Amino Alcohol Derivatives Research Articles

ChemInform Abstract: Diastereodivergent Synthesis of Amino Alcohol Derivatives from N-Acyl- N,O-Acetals. S×2-Type Displacement with Organocopper-Boron Trifluoride Reagents.

ChemInform Abstract: Diastereodivergent Synthesis of Amino Alcohol Derivatives from N-Acyl- N,O-Acetals. S×2-Type Displacement with Organocopper-Boron Trifluoride Reagents.

2-Hydroxy-N,N′-diisopropylpropane-1,3-diaminium dichloride

In the crystal structure of the title amino alcohol derivative, C9H24N2O2+·2Cl−, the cations and anions are linked by inter­molecular O—H⋯Cl and N—H⋯Cl hydrogen bonds into a three-dimensional network.

ChemInform Abstract: A New Chiral Stationary Phase for Gas Chromatography by Use of a Chiral Thiacalix[4]arene Derivative.

A new chiral stationary phase for capillary gas chromatography based on a chirally modified p-tert-butylthiacalix[4]arene with (S)-1-phenylethylamine was prepared to show good separations of enantiomeric amino acid, amine and alcohol derivatives, while the corresponding p-tert-butylcalix[4]arene counterpart did not differentiate the enantiomers.

ChemInform Abstract: Fluorine-Containing Optically Active Allylic Alcohols: Preparation and Claisen Rearrangement as a New Entry to Highly Functionalized Fluorinated Amino Alcohol Derivatives.

The reaction of Garner aldehyde 1 with 2-bromo-3,3,3-trifluoropropene in the presence of Zn–Ag couple gave the fluorine-containing, optically active allylic alcohol 2 in 65% yield with a diastereomeric excess greater than 98%. The treatment of Garner aldehyde 1 with CF3CFBr2 (3a) and CF3CCl3 (3b) in the presence of zinc powder and catalytic AlCl3 highly diastereoselectively afforded 4a and 4b, respectively, in moderate yield. The orthoester Claisen rearrangement of 4a, b and 2 provided a new way to highly functionalized amino alcohol derivatives 6a–f containing a limited number of fluorine atoms.

Metabolism-guided design of short-acting calcium-sensing receptor antagonists.

As part of a strategy to deliver short-acting calcium-sensing receptor (CaSR) antagonists, the metabolically labile thiomethyl functionality was incorporated into the zwitterionic amino alcohol derivative 3 with the hope of increasing human clearance through oxidative metabolism, while delivering a pharmacologically inactive sulfoxide metabolite. The effort led to the identification of thioanisoles 22 and 23 as potent and orally active CaSR antagonists with a rapid onset of action and short pharmacokinetic half-lives, which led to a rapid and transient stimulation of parathyroid hormone in a dose-dependent fashion following oral administration to rats. On the basis of the balance between target pharmacology, safety, and human disposition profiles, 22 and 23 were advanced as clinical candidates for the treatment of osteoporosis.

Exploration of amino alcohol derivatives as novel, potent, and highly selective sphingosine-1-phosphate receptor subtype-1 agonists

In pursuit of a potent and highly selective sphingosine-1-phosphate receptor agonists with an improved in vivo conversion of the precursor to the active phospho-drug, we have utilized previously reported phenylamide and phenylimidazole scaffolds to identify a selectivity enhancing moiety (SEM) and selectivity enhancing orientation (SEO) within both pharmacophores. SEM and SEO have allowed for over 100 to 500-fold improvement in selectivity for S1P receptor subtype 1 over subtype 3. Utility of SEM and SEO and further SAR study allowed for discovery of a potent and selective preclinical candidate PPI-4955 (21b) with an excellent in vivo potency and dose responsiveness and markedly improved overall in vivo pharmacodynamic properties upon oral administration.

Highly Efficient Asymmetric Synthesis of Vinylic Amino Alcohols by Zn‐Promoted Benzoyloxyallylation of Chiral N‐tert‐Butanesulfinyl Imines: Facile and Rapid Access to (−)‐Cytoxazone

An efficient and convenient alpha-hydroxyallylation approach for the asymmetric synthesis of a variety of beta-amino-alpha-vinyl alcohols has been successfully developed. A wide range of vinylic amino alcohol derivatives could be obtained in very good yields and with excellent diastereomeric ratios of up to 99:1 in favor of anti isomers by highly diastereoselective Zn-promoted benzoyloxyallylation of chiral N-tert-butanesulfinyl imines with 3-bromopropenyl benzoate at room temperature. In particular, excellent enantioinduction of the two new stereogenic centers was observed, with up to 98% ee. The method provides a new route for the direct alpha-hydroxyallylation of imines in a highly stereoselective manner. Moreover, the synthetic value of the method has also been demonstrated by the most concise and straightforward synthesis of (-)-cytoxazone yet reported.

