Acyclic Amino Research Articles

ChemInform Abstract: Efficient Organocatalysts Derived from Simple Chiral Acyclic Amino Acids in Asymmetric Catalysis.

AbstractReview: ca. 60 refs.

Corrigendum: Highly Enantioselective Co‐Catalytic Direct Aldol Reactions by Combination of Hydrogen‐Bond Donating and Acyclic Amino Acid Catalysts

Corrigendum: Highly Enantioselective Co‐Catalytic Direct Aldol Reactions by Combination of Hydrogen‐Bond Donating and Acyclic Amino Acid Catalysts

1,2-Dimethoxy-4,5-dimethylene: a new protecting group for acyclic amino acid derivatives prepared by Stevens rearrangement

A new protecting group, 1,2-dimethoxy-4,5-dimethylene, for acyclic amino acid derivatives could be introduced by N,N-dialkylation with 1,2-bis(bromomethyl)-4,5-dimethoxybenzene (1) and removed via amine de-alkylation with acyl chlorides. The method can be used with base-induced [2,3] and [1,2] Stevens rearrangement products.

Efficient organocatalysts derived from simple chiral acyclic amino acids in asymmetric catalysis

Download options Please wait... Article information DOI https://doi.org/10.1039/C1CY00347J Article type Perspective Submitted 30 Aug 2011 Accepted 17 Oct 2011 First published 10 Nov 2011 Download Citation Catal. Sci. Technol., 2012,2, 29-41 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions Efficient organocatalysts derived from simple chiral acyclic amino acids in asymmetric catalysis Z. Chai and G. Zhao, Catal. Sci. Technol., 2012, 2, 29 DOI: 10.1039/C1CY00347J To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page. If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given. If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page. Read more about how to correctly acknowledge RSC content. Social activity Tweet Share Search articles by author Zhuo Chai Gang Zhao

Isoform-selective thiazolo[5,4-b]pyridine S1P1 agonists possessing acyclic amino carboxylate head-groups

Replacement of the azetidine carboxylate of an S1P1 agonist development candidate, AMG 369, with a range of acyclic head-groups led to the identification of a novel, S1P3-sparing S1P1 agonist, (−)-2-amino-4-(3-fluoro-4-(5-(1-phenylcyclopropyl)thiazolo[5,4-b]pyridin-2-yl)phenyl)-2-methylbutanoic acid (8c), which possessed good in vivo efficacy and pharmacokinetic properties. A 0.3mg/kg oral dose of 8c produced a statistically significant reduction in blood lymphocyte counts 24h post-dosing in female Lewis rats.

Highly Enantioselective Co‐Catalytic Direct Aldol Reactions by Combination of Hydrogen‐Bond Donating and Acyclic Amino Acid Catalysts

AbstractHighly enantioselective co‐catalytic direct aldol reactions by a combination of simple hydrophobic acyclic amino acid and hydrogen‐bond donating catalysts are presented. The corresponding aldol products are formed in high yields with high regio‐, diastereo‐ (anti or syn) and enantioselectivity (up to 99.5:0.5 er). The catalyst loadings can be decreased to as little as 2 mol%.

ChemInform Abstract: Bergman Cyclization of Acyclic Amino Acid Derived Enediynes Leads to the Formation of 2,3‐Dihydrobenzo[f]isoindoles.

AbstractHeating of the enediynes (Ia)—(Ic) in the presence of cyclohexadiene renders possible the new access to dihydrobenzoisoindoles via Bergmann cyclization and subsequent intramolecular nucleophilic substitution.

