Β-amino Alcohol Derivatives Research Articles

Synthesis of N-Aryl β-Amino Alcohols by Trifluoroacetic Acid Promoted Multicomponent Coupling of Aziridines, Arynes, and Water.

A transition-metal-free, three-component coupling involving N-substituted aziridines, arynes, and water promoted by trifluoroacetic acid (TFA) has been reported. The reaction furnished medicinally important N-aryl β-amino alcohol derivatives in moderate to good yields. In addition, the use of azetidines in this reaction afforded N-aryl γ-amino alcohol derivatives.

ChemInform Abstract: Trapping of Carboxylic Oxonium Ylides with N‐Boc Imines for the Facile Synthesis of β‐Amino Alcohol Derivatives.

A Rh2(OAc)4-catalyzed three-component reaction of carboxylic acids, α-diazoacetophenones, and N-Boc imines has been developed to efficiently produce β-amino alcohol derivatives. Oxonium ylides generated from carboxylic acids and metal carbenoids have been intercepted by electrophiles for the first time.

Trapping of Carboxylic Oxonium Ylides with N-Boc Imines for the Facile Synthesis of β-Amino Alcohol Derivatives

A Rh₂(OAc)₄-catalyzed three-component reaction of carboxylic acids, α-diazoacetophenones, and <i>N</i>-Boc imines has been developed to efficiently produce β-amino alcohol derivatives. Oxonium ylides generated from carboxylic acids and metal carbenoids have been intercepted by electrophiles for the first time.

Synthesis of β-amino alcohol derivatives from phenols in presence of phase transfer catalyst and lipase biocatalyst

Article history: Received June 25, 2012 Received in Revised form November 6, 2012 Accepted 6 November 2012 Available online 6 November 2012 A simple and environmentally friendly reaction has been developed for the first time for onepot synthesis of β-amino alcohol derivatives from aromatic phenols, epichlorohydrin and amines by using phase transfer catalysts (PTC) and Aspergillus Oryzae lipase biocatalyst. This method provides access to pharmaceutically relevant products in excellent yields with high regioselectivity. The remarkable catalytic activity and reusability of lipase was possible up to four consecutive cycles. © 2013 Growing Science Ltd. All rights reserved.

Synthesis of Aminoquinoline‐Based Aminoalcohols and Oxazolidinones and Their Antiplasmodial Activity

Novel aminoquinoline β-aminoalcohol and oxazolidinone derivatives were designed, synthesized, and evaluated for in vitro antiplasmodial activity against a chloroquine-sensitive (3D7) and chloroquine-resistant (K1) strains of Plasmodium falciparum. A few β-aminoalcohol derivatives were more potent than chloroquine against chloroquine-sensetive Plasmodiums. The potency of these derivatives decreased against chloroquine-resistant species in all cases (higher resistance indices), suggesting a possible cross-resistance between this group of compounds and chloroquine which could be due to their structural similarity. Although changing β-aminoalcohols to their oxazolidinone counterparts decreased the potency in all the cases, the compounds were still active and the resistance indices for these compounds improved significantly in comparison with those of β-aminoalcohols. This may indicate the absence of cross-resistance between these new derivatives and chloroquine.

Synthesis, biological evaluation and mechanistic studies of totarol amino alcohol derivatives as potential antimalarial agents

Herein we report on the semisynthesis and biological evaluation of β-amino alcohol derivatives of the natural product totarol and other simple aromatic systems. All β-amino alcohol derivatives of totarol exhibited higher antiplasmodial activity than totarol [IC50: 11.69μM (K1, chloroquine and multi-drug resistant strain), and 11.78μM (D10, chloroquine sensitive strain)]—12e was the most active [IC50: 0.63μM (K1), and 0.61μM (D10)]. The phenyl and naphthyl β-amino alcohol derivatives were much less active than their corresponding totarol equivalents. The majority of the β-amino alcohol derivatives of totarol were more active against K1 than the D10 strains of Plasmodium falciparum, a trend similar to the inverse relationship observed with the established aryl-amino alcohol antimalarial mefloquine. Selected compounds were shown to affect erythrocyte morphology, inhibit erythrocyte invasion and trigger CQ accumulation.

Development of β-amino alcohol derivatives that inhibit Toll-like receptor 4 mediated inflammatory response as potential antiseptics.

Toll-like receptor 4 (TLR4) induced proinflammatory signaling has been directly implicated in severe sepsis and represents an attractive therapeutic target. Herein, we report our investigations into the structure-activity relationship and preliminary drug metabolism/pharmacokinetics study of β-amino alcohol derivatives that inhibit the TLR4 signaling pathway. Lead compounds were identified from in vitro cellular examination with micromolar potency for their inhibitory effects on TLR4 signaling and subsequently assessed for their ability to suppress the TLR4-induced inflammatory response in an ex vivo whole blood model. In addition, the toxicology, specificity, solubility, brain-blood barrier permeability, and drug metabolism of several compounds were evaluated. Although further optimizations are needed, our findings lay the groundwork for the future drug development of this class of small molecule agents for the treatment of severe sepsis.

