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Journal of the American Pharmaceutical... Oct 1946
Topics: Amino Alcohols; Ethanolamines
PubMed: 21002915
DOI: 10.1002/jps.3030351006 -
Organic Letters Nov 2019Asymmetric synthesis of γ-amino alcohols from unprotected allylic alcohols by a copper-catalyzed hydroamination strategy has been developed. Using easily accessible...
Asymmetric synthesis of γ-amino alcohols from unprotected allylic alcohols by a copper-catalyzed hydroamination strategy has been developed. Using easily accessible starting materials, a range of chiral 1,3-amino alcohols were prepared with excellent regio- and enantioselectivity. Further, this protocol provided an efficient one-step method for the enantioselective synthesis of γ-amino alcohols in an intermolecular manner.
Topics: Amination; Amino Alcohols; Catalysis; Chemistry Techniques, Synthetic; Copper
PubMed: 31625750
DOI: 10.1021/acs.orglett.9b03356 -
Amino Acids 1999Lipidic alpha-amino acids (LAAs) are a class of compounds combining structural features of amino acids with those of fatty acids. They are non-natural alpha-amino acids... (Review)
Review
Lipidic alpha-amino acids (LAAs) are a class of compounds combining structural features of amino acids with those of fatty acids. They are non-natural alpha-amino acids with saturated or unsaturated long aliphatic side chains. Synthetic approaches to optically active LAAs and lipidic 2-amino alcohols (LAALs) are summarized in this review. A general approach to enantioselective synthesis of saturated LAAs is based on the oxidative cleavage of 3-amino-1,2-diols obtained by the regioselective opening of enantiomerically enriched long chain 2,3-epoxy alcohols. Unsaturated LAAs are prepared in their enantiomeric forms by Wittig reaction via methyl (S)-2-di-tert-butoxycarbonylamino-5-oxo-pentanoate. This key intermediate aldehyde is obtained by selective reduction of dimethyl N,N-di-Boc glutamate with DIBAL. (R) or (S) LAALs may be prepared starting from D-mannitol or L-serine. LAAs are converted into LAALs by chemoselective reduction of their fluorides using sodium borohydride with retention of optical purity. Replacement of the hydroxyl group of LAALs by the azido group, followed by selective reduction leads to unsaturated optically active lipidic 1,2-diamines.
Topics: Amino Alcohols; Fatty Acids; Stereoisomerism
PubMed: 10399016
DOI: 10.1007/BF01388172 -
Organic Letters Dec 2020We report a DNA-compatible photoredox decarboxylative coupling of α-amino acids with carbonyl compounds to access DNA-encoded sp-rich 1,2-amino alcohols. The reaction...
We report a DNA-compatible photoredox decarboxylative coupling of α-amino acids with carbonyl compounds to access DNA-encoded sp-rich 1,2-amino alcohols. The reaction proceeds efficiently for a wide range of DNA-conjugated aldehydes and ketones and provides the desired 1,2-amino alcohols with conversions generally >50%. Additional utility of the developed protocol is demonstrated by one-pot cyclization of DNA-conjugated 1,2-amino alcohols into oxazolidiones and morpholinones. Lastly, qPCR and sequencing data analysis indicates no significant DNA damage upon photoredox decarboxylative coupling.
Topics: Amino Alcohols; Catalysis; Cyclization; DNA; Ketones; Molecular Structure; Oxidation-Reduction
PubMed: 33170713
DOI: 10.1021/acs.orglett.0c03461 -
Angewandte Chemie (International Ed. in... Mar 2014The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has...
The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2-azaadamantane N-oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol-selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen-containing compounds.
Topics: Amino Alcohols; Catalysis; Molecular Structure; Organic Chemicals; Oxidation-Reduction
PubMed: 24554411
DOI: 10.1002/anie.201309634 -
Biotechnology Letters Aug 2020To screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic β-amino alcohols.
OBJECTIVES
To screening of bacteria with cyclic amino alcohol deamination activity for enantioselective synthesis of chiral cyclic β-amino alcohols.
RESULTS
A new strain named Arthrobacter sp. TYUT010-15 with the (R)-selective deamination activity of cyclic β-amino alcohol has been isolated from nature via a high throughput solid-phase screening method. The reaction conditions of TYUT010-15 were optimized. Using the resting cell of TYUT010-15 as the catalyst, kinetic resolution of trans-2-aminocyclopentanol, trans-2-aminocyclohexanol and cis-1-amino-2-indanol was carried out to afford (1S, 2S)-trans-2-aminocyclopentanol, (1S, 2S)-trans-2-aminocyclohexanol and (1R, 2S)-cis-1-amino-2-indanol in > 99% ee and 49.6-50% conversion. Four aromatic β-amino alcohols and two amines were also resolved, (S)-β-amino alcohols and (R)-amines were obtained in > 99% ee. Preparation experiment was conducted with 200 mM (23.2 g L) racemic trans-2-aminocyclohexanol, yielding the desired (1S, 2S)-trans-2-aminocyclohexanol in 40% isolated yield, > 99% ee and 5.8 g L d space time yields.