Diastereoselective Synthesis of γ-Amino-δ-hydroxy-α,α-difluorophosphonates: A Vehicle for Structure−activity Relationship Studies on SMA-7, a Potent Sphingomyelinase Inhibitor

A highly diastereoselective synthesis of 2-amino alcohol derivatives bearing a difluoromethylphosphonothioate group at the 3-position was achieved through LiAlH(O-t-Bu)(3)-mediated reduction of the corresponding alpha-amino ketones. The phosphonothioate moiety of the product was readily converted into the corresponding phosphonate by oxidation with m-CPBA, followed by aqueous workup. The developed methods should be useful for SAR studies of SMA-7, a potent inhibitor of SMases.

Formal Highly Enantioselective Organocatalytic Addition of Fluoromethyl Anion to α,β‐Unsaturated Aldehydes

Symmetric fluoromethylation made easy: a highly enantioselective fluoromethyl addition to ?,?-unsaturated aldehydes is described (see scheme). The synthesis of chiral fluorinated blocks, including ?-fluoro-?-aminoalcohol derivatives is disclosed.

Chiral Lewis base promoted trichlorosilane reduction of ketimines. An enantioselective organocatalytic synthesis of chiral amines

The reduction of the carbon–nitrogen double bond is an important transformation. Here we report our studies on a family of chiral organic catalysts able to promote the stereoselective reduction of ketimines with trichlorosilane. The very cheap, metal-free catalysts were easily prepared in one step from commercially available products, namely a chiral aminoalcohol and picolinic acid derivatives. The catalyst structure was extensively modified in a study that allowed to identify an extremely active species, able to promote the reduction on a large variety of substrates with high efficiency (up to 95% ee). A three component methodology has been also developed, where the enantiomerically enriched amine was isolated after performing the reaction by mixing a ketone and an amine in the presence of trichlorosilane and the catalyst. Its synthetic potentiality was demonstrated by employing the present metal-free catalytic procedure in the preparation of ( S)-metolachlor, a potent and widely used herbicide.

A convenient synthesis of chiral amino acid derived 3,4-dihydro-2 H-benzo[ b][1,4]thiazines and antibiotic levofloxacin

A series of 3,4-dihydro- 2H-benzo[ b][1,4]thiazine derivatives 8a– g were synthesized via- a copper-catalyzed intramolecular N-aryl amination reaction on substituted 2-(2-bromophenylthio)-ethanamines which were synthesized by the nucleophilic substitution reaction of 2-bromobenzenethiol with Boc-protected amino alcohol derivatives. This strategy provides a short and an efficient entry to ( S)-3-methyl-1,4-benzoxazine 12, an advanced synthetic intermediate for the synthesis of levofloxacin.

Anti- Trichomonas vaginalis activity of synthetic lipophilic diamine and amino alcohol derivatives

Taking in account the increased prevalence of metronidazole-resistant infections, alternative drugs are necessary for the treatment of trichomonosis. We report in this work the preparation and the in vitro anti-trichomonads activity of two diamines 1 and 2, and three different lipophilic amino alcohol derivatives 3, 4 and 5. These compounds were tested for in vitro activity against two isolates of Trichomonas vaginalis and displayed inhibition of the parasite growth. Five concentrations of each compound were tested. The butanediamine derivative 1, at a final concentration of 5.85 μM, presented a cytotoxic effect against 47% of T. vaginalis trophozoites. Furthermore, the cytotoxicity of 1 did not present statistically significant difference when compared to metronidazole in the same range of concentration (0.1–1.5 μg/mL).

Intermolecular Cycloaddition of N-Boranonitrone with Alkenes

Ethyl glyoxylate O-tert-butyldimethylsilyloxime (8), on treatment with 2.2 equiv of BF3 x OEt2, generated N-boranonitrone E, which underwent intermolecular cycloaddition with alkenes 18 to afford isoxazolidines 19 in moderate to high yields. The cycloaddition of N-boranonitrone E with most of the alkenes gave 3,5-trans isoxazolidines as the major isomers via a concerted mechanism. However, in the case of 1-methylated cyclic alkenes (18j and 18l), the cycloaddition surprisingly furnished the 3,3a-cis-cycloadducts (19j and 19l) as major isomers. A possible explanation is that the reaction of 1-methylated cyclic alkenes proceeds mainly via a stepwise mechanism. This reaction of terminal alkenes is very useful for synthesis of 1,3-anti aminoalcohol derivatives by reductive cleavage of an N-O bond.