Design, synthesis and cytotoxic activities of novel β-amino alcohol derivatives

Three series of novel β-amino alcohols possessing an N-anthranyl group have been obtained using tryptophan as the major starting material. These compounds were screened for cytotoxic activity against five human cancer cell lines in vitro by MTT assay, and some of them exhibited potential ability to be anticancer agents. Structure-activity relationship was carefully investigated. Only the compounds possessing small substituents (H or CH(3)) at C-6 position showed the same activity as cisplatin (DDP) did.

Glycerine and CeCl3˙7H2O: An Efficient and Recyclable Reaction Medium for Ring Opening of Epoxides with Thioamides and Amines

Oxiranes undergo rapid ring-opening reaction with a range of thioamides and amines to afford the corresponding β-amino alcohol derivatives. The reactions were carried out using glycerine and cerium(III) chloride as a recyclable reaction medium. All the reactions were carried out at room temperature and the products were obtained in excellent yields.

ChemInform Abstract: Synthesis of Chiral N-Protected β-Amino Alcohols by the Use of UNCAs.

Abstract A facile synthesis of a wide variety of N-protected β-amino alcohol derivatives under mild conditions is described. N-urethane protected amino acid N-carboxyanhydrides (UNCAs) were used as starting material and reduced into the corresponding alcohols with the appropriate hydride, sodium borohydride. The reaction is simple, unexpensive, easily scaled up, and proceeds without observable racemization.

Strict Reagent Control in the Asymmetric Allylboration of N-TIPS-α-Amino Aldehydes with the B-Allyl-10-TMS-9-borabicyclo[3.3.2]decanes

The allylboration of enantiomerically pure N-triisopropylsilyl-alpha-amino aldehydes (2) with B-allyl-10-trimethylsilyl-9-borabicyclo[3.3.2]decanes (1) proceeds cleanly at -78 degrees C, exhibiting essentially complete reagent control. After an oxidative workup, an HOAc-mediated N-->O TIPS rearrangement facilitates the clean formation of stable O-TIPS protected beta-amino alcohol derivatives 3 which are isolated in 60-83% yields in > or = 96% de and > 99% ee. For the leucinal series (R = i-Bu), an efficient entry to either statine (8aSS) or epi-statine (8aRS) is reported illustrating the versatility of this potent 1/2 combination.

Synthesis of limonene β-amino alcohol derivatives in support of new antileishmanial therapies

A series of seven limonene beta-amino alcohol derivatives has been regioselectively synthesised in moderate to good yields. Two of these compounds were found to be significantly effective against in vitro cultures of the Leishmania (Viannia) braziliensis promastigote form in the micromolar range. The activities found for 3b and 3f were about 100-fold more potent than the standard drug, Pentamidine, in the same test, while limonene did not display any activity. This is the first report of antileishmanial activity by limonene beta-amino alcohol derivatives.

Acaricidal activity of limonene, limonene oxide and β-amino alcohol derivatives on Rhipicephalus ( Boophilus) microplus

Limonene, limonene oxide and eight β-amino alcohol derivatives obtained by synthesis were investigated for the effect on egg hatchability and mortality rates of newly hatched larvae of the cattle tick Rhipicephalus ( Boophilus) microplus. At the doses between 10 μg/ml and 2.5 μg/ml all the compounds were highly lethal to the larvae and some of them showed activity at lower concentrations. The effect on the eggs hatchability was observed in all the treatments.

Approach to a better understanding and modeling of ( S)-dihydrofuran-2-yl, ( S)-tetrahydrofuran-2-yl-, and furan-2-yl-β-dialkylaminoethanol ligands for enantioselective alkylation

This paper outlines our efforts to study the influence of an oxygen atom adjacent to the stereogenic center of β-aminoalcohol derivatives used as ligands for catalysts in the asymmetric alkylation of aldehydes. Thirty-four enantiomerically pure ( S)-dihydrofuran-2-yl, ( S)-tetrahydrofuran-2-yl-, and furan-2-yl-β-dialkylamino alcohols have been prepared from 1,4:3,6-dianhydromannitol, 1,4:3,6-dianhydrosorbitol, and aminoacids, and then have been evaluated as ligands for the enantioselective addition of diethylzinc to benzaldehyde. Attention has been focused on the structural features governing the extent of chiral induction, the reaction rate, and the chemical yield of 1-phenyl-1-propanol which has been promoted by this wide collection of β-dialkylamino alcohols.

Ir-Catalyzed Allylic Amination/Ring-Closing Metathesis: A New Route to Enantioselective Synthesis of Cyclic β-Amino Alcohol Derivatives

Ir-catalyzed allylic aminations of (E)-4-benzyloxy-2-butenyl methyl carbonate with benzylamine using Feringa's (Sa,Sc,Sc)-phosphoramidite as a chiral ligand afforded linear-aminated achiral product N,O-dibenzyl-4-amino-2-buten-1-ol regioselectively (linear/branched = >99/1), whereas the (E)-5-benzyloxy-2-pentenyl methyl carbonate showed completely opposite regioselectivity (linear/branched = >1/99) and afforded the optically active (3R)-N,O-dibenzylated 3-amino-1-penten-5-ol with very high enantioselectivity (96% ee), which was used as a key intermediate for the effective synthesis of various cyclic beta-amino alcohol derivatives through ring-closing metathesis in high yields.

Synthesis of enatiomerically enriched β-amino alcohol derivatives via chiral base mediated-asymmetric deprotonation of (benzyl methyl ether) tricarbonylchromium(0) complex and electrophilic trapping with imