucleophile, yielding 5-substituted oxazolidinones in high yields and with high enantiopurity (69-98% ee). This is the first example of the biocatalytic conversion of a range of epoxides to the corresponding oxazolidinones.
- Elenkov, Maja Majeric,Tang, Lixia,Meetsma, Auke,Hauer, Bernhard,Janssen, Dick B.
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supporting information; experimental part
p. 2417 - 2420
(2009/05/26)
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- CETP INHIBITORS DERIVED FROM BENZOXAZOLE ARYLAMIDES
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Compounds having the structure of Formula I, including pharmaceutically acceptable salts of the compounds, are potent CETP inhibitors, and are useful for raising HDL-cholesterol, reducing LDL-cholesterol, and for treating or preventing atherosclerosis. In formula I, A-B is an arylamide moiety.
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Page/Page column 25-26
(2009/01/23)
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- Stereoselective synthesis of novel (R)- and (S)-5-azidomethyl-2-oxazolidinones from (S)-epichlorohydrin: a key precursor for the oxazolidinone class of antibacterial agents
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A facile synthesis of novel (R)- and (S)-5-azidomethyl-2-oxazolidinones starting from (S)-epichlorohydrin is described. The (R)-azide was utilized for the preparation of Linezolid.
- Madhusudhan,Om Reddy,Rajesh,Ramanatham,Dubey
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p. 3060 - 3062
(2008/09/20)
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- A facile synthesis of 2-((5R)-2-oxo-5-oxazolidinyl)methyl-1H-isoindole-1, 3(2H)-dione
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Synthesis of enantiomerically pure 2-((5A)-2-oxo-5-oxazolidinyl) methyl)-1H-isoindole-1,3(2H)-dione, a key precursor in the preparation of oxazolidinone class of antibacterial agents starting from (S)-epichlorohydrin has been achieved.
- Madhusudhan,Ready, G. Om,Ramanatham,Dubey
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p. 1264 - 1268
(2007/10/03)
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- Electrogenerated chiral 4-methoxy-2-oxazolidinones as diastereoselective amidoalkylation reagents for the synthesis of β-amino alcohol precursors
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A flexible and efficient synthesis of enantiomerically pure 4,5-substituted 2-oxazolidinones - important target molecules as precursors of pharmacologically active 2-oxazolidinones, β-amino alcohols, β-blockers and azasugar derivatives - is described. As starting materials, the enantiopure storage forms of chiral N-acyliminium ions (4RS,5S)-5-chloromethyl-4-methoxy-1,3-oxazolidin-2-one (2) and (4RS,5R)-4-methoxy-5-methyl-1,3-oxazolidin-2-one (3) were used; these are readily available from the chiral pool with the aid of electrochemical transformations. Substitution of the 4-methoxy group in building blocks 2 and 3 with a large variety of organometallic nucleophiles resulted in the trans-diastereoselective formation of enantiopure 4,5-disubstituted 2-oxazolidinones, with a high degree of flexibility in the substituent at the 4-position.
- Schierle-Arndt, Kerstin,Kolter, Doris,Danielmeier, Karsten,Steckhan, Eberhard
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p. 2425 - 2433
(2007/10/03)
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- A three-step synthesis of optically active 5-halomethyl-2-oxazolidinones; asymmetric desymmetrization of prochiral 1,3-dihalo-2-propyl carbamates
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Optically active 5-bromomethyl-2-oxazolidinones (2a and 3a) and 5-chloromethyl-2-oxazolidinones (2b and 3b) were readily prepared from prochiral 1,3-dibromo-2-propanol (7a) and 1,3-dichloro-2-propanol (7b) by a three-step sequence involving formation of carbamates (6a-c) followed by asymmetric desymmetrization (up to 50% de) and debenzylation by anisole-methanesulfonic acid system.
- Sugiyama, Shigeo,Morishita, Kenji,Ishii, Keitaro
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p. 353 - 364
(2007/10/03)
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- Enzymatic ammonolysis of ethyl (±)-4-chloro-3-hydroxybutanoate. Chemoenzymatic syntheses of both enantiomers of pyrrolidin-3-ol and 5- (chloromethyl)-1,3-oxazolidin-2-one
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Lipase B from Candida antarctica efficiently catalysed the kinetic resolution of ethyl (±)-4-chloro-3-hydroxybutanoate through an ammonolysis reaction. Using this methodology, both enantiomers of 4-chloro-3- hydroxybutanamide were prepared and converted into pyrrolidin-3-ol and 5- (chloromethyl)-1,3-oxazolidin-2-one by simple processes consisting of a reduction reaction and a Hofmann rearrangement, respectively.
- Garcia-Urdiales, Eduardo,Rebolledo, Francisca,Gotor, Vicente
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p. 721 - 726
(2007/10/03)
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- Efficient Pathways to (R)- and (S)-5-Hydroxymethyl-2-oxazolidinone and some Derivatives
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2-Oxazolidinones are a very interesting class of compounds due to their various pharmacological effects.Two new syntheses of enantiomerically pure (R)- and (S)-5-hydroxymethyl-2-oxazolidinone have been developed starting with D-mannitol, L-ascorbic acid and (R)- or (S)-malic acid. (R)- and (S)-5-hydroxymethyl-2-oxazolidinone have been used to synthesize some new homochiral 2-oxazolidinone derivatives.
- Danielmeier, Karsten,Steckhan, Eberhard
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p. 1181 - 1190
(2007/10/02)
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