Beta-amino Alcohols Research Articles

Ring Opening of Epoxy Fatty Esters by Nucleophile to Form the Derivatives of Substituted <i>β</i>-Amino Alcohol

The nucleophilic ring opening of epoxy fatty esters was carried out using the amino-1,2,4-triazole to yield substituted derivatives of β-amino alcohol. The synthesis of the substituted beta amino alcohols has been achieved by refluxing equimolar quantities of long chain epoxy esters (epoxy fatty esters) and 4-amino-1,2,4-triazole in dichloromethane to yield following compounds, methyl 10-(4'-amino-1',2',4'-triazole)-11-hydroxy undecanoate (V), methyl 9-(4'-amino-1', 2',4'-triazole)-10-hydroxy octadecanoate (VI), methyl 9-(4'-amino-1',2',4'-triazole)-10,12-dihydroxy octadecanoate (VII), methyl 12-(4'-amino-1',2',4'-triazole)-9,13-dihydroxy octadecanoate (VIII). Epoxides of esters of fatty acids were obtained by reaction of esters of fatty acids with mchloroperbenzoic acid. All the newly synthesized compounds were characterized by IR, 1H NMR, 13C NMR and mass spectrometry.

Development of cationic polymer coatings to regulate foreign-body responses.

A library of cationic polymers, poly(beta-amino alcohols) with a great chemical diversity are synthesized using combinatorial polymerization. These polymers, when immobilized on a surface, drastically affect the behavior of monocyte/macrophage cells in vitro and early inflammatory reactions in vivo. Certain polymers are found capable of mitigating the foreign-body responses.

Chemical reactivity predictions: Use of data mining techniques for analyzing regioselective azidolysis of epoxides

Azidolysis of epoxides followed by reduction of the intermediate azido alcohols constitutes a valuable synthetic tool for the construction of beta-amino alcohols, an important chemical functionality occurring in many biologically active compounds of natural origin. However, depending on conditions under which the azidolysis is carried out, two regioisomeric products can be formed, as a consequence of the nucleophilic attack on both the oxirane carbon atoms. In this work, predictive models for quantitative structure-reactivity relationships were developed by means of multiple linear regression, k-nearest neighbor, locally weighted regression, and Gaussian Process regression algorithms. The specific nature of the problem at hand required the creation of appropriate new descriptors, able to properly reflect the most relevant features of molecular moieties directly involved in the opening process. The models so obtained are able to predict the regioselectivity of the azidolysis of epoxides promoted by sodium azide, in the presence of lithium perchlorate, on the basis of steric hindrance, and charge distribution of the substituents directly attached to the oxirane ring.

Lithiated Fluorinated Styrene Oxides: Configurational Stability, Synthetic Applications, and Mechanistic Insight

The configurational stability of some lithiated fluorinated styrene oxides has been investigated. Chemical studies have shown that in ethereal solvents alpha-lithiated ortho-, meta-, and para-fluorostyrene oxides (2-Li, alpha-5-Li, and alpha-6-Li) are all configurationally stable in the reaction time scale, whereas alpha-lithiated ortho-, meta-, and para-trifluoromethylstyrene oxides (9-Li, 13-Li, and 14-Li) are configurationally unstable. Optically active oxiranyllithiums 2-Li and 9-Li, could be stereospecifically generated and quenched with electrophiles. The corresponding derivatives were then successfully subjected to regiospecific ring-opening reactions with amines to give fluorinated beta-amino alcohols with a stereodefined quaternary carbinol center, which are useful synthons in medicinal chemistry. The barriers of inversion have been calculated (Eyring equation) for oxiranyllithiums 9-Li, 13-Li, and 14-Li by determining the enantiomeric ratios after electrophilic quenching on aging the enantioenriched organolithium for different times in THF; in the case of 9-Li, activation parameters have also been determined. Mechanisms that may be responsible of the racemization oxiranyllithiums 9-Li, 13-Li, and 14-Li undergo once generated are also discussed.

Enzymatic Synthesis of Enantiomerically Pure β‐Amino Ketones, β‐Amino Esters, and β‐Amino Alcohols with Baeyer–Villiger Monooxygenases

The enzymatic kinetic resolution of a broad set of beta-amino ketones was investigated by using a collection of 16 Baeyer-Villiger monooxygenases from different bacterial origins, which display various substrate specificities. Within this platform of enzymes excellent enantioselectivities (E>200) were found towards aliphatic and aromatic 4-amino-2-ketones, and some enzymes even showed opposite enantioselectivity. The intermediate beta-aminoalkyl acetates underwent autohydrolysis yielding optically pure beta-amino alcohols, which are key intermediates in the synthesis of natural products and bioactive compounds of high interest for the pharmaceutical industry. Furthermore, in some cases the abnormal esters were formed.