The effects of parent body processes on amino acids in carbonaceous chondrites

Abstract– To investigate the effect of parent body processes on the abundance, distribution, and enantiomeric composition of amino acids in carbonaceous chondrites, the water extracts from nine different powdered CI, CM, and CR carbonaceous chondrites were analyzed for amino acids by ultra performance liquid chromatography-fluorescence detection and time-of-flight mass spectrometry (UPLC-FD/ToF-MS). Four aqueously altered type 1 carbonaceous chondrites including Orgueil (CI1), Meteorite Hills (MET) 01070 (CM1), Scott Glacier (SCO) 06043 (CM1), and Grosvenor Mountains (GRO) 95577 (CR1) were analyzed using this technique for the first time. Analyses of these meteorites revealed low levels of two- to five-carbon acyclic amino alkanoic acids with concentrations ranging from approximately 1 to 2,700 parts-per-billion (ppb). The type 1 carbonaceous chondrites have a distinct distribution of the five-carbon (C5) amino acids with much higher relative abundances of the γ- and δ-amino acids compared to the type 2 and type 3 carbonaceous chondrites, which are dominated by α-amino acids. Much higher amino acid abundances were found in the CM2 chondrites Murchison, Lonewolf Nunataks (LON) 94102, and Lewis Cliffs (LEW) 90500, the CR2 Elephant Moraine (EET) 92042, and the CR3 Queen Alexandra Range (QUE) 99177. For example, α-aminoisobutyric acid (α-AIB) and isovaline were approximately 100 to 1000 times more abundant in the type 2 and 3 chondrites compared to the more aqueously altered type 1 chondrites. Most of the chiral amino acids identified in these meteorites were racemic, indicating an extraterrestrial abiotic origin. However, nonracemic isovaline was observed in the aqueously altered carbonaceous chondrites Murchison, Orgueil, SCO 06043, and GRO 95577 with l-isovaline excesses ranging from approximately 11 to 19%, whereas the most pristine, unaltered carbonaceous chondrites analyzed in this study had no detectable l-isovaline excesses. These results are consistent with the theory that aqueous alteration played an important role in amplification of small initial left handed isovaline excesses on the parent bodies.

Identification of 3-sulfonylindazole derivatives as potent and selective 5-HT6 antagonists

As part of our efforts to develop agents for cognitive enhancement, we have been focused on the 5-HT6 receptor in order to identify potent and selective ligands for this purpose. Herein we report the identification of a novel series of 3-sulfonylindazole derivatives with acyclic amino side chains as potent and selective 5-HT6 antagonists. The synthesis and detailed SAR of this class of compounds are reported.

Bergman Cyclization of Acyclic Amino Acid Derived Enediynes Leads to the Formation of 2,3-Dihydrobenzo[f]isoindoles

Enediyne-peptide conjugates are recently recognized as useful tools in targeting various proteins, while the mechanism underlying the observed activity remains somewhat unclear. Addressing these issues, we have prepared acyclic amino acid derived enediynes and disclosed a novel thermally induced cyclization-elimination pathway. Initial formation of 1,4-benzene diradical and H-atom abstraction from an external donor is followed by S(N)2 substitution leading to 2,3-dihydrobenzo[f]isoindoles. The proposed mechanism is supported by experimental and computational data. Additionally, we showed that amino acid side chains, although placed three bonds away from acetylene terminuses, have an appreciable influence on the reactivity of studied enediynes. These results demonstrate that amino acid or peptide parts of enediyne-peptide conjugates cannot be considered as recognition elements exclusively but may also participate in various reactions through amine functionality.

ChemInform Abstract: The Stereochemical Outcome from Mitsunobu Couplings of Vicinal, N- Protected Acyclic Amino Alcohols.

Abstract Contrary to results expected in Mitsunobu reactions of amides derived from acyclic vic-amino alcohols (i.e., double inversion and hence, retention), urethane derivatives afford products solely of inversion.

Discovery of a Potent, Injectable Inhibitor of Aurora Kinases Based on the Imidazo-[1,2-a]-Pyrazine Core.

The imidazo-[1,2-a]-pyrazine (1) is a dual inhibitor of Aurora kinases A and B with modest cell potency (IC50 = 250 nM) and low solubility (5 μM). Lead optimization guided by the binding mode led to the acyclic amino alcohol 12k (SCH 1473759), which is a picomolar inhibitor of Aurora kinases (TdF K d Aur A = 0.02 nM and Aur B = 0.03 nM) with improved cell potency (phos-HH3 inhibition IC50 = 25 nM) and intrinsic aqueous solubility (11.4 mM). It also demonstrated efficacy and target engagement in human tumor xenograft mouse models.

Acyclic Amino Acids Catalyzed Direct Asymmetric Aldol Reactions in Aqueous Media Assisted by 2,4-Dinitrophenol

The catalytic capabilities of acyclic amino acids for the direct asymmetric aldol reactions assisted by 2,4-dinitrophenol in aqueous media were investigated. Several acyclic amino acids catalyzed asymmetric aldol reactions with excellent stereoselectivity, and afforded the corresponding β-hydroxy ketones in high yields and up to 99% ee. Our result suggested that the L-isoleucine was the most effective one. A systematic investigation of exploring the catalytic efficiency of natural acyclic amino acids for the asymmetric aldol reactions in aqueous media assisted by 2,4-dinitrophenol was reported. The result demonstrated that the L-isoleucine was the most effective one, which catalyzed asymmetric aldol reactions to afford the corresponding β-hydroxy ketones in high yields and up to 99% ee.

Facile Synthesis of a Family of H8BINOL-Amine Compounds and Catalytic Asymmetric Arylzinc Addition to Aldehydes

A family of optically active H(8)BINOL-AM compounds containing 3,3'-bis-tertiary amine substituents are synthesized by using a one-step reaction of H(8)BINOL with amino methanols that were in situ generated from various cyclic or acyclic secondary amines and paraformaldehyde. The H(8)BINOL-AM compounds are used to catalyze the reaction of functional arylzincs, in situ prepared from the reaction of aryliodides with ZnEt(2), with aldehydes to produce chiral diaryl carbinols and a few arylalkyl carbinols. Through this study, highly enantioselective catalysts were identified. It was found that the H(8)BINOL-AM compounds with sterically less congested cyclic or acyclic amino methyl substituents were more enantioselective than those with more bulky substituents. The pyrrolidinyl derivative (S)-12 in most cases showed greater enantioselectivity than other H(8)BINOL-AM compounds, especially for the challenging ortho-substituted aromatic aldehydes. A H(8)BINOL-AM with 3,3'-bis-sec-amine substituents, prepared by a multistep method, was also used to catalyze the arylzinc addition to aldehydes, but it showed enantioselectivity lower than that of the compounds with tertiary amine groups. It was found for the first time that an aryl bromide, 2-bromothiophene, could be used to prepare an arylzinc reagent by reaction with ZnEt(2). The addition of this heteroarylzinc reagent to an aldehyde in the presence of (S)-12 proceeded with good enantioselectivity.

Evolution of Proteins with Genetically Encoded “Chemical Warheads”

We recently developed a phage-based system for the evolution of proteins in bacteria with expanded amino acid genetic codes. Here we demonstrate that the unnatural amino acid p-boronophenylalanine (BF) confers a selective advantage in the evolution of glycan-binding proteins. We show that an unbiased library of naive antibodies with NNK-randomized V(H) CDR3 loops converges upon mutants containing BF when placed under selection for binding to a model acyclic amino sugar. This work represents a first step in the evolution of carbohydrate-binding proteins that use a reactive unnatural amino acid "warhead" and demonstrates that a "synthetic" genetic code can confer a selective advantage by increasing the number of functional groups available to evolution.

N-Acyldihydropyridones as Synthetic Intermediates. A Stereoselective Synthesis of Acyclic Amino Alcohols Containing Multiple Chiral Centers

Various multisubstituted piperidines containing a phenyl group at C-2 can be opened regio- and stereoselectively with cyanogen bromide. The ring-opened products contain useful cyanamide and benzylic bromide functional groups. The benzyl bromide can be cleanly reduced, or substituted with various nucleophiles via an S(N)2 process to add additional heteroatoms stereoselectively. This methodology is useful for the stereoselective synthesis of uniquely substituted alkylamine derivatives containing multiple chiral centers and various functionality. Diastereomerically pure amino alcohols containing three to five contiguous stereocenters were prepared using this strategy.

Synthesis of pyrrolo[3,4- b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5- c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4- b]pyrrole and its N-1–C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5- c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.

Aqua‐Organocatalyzed Direct Asymmetric Aldol Reaction with Acyclic Amino Acids and Organic Bases with Control of Diastereo‐ and Enantioselectivity.

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, please click on HTML or PDF.

Stereoselective Aldol Reacitons Catalyzed by Acyclic Amino Acids in Aqueous Micelles.

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, please click on HTML or PDF.

Aqua-organocatalyzed direct asymmetric aldol reaction with acyclic amino acids and organic bases with control of diastereo- and enantioselectivity

An effective aqua-organocatalytic direct aldol reaction is described. Aromatic amino acids can be a bifunctional catalyst system, which demonstrate excellent reactivity, diastereoselectivity, and enantioselectivity (up to 96% ee) in water without the addition of organic solvents. Furthermore, the present study demonstrates that both diastereo- and enantioselectivity can be easily modulated by the appropriate combination of an organocatalyst together with an organic base as a co-catalyst.