152830-08-5Relevant academic research and scientific papers
A convenient method for the kinetic resolution of racemic 2-hydroxyalkanoates using diphenylacetic anhydride (DPHAA) and a chiral acyl-transfer catalyst
Nakata, Kenya,Sekiguchi, Akihiro,Shiina, Isamu
experimental part, p. 1610 - 1619 (2012/01/03)
Diphenylacetic anhydride (DPHAA) was found to be a useful reagent for the kinetic resolution of racemic 2-hydroxyalkanoates in the presence of a catalytic amount of (R)-benzotetramisole ((R)-BTM). The combined use of DPHAA and (R)-BTM effectively produced a variety of the optically active 2-hydroxyalkanoates and the corresponding 2-acyloxyalkanoates from racemic 2-hydroxyalkanoates (s-values = 42-177). A fairly broad substrate scope was demonstrated by this novel chiral induction system. We also revealed that the use of only 0.3 equiv of DPHAA is enough to provide the optically active 2-acyloxyalkanoates in good yields and with excellent ee's by the added use of 0.3 equiv of pivalic anhydride for the kinetic resolution of the racemic 2-hydroxyalkanoates. Copyright
METHOD FOR PRODUCING OPTICALLY ACTIVE 2-HYDROXY ESTER AND NOVEL INTERMEDIATE COMPOUND
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Page/Page column 6, (2012/01/13)
Disclosed is a method for producing an optically active 2-hydroxy ester, comprising selectively esterifying one enantiomer of a racemic 2-hydroxy ester in a solvent containing a catalyst such as tetramisole or benzotetramisole, and a carboxylic acid anhydride, or a carboxylic acid anhydride and a carboxylic acid. In particular, in the case where the solvent contains a carboxylic acid anhydride, but does not contain a carboxylic acid, as the carboxylic acid anhydride, a carboxylic acid anhydride containing a tertiary or quaternary carbon atom in the a-position is used. On the other hand, in the case where the solvent contains a carboxylic acid anhydride and a carboxylic acid, as the carboxylic acid, a carboxylic acid containing a tertiary or quaternary carbon atom in the a-position is used.
Kinetic resolution of the racemic 2-hydroxyalkanoates using the enantioselective mixed-anhydride method with pivalic anhydride and a chiral acyl-transfer catalyst
Shiina, Isamu,Nakata, Kenya,Ono, Keisuke,Sugimoto, Masuhiro,Sekiguchi, Akihiro
supporting information; experimental part, p. 167 - 172 (2010/03/26)
A variety of optically active 2-hydroxyalkanoates and the corresponding 2-acyloxyalkanoates are produced by the kinetic resolution of racemic 2-hydroxyalkanoates by using achiral 2,2-diarylacetic acid with hindered carboxylic anhydrides as the coupling reagents. The combined use of diphenylacetic acid, pivalic anhydride, and (+)-(R)-benzotetramisole ((R)-BTM) effectively produces (S)-2-hydroxyalkanoates and (R)-2-acyloxyalkanoates from the racemic 2-hydroxyalkanoates (s-values = 47-202). This protocol directly provides the desired chiral 2-hydroxyalkanoate derivatives from achiral diarylacetic acid and racemic secondary alcohols that do not include the sec-phenethyl alcohol moiety by using the transacylation process to generate the mixed anhydrides from the acid components with bulky carboxylic anhydrides under the influence of the chiral acyl-transfer catalyst. The transition state that provides the desired (R)-2-acyloxyalkanoate from (R)-2-hydroxyalkanoate included in the racemic mixture is disclosed by DFT calculations, and the structural features of the transition form are also discussed.