A 4‐Hydroxypyrrolidine‐Catalyzed Mannich Reaction of Aldehydes: Control of anti‐Selectivity by Hydrogen Bonding Assisted by Brønsted Acids

An anti-selective Mannich reaction of aldehydes with N-sulfonyl imines has been developed by using a 4-hydroxypyrrolidine in combination with an external Brønsted acid. The catalyst design is based on three elements: the alpha-substituent of the pyrrolidine, the 4-hydroxy group, and the Brønsted acid, the combination of which is essential for high chemical and stereochemical efficiency. The reaction works with aromatic aldehyde-derived imines, which have rarely been employed in previously reported enamine-based anti-Mannich reactions. Additionally, both N-tosyl and N-nosyl imines can be successfully used and the Mannich adducts can be easily reduced or oxidized, and after N-deprotection the corresponding beta-amino acids and beta-amino alcohols can be obtained with good yields. The results also show that this ternary catalytic system may be practical in other enamine-based reactions.

Microwave-assisted regioselective ring opening of non-activated aziridines by lithium aluminium hydride

A new synthetic protocol for the LiAlH(4)-promoted reduction of non-activated aziridines under microwave conditions was developed. Thus, ring opening of 2-(acetoxymethyl)aziridines provided the corresponding beta-amino alcohols, which were then used as eligible substrates in the synthesis of 5-methylmorpholin-2-ones via condensation with glyoxal in THF. The same procedure was applied for the preparation of novel 5(R)- and 5(S)-methylmorpholin-2-ones starting from the corresponding enantiopure 2-(hydroxymethyl)aziridines. Additionally, 2-(methoxymethyl)- and 2-(phenoxymethyl)aziridines were treated with LiAlH(4) under microwave irradiation, giving rise to either isopropylamines or 1-methoxypropan-2-amines depending on the reaction conditions.

Rearrangement of β-amino alcohols via aziridiniums: a review

This tutorial review focuses on the rearrangement of beta-amino alcohols via aziridinium intermediates. It covers the literature from 1947 to January 2009 (55 references). The rearrangement of beta-amino alcohols can be performed by activation of the hydroxy group followed by the addition of nucleophiles (Nu). In most examples, an aziridinium intermediate is involved in the rearrangement. The ratio of amines resulting from the attack of nucleophiles at either the C-1 or C-2 position of the aziridinium intermediate, depends on the nature of the nucleophiles and the R(2) substituent. In some cases, solvent as well as temperature can influence the ratio of amines.

Efficient Synthesis of Functionalized Aziridinium Salts

Various aziridinium salts were efficiently prepared from bromination of a series of backbone substituted N,N-bisubstituted beta-amino alcohols and isolated via flash column chromatography. The effect of C-substitution, N-substitution, solvent, leaving group, and counteranions on formation of the isolable aziridinium salts was investigated.

Al(OTf)3-Mediated Epoxide Ring-Opening Reactions: Toward Piperazine-Derived Physiologically Active Products

Al(OTf)(3) is a good catalyst for the ring opening of epoxides, forming beta-amino alcohols bearing the piperazine motif. Two different strategies were examined, where the glycidyl ether resided on one-half of the molecule or the other, allowing insight into a best-case approach for the ring-opening step. Each half of the molecule contained an heteroatom that could be used either to attach the glycidyl moiety or as the nucleophile in the ring-opening reaction, for the same set of reagents, allowing this approach.

Palladium-Catalyzed Cyclization of Unsaturated β-Amino Alcohols: A New Access to Enantiopure Bicyclic Oxazolidines

Chiral unsaturated beta-amino alcohols possessing a dialkylamino function cyclize in the presence of Pd(II) catalysts and reoxidants to afford enantiopure bicyclic oxazolidines with total regio- and stereocontrol. The scope and limitations of this transformation have been studied.

Highly Enantioselective Synthesis of Linear β‐Amino Alcohols

Beta-amino alcohols derived from alpha-amino acids have been extensively used as a powerful source of chirality. Transforming the alcohol moiety into a good leaving group has allowed the rearrangement of these beta-amino alcohols and the introduction of a large number of nucleophiles through the anchimeric participation of the nitrogen atom. An overview on the recent progress realized on the rearrangement of these beta-amino alcohols in the presence of (CF(3)CO)(2)O and H(2)SO(4) is reported.