CONCLUSIONS
This study provides a high throughput solid-phase method for screening of bacteria with cyclic amino alcohol deamination activity and a first example for practical preparation of chiral cyclic β-amino alcohol by Arthrobacter sp. TYUT010-15.
Topics: Amines; Amino Alcohols; Arthrobacter; Bacteria; Colorimetry; Deamination; High-Throughput Screening Assays; Kinetics; Stereoisomerism; Substrate Specificity
PubMed: 32219689
DOI: 10.1007/s10529-020-02869-2 -
The Journal of Organic Chemistry Sep 2018Chiral 1,2-amino alcohols are privileged scaffolds with important applications as drug candidates and chiral ligands. Although various methods for the preparation of...
Chiral 1,2-amino alcohols are privileged scaffolds with important applications as drug candidates and chiral ligands. Although various methods for the preparation of this structural motif have been reported, these methods are limited because of the use of precious metals and ligands. Here, we report a practical and high yielding synthesis of chiral 1,2-amino alcohols using arylglyoxals and pseudoephedrine auxiliary. This reaction is catalyzed by a Brønsted acid and provides morpholinone products in high yields and selectivities. The morpholine ring was converted into 1,2-amino alcohols in a two-step protocol.
Topics: Amino Alcohols; Chemistry Techniques, Synthetic; Glyoxal; Morpholines; Stereoisomerism
PubMed: 30039699
DOI: 10.1021/acs.joc.8b01516 -
Nature Apr 2016The chirality, or 'handedness', of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and...
The chirality, or 'handedness', of a biologically active molecule can alter its physiological properties. Thus it is routine procedure in the drug discovery and development process to prepare and fully characterize all possible stereoisomers of a drug candidate for biological evaluation. Despite many advances in asymmetric synthesis, developing general and practical strategies for obtaining all possible stereoisomers of an organic compound that has multiple contiguous stereocentres remains a challenge. Here, we report a stereodivergent copper-based approach for the expeditious construction of amino alcohols with high levels of chemo-, regio-, diastereo- and enantioselectivity. Specifically, we synthesized these amino-alcohol products using sequential, copper-hydride-catalysed hydrosilylation and hydroamination of readily available enals and enones. This strategy provides a route to all possible stereoisomers of the amino-alcohol products, which contain up to three contiguous stereocentres. We leveraged catalyst control and stereospecificity simultaneously to attain exceptional control of the product stereochemistry. Beyond the immediate utility of this protocol, our strategy could inspire the development of methods that provide complete sets of stereoisomers for other valuable synthetic targets.
Topics: Amination; Amino Alcohols; Catalysis; Chemistry Techniques, Synthetic; Copper; Molecular Structure; Stereoisomerism
PubMed: 27018656
DOI: 10.1038/nature17191 -
Chemical Communications (Cambridge,... Oct 2015The γ-amino alcohol structural motif is often encountered in drugs and natural products. We developed two complementary catalytic diastereoselective methods for the...
The γ-amino alcohol structural motif is often encountered in drugs and natural products. We developed two complementary catalytic diastereoselective methods for the synthesis of N-PMP-protected γ-amino alcohols from the corresponding ketones. The anti-products were obtained through Ir-catalyzed asymmetric transfer hydrogenation, the syn-products via Rh-catalyzed asymmetric hydrogenation.
Topics: Amino Alcohols; Catalysis; Hydrogenation; Stereoisomerism
PubMed: 26273707
DOI: 10.1039/c5cc04445f -
Journal of Mass Spectrometry : JMS Jan 2014The enantiomeric differentiation of a series of chiral β-amino alcohols (A) is attempted, for the first time, by applying the kinetic method using L-proline,...
The enantiomeric differentiation of a series of chiral β-amino alcohols (A) is attempted, for the first time, by applying the kinetic method using L-proline, L-tryptophan, 4-iodo-L-phenylalanine or 3, 5-diiodo-L-tyrosine as the chiral references (Ref) and Cu(2+) or Ni(2+) ion (M) as the central metal ion. The trimeric diastereomeric adduct ions, [M+(Ref)2+A-H](+), formed under electrospray ionization conditions, are subjected for collision-induced dissociation (CID) experiments. The products ions, formed by the loss of either a reference or an analyte, detected in the CID spectra are evaluated for the enantiomeric differentiation. All the references showed enantiomeric differentiation and the R(chiral) values are better for the aromatic alcohols than for aliphatic alcohols. Notably, the R(chiral) values of the aliphatic amino alcohols enhanced when Ni(2+) is used as the central metal ion. The experimental results are well supported by computational studies carried out on the diastereomeric dimeric complexes. The computational data of amino alcohols is correlated with that of amino acids to understand the structural interaction of amino alcohols with reference molecule and central metal ion and their role on the stabilization of the dimeric complexes. Application of flow injection MS/MS method is also demonstrated for the enantiomeric differentiation of the amino alcohols.
Topics: Amino Alcohols; Models, Molecular; Spectrometry, Mass, Electrospray Ionization; Stereoisomerism
PubMed: 24446270
DOI: 10.1002/jms.3312