Comparative QSTR study of a series of alcohol derivatives against Tetrahymena pyriformis

AbstractThe quantitative structure toxicity relationship (QSTR) models of 89 alcohol derivatives have been made with the help of quantum chemical and topological descriptors. The molecular modeling and geometry optimization have been carried out with CAChe pro software. The calculations of quantum chemical descriptors have been done by MOPAC 2002 of topological descriptors by Dragon software. The study indicates that quantum chemical descriptors better predict the toxicity of amino, halogenated and unsaturated alcohol derivatives, while toxicity of acetylenic, diols, and saturated alcohol derivatives are better predicted by topological descriptors as indicated by correlation coefficient and cross validation coefficient (rCVˆ2) values of the QSTR models. The predicted toxicity (PT) values obtained by these QSTR models are close to observed toxicity. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009

Tin-Free Radical Addition of Acyloxymethyl to Imines

Acyloxymethyl radicals were generated from the corresponding iodomethyl esters and successfully underwent addition to the CN bond of N-Ts, N-PMP, and N-Dpp imines by the action of dimethylzinc or triethylborane. Ethyl acetate, toluene, and benzene as well as dichloromethane were suitable solvents. The utility of acyloxymethyl radicals as a hydroxymethyl anion equivalent was highlighted by the facile hydrolysis of the acyloxy moiety of the adducts to give the corresponding amino alcohol derivatives in good to high yield.

ChemInform Abstract: Synthesis of N‐Aryl Derivatives of Vicinal Aminoalcohols

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of N-aryl derivatives of vicinal aminoalcohols

Synthesis was performed of substituted 2-propanols based on glycidyl phenyl and glycidyl allyl ethers, Also some acetic acid esters were prepared.

Modulation of Vα19 NKT cell immune responses by α‐mannosyl ceramide derivatives consisting of a series of modified sphingosines

We have demonstrated that analogues of alpha-mannosyl ceramide (alpha-ManCer) consisting of a series of immunosuppressive 2-aminoalcohol derivatives in place of sphingosine promote a greater immune response from mouse invariant Valpha19-Jalpha26 (AV19-AJ33) TCR-bearing NKT (Valpha19 NKT) cells than alpha-ManCer itself. To further characterize the immune responses of Valpha19 NKT cells to the alpha-ManCer analogues, cytokine production by the cells was examined in detail. We found that certain alpha-ManCer derivatives individually induced either Th1- or Th2-dominant cytokine production in culture. The Th1- or Th2-biased immune responses of Valpha19 NKT cells were dependent on MHC class I-like MR1, since they were induced by coculture with the MR1 transfectants previously loaded with the glycolipids and were inhibited in the presence of anti-MR1 antiserum. Presumably, the recognition of the alpha-mannosyl residue of the alpha-ManCer analogues by the invariant TCR is individually modulated, depending on the altered interaction with the groove of the antigen-presenting MR1. Priming of the Valpha19 invariant TCR-transgenic mice in vivo with these glycolipid derivatives resulted in the induction of the Th1- or Th2-biased immune responses. Thus, these alpha-ManCer derivatives are likely to be useful in immunotherapy for either Th1 or Th2 excess autoimmune diseases, modulating the function of Valpha19 NKT cells.

Syntheses of 1,2-Amino Alcohols and Their Applications for Oxazaborolidine Catalyzed Enantioselective Reduction of Aromatic Ketones

Six new chiral 1,2-amino alcohol derivatives have been synthesized starting from (1R,2R)-2-amino-1-phenylpropane-1,3-diol. Asymmetric reduction of aryl ketones with in-situ generated oxazaborolidine from these amino alcohol derivatives and BH3·Me2S afforded secondary alcohols with good yield and moderate to high enantiomeric excess.

Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis

A simple procedure for obtaining and purifying two degradation products of efavirenz (amino alcohol and quinoline derivatives) from drug substance hydrolysis is described. These impurities are known to exhibit very different UV absorbance properties from those of the parent compound, making determination using a quantitation factor (QF) inaccurate. The obtained hydrolysis products were characterized by physicochemical methods to assure identity, purity and strength. Quinoline derivative was of high purity degree (100%) and amino alcohol was 98.74% pure. Both were set as reference standards in chromatographic related compounds test for efavirenz drug substance and tablets analyses.