- Synthesis and evaluation of chirally defined side chain variants of 7-chloro-4-aminoquinoline to overcome drug resistance in malaria chemotherapy
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A novel 4-aminoquinoline derivative [(S)-7-chloro-N-(4-methyl-1-(4-methyl-piperazin-1-yl)pentan-2-yl)-quinolin-4-amine triphosphate] exhibiting curative activity against chloroquine-resistant malaria parasites has been identified for preclinical development as a blood schizonticidal agent. The lead molecule selected after detailed structure-activity relationship (SAR) studies has good solid-state properties and promising activity against in vitro and in vivo experimental malaria models. The in vitro absorption, distribution, metabolism, and excretion (ADME) parameters indicate a favorable drug-like profile.
- Dola, Vasantha Rao,Soni, Awakash,Agarwal, Pooja,Ahmad, Hafsa,Raju, Kanumuri Siva Rama,Rashid, Mamunur,Wahajuddin, Muhammad,Srivastava, Kumkum,Haq,Dwivedi,Puri,Katti
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- Synthesis of enantiopure free and N-benzyloxycarbonyl-protected 3-substituted homotaurines from naturally occurring amino acids
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Enantiopure N-benzyloxycarbonyl-protected and free 3-substituted homotaurines were synthesized from naturally occurring amino acids via N-benzyloxycarbonyl protection, Arndt-Eistert homologation, reduction, esterification with thioacetic acid, and oxidation with performic acid. The current method is a convenient, practical, and salt-free method for the synthesis of enantiopure 3-substituted homotaurine with moderate to good yields.
- Zheng, Yongpeng,Xu, Jiaxi
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p. 5197 - 5206
(2014/12/10)
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- Synthesis of enantiopure free and N-benzyloxycarbonyl-protected 3-substituted homotaurines from naturally occurring amino acids
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Enantiopure N-benzyloxycarbonyl-protected and free 3-substituted homotaurines were synthesized from naturally occurring amino acids via N-benzyloxycarbonyl protection, Arndt-Eistert homologation, reduction, esterification with thioacetic acid, and oxidation with performic acid. The current method is a convenient, practical, and salt-free method for the synthesis of enantiopure 3-substituted homotaurine with moderate to good yields.
- Zheng, Yongpeng,Xu, Jiaxi
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p. 5197 - 5206
(2014/07/08)
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- Acylation of alkyl halides and amino aldehydes with a phosphane oxide-based d1-synthon
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Alkyl iodides and α-amino aldehydes can be homologated to the corresponding methyl esters and β-amino methyl esters, including β-amino-α-hydroxy methyl esters, using lithiated (dimethoxymethyl) diphenylphosphane oxide. The primary α,α-(dimethoxy) diphenylphosphane oxides obtained by this Horner-Wittig type process collapse to give the target esters under proton-catalyzed conditions in the presence of water. Detailed and carefully conducted mechanistic studies revealed that the diphenylphosphane oxide group is activated by protonation, and acts as the initial leaving group in this process. In the cases of adducts derived from the reaction of the phosphane oxide-stabilized anion with α-amino aldehydes, homologation to the β-amino- and β-amino-α-hydroxy methyl esters can be achieved by KOtBu-mediated elimination to the intermediate O,O-ketene acetals. These may either be allowed to react with water under acidic conditions to yield the β-amino methyl esters, or may be treated under the Sharpless asymmetric dihydroxylation conditions to directly furnish the β-amino-α-hydroxy methyl esters. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004.
- Bruenjes, Marco,Kujat, Christof,Monenschein, Holger,Kirschning, Andreas
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p. 1149 - 1160
(2007/10/03)
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- A convenient preparation of (2SR,3S)-3-amino-2-hydroxy-4-phenylbutanoic acid; an important peptide bond isostere
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We present an efficient synthesis of N-Z-(2SR,3S)-3-amino-2-hydroxy-4- phenylbutanoic acids by hydroxylation of an enolate derived from methyl (3S)N-Z-3-amino-4-phenylbutanoate with oxodiperoxymolybdenum (pyridine) (hexamethyl phosphoric triamide) complex
- May, Barnaby C.H.,Abell, Andrew D.