Synthesis, conformation and PKC isozyme surrogate binding of new lactone analogues of benzolactam-V8s
Nakagawa, Yu,Irie, Kazuhiro,Masuda, Akiko,Ohigashi, Hajime
, p. 2101 - 2115 (2007/10/03)
To investigate the role of the amide hydrogen of benzolactam-V8s (1-3) on protein kinase C (PKC) isozyme binding, new lactone analogues of benzolactam-V8s with hydrophobic side chains at positions 8 and/or 9 (5-8) were synthesized. The PKC binding affinities of 8- and 9-decylbenzolactone-V8 (5,6) were much lower than those of 8- and 9-decylbenzolactam-V8 (2,3), respectively, indicating that the amide hydrogen of benzolactam-V8s plays a critical role in PKC binding. 8-Decylbenzolactam-V8 (2) showed lower binding affinities to all PKC isozymes compared with those of 9-decylbenzolactam-V8 (3). The binding affinities of 8-substituted benzolactones (5,7,8) were also lower than those of 9-decylbenzolactone-V8 (6), but their PKC isozyme selectivity was higher than those of 2, 3 and 6. 8-Decybenzolactone-V8 (5) exhibited the most significant η-C1B selectivity among the four benzolactones (5-8) synthesized in this study.
A compact chemical miniature of a holoenzyme, coenzyme NADH linked dehydrogenase. Design and synthesis of bridged NADH models and their highly enantioselective reduction
Kanomata, Nobuhiro,Nakata, Tadashi
, p. 4563 - 4568 (2007/10/03)
An L-lactate dehydrogenase that requires coenzyme NADH catalyzes the enantioselective reduction of pyruvate to L-lactate in anaerobic glycolysis. As the first homochiral ansa-type NADH models, we designed the bridged NADH models 10a-c having a parapyridinophane structure for strictly mimicking the stereospecificity of hydrogen transfer in the biological asymmetric reduction with NADH. These models were synthesized in several steps from the corresponding bridged nicotinate 5 prepared by our novel pyridine-formation reaction of formyl-substituted (vinylimino)phosphorane 4 with methyl propiolate. The bridged NADH models 10a-c effected excellent biomimetic reduction at various temperatures in the presence of magnesium ion to achieve both the enantioselective and stereospecific reduction of the pyruvate analogues 12u-z into chiral lactate analogues 13u-z with 88-99% ee. The high enantioselectivity was almost completely dependent on the planar chirality of 10a-c but not on the nature of the substituents of their carbamoyl groups. The biomimetic reduction proceeded with retention of the planar chirality, showing that the bridged NADH models are useful for being recycled. An isotope experiment with the deuterated model (±)-10d confirmed the stereospecific hydrogen transfer, which is in good accordance with natural coenzyme characteristics. The model (S)-10c also exhibited good enantioselectivity for the reduction of activated ketones 14k-n into the corresponding chiral alcohols 15k-n with 79-89% ee. The simple bridged NADH model (S)-10c having both a primary carbamoyl group and a shielding bridge feigning an enzyme wall suggests a compact chemical miniature of a holoenzyme, coenzyme NADH linked dehydrogenase, in terms of the unique structure, high enantioselectivity, and recyclability.
Non-peptide Renin Inhibitors Containing 2-(((3-Phenylpropyl)phosphoryl)oxy)alkanoic Acid Moieties as P2-P3 Replacements
Raddatz, Peter,Minck, Klaus-Otto,Rippmann, Friedrich,Schmitges, Claus-Jochen
, p. 486 - 497 (2007/10/02)
A series of novel renin inhibitors containing 2-(((3-phenylpropyl)phosphoryl)oxy)alkanoic acid moieties as P2-P3 surrogates are presented.The P2-P3 mimetics were obtained from (ω-phenylalkyl)phosphinic acids 1a-c and 2-hydroxyalkanoic acid benzyl esters 2a-f by N,N'-dicyclohexylcarbodiimide-mediated coupling and subsequent oxidation with sodium metaperjodate.Ester cleavage of these derivatives and coupling with P1-P'1 transition-state mimetics I-VII provided highly selective compounds with inhibitory potencies in the lower nanomolar range.Small renin inhibitors, such as analogues 8c and 8h with molecular weights of 539 and 537, respectively, could be prepared.These compounds exhibited IC50 values of about 20 nM against human plasma renin.Compound 7i was examined in vivo for its hypotensive effect.In salt-depleted cynomolgus monkeys, 7i inhibited plasma renin activity almost completely and lowered blood pressure after oral adiministration of a dose of 30 mg/kg.