Stable Aziridinium Salts as Versatile Intermediates: Isolation and Regio- and Stereoselective Ring-Opening and Rearrangement

Rock trapping and exploration: Aziridinium bromide salts were discovered serendipitously during bromination of N,N-dicarboxymethylated beta-amino alcohols. Regiospecific ring-opening and rearrangement of the isolated, surprisingly stable aziridinium salts produces useful molecules including C-functionalized oxomorpholines and alpha,beta-unsaturated amines.

Non Lewis acid catalysed epoxide ring opening with amino acid esters

The ring opening of epoxides by various amino acid esters is described in refluxing trifluoroethanol without any catalyst. Under these simple conditions the corresponding beta-amino alcohols are obtained in good to excellent yields in relatively short reaction times compared to previously reported methods.

Application of kinetic resolution using HCS as chiral auxiliary: Novel synthesis of β‐blockers (S)‐betaxolol and (S)‐metoprolol

Optically pure (S)-betaxolol and (S)-metoprolol were prepared with an extremely facile and practical method using kinetic resolution of beta-amino alcohols employing HCS as chiral auxiliary. High enantiomeric purity (ee > 99%) was achieved and the synthetic strategy is amenable to industrial scale-up.

Syntheses of (S,S)-Reboxetine via a Catalytic Stereospecific Rearrangement of β-Amino Alcohols

The formal total synthesis of (S,S)-reboxetine has been realized by two different approaches using a stereospecific rearrangement of beta-amino alcohols catalyzed by (CF3CO)2O.

Design of Organocatalysts for Asymmetric Direct Syn-Aldol Reactions

Two new organocatalysts 3a and 3b, derived from L-leucine and (S)-beta-amino alcohols that were prepared from L-valine, were designed and afforded the direct syn-aldol reactions of a wide scope of aldehydes with various ketones with an excellent diastereomeric ratio of up to >20/1 and enantioselectivities of up to 99% ee.

Microwave-Assisted Ring Opening of Epoxides: A General Route to the Synthesis of 1-Aminopropan-2-ols with Anti Malaria Parasite Activities

A series of 1-aminopropan-2-ols were synthesized and evaluated against two strains of malaria, Plasmodium falciparum FCR3 (chloroquine-resistant) and 3D7 (chloroquine-sensitive). Microwave-assisted ring opening of epoxides (aryl and alkyl glycidyl ethers, glycidol, epichlorohydrin) with various amines without catalysts generated the desired library of beta-amino alcohols rapidly and efficiently. Most of the compounds showed micromolar potency against malaria, with seven of them having IC50 values between 1 and 10 microM against both Plasmodium falciparum strains.

Suzuki Cross-Coupling on Enantiomerically Pure Epoxides: Efficient Synthesis of Diverse, Modular Amino Alcohols from Single Enantiopure Precursors

Suzuki arylation of enantiopure (4-bromophenyl)- or (3,5-dibromophenyl)glycidyl ethers has been achieved in toluene under Buchwald conditions [ArB(OH)2 (1.1 equiv), Cs2CO3 (2 equiv), Pd2(dba)3.C6H6 (1 mol %), S-Phos (4 mol %), toluene, 100 degrees C] allowing for the formation of modular arylglycidyl ethers not directly available in enantiopure form by epoxidation routes. These bulky ethers, when submitted to regioselective and stereospecific ring opening with ammonia [aq NH3, LiClO4 (1 equiv), THF, microwave irradiation (80 W), 125 degrees C] in a sealed tube, provide access to novel enantiopure beta-amino alcohols which, in turn, provide an easy access to structurally complex C2 symmetrical bisoxazolines.

Dimethylzinc‐Mediated, Enantioselective Synthesis of Propargylic Amines

A one-pot, enantioselective synthesis of N-aryl propargylic amines, using alkynylation reagents obtained from dimethylzinc and terminal acetylenes in combination with various aldehydes and o-methoxyaniline as starting materials, has been developed. Enantiopure beta-amino alcohols derived from norephedrine were used as non-covalent chiral auxiliaries, both in stoichiometric or substoichiometric amount. After optimization, propargylic amines were obtained in good to high yields (up to 93%) and with moderate to high enantiomeric excesses (up to 97% ee). The possibility to recover the chiral auxiliary after the reaction was demonstrated.