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p. 2515 - 2525
(2007/10/03)
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- Peptidyl β-homo-aspartals: Specific inhibitors of interleukin-1β converting enzyme and its homologues (caspases)
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Inhibition of interleukin-1β convening enzyme (ICE), apopain, papain, thrombin and trypsin with substrate like peptidyl L- and D-α-aldehydes and their L-β-homo-aldehyde analogues was investigated. The L-β-homo-aspartals appear to be specific inhibitors fo
- Bajusz, Sandor,Fauszt, Iren,Nemeth, Klara,Barabas, Eva,Juhasz, Attila,Patthy, Miklos
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p. 1477 - 1482
(2007/10/03)
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- Synthesis of enantiopure N-and C-protected homo-β-amino acids by direct homologation of α-amino acids
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Enantiopure N-and/or C-protected homo-β-amino acids are prepared readily and in good yields from N-protected α-amino acids with the same side chain, via reduction of the carboxyl function and conversion of the resulting N-protected β-amino alcohol into the corresponding β-amino iodide and then β-amino cyanide. The key step of this strategy is represented by the synthesis of the enantiopure N-protected β-amino iodides 2 and 3 that are smoothly obtained from the parent amino alcohols 1 by polymer bound triarylphosphine-I2 complex in anhydrous dichloromethane.
- Caputo, Romualdo,Cassano, Ersilia,Longobardo, Luigi,Palumbo, Giovanni
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p. 12337 - 12350
(2007/10/02)
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- On the Preparation of β-Amino Acids from α-Amino Acids Using the Arndt-Eistert Reaction: Scope, Limitations and Stereoselectivity. Application to Carbohydrate Peptidation. Stereoselective α-Alkylations of Some β-Amino Acids
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The Arndt-Eistert homologation of α-amino acids was studied to determine the stereoselectivity in this reaction by chromatographic up-to-date analytical methods.While carbamate-protected phenylglycine was transformed to the corresponding β-amino acid methyl ester with a stereoselectivity of only 9:1, all other tested amino acid derivatives (Ala, Phe, Ser, Orn, tert-Leu and perhydro-azepine-2-carboxylic acid, suitably protected) were homologated with full retention of configuration (products 9-17).The intermediate diazo ketones 1-8 were purified and characterized by their NMR spectra.When nucleophiles derived from partially protected sugars were present during decomposition of the diazo ketones (derived from amino acids or dipeptides), a strong dependence of the yield (products 21-24) on the degree of steric hindrance of the nucleophilic OH group was observed.Two of the β-amino acids obtained from the homologation reaction were transformed to α-substituted (25-27, 31, 32) and α,α-disubstituted β-amino acid derivatives (28, 29) with excellent selctivities (in most cases, a single diastereoisomer was obtained). - Key Words: β-Amino acids, α-branched/Glycopeptides
- Podlech, Joachim,Seebach, Dieter
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p. 1217 - 1228
(2007/10/02)
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- Synthesis of gastrin antagonists, analogues of the C-terminal tetrapeptide of gastrin, by introduction of a β-homo residue
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A series of analogues of Boc-Trp-Leu-Asp-Phe-NH2, a potent gastrin agonist, were synthesized by introducing a β-homo residue in the sequence. These compounds were tested in vivo on acid secretion, in the anesthetized rat, and for their ability
- Rodriguez,Fulcrand,Laur,Aumelas,Bali,Martinez
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p. 522 - 528
(2007/10/02)
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- AMINO THIOL DIPEPTIDES
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Amino thiol substituted dipeptides of the formula STR1 are disclosed. These compounds are useful as hypotensive agents due to their angiotensin converting enzyme inhibition activity and depending upon the definition of X may also be useful as analgesics due to their enkephalinase inhibition activity.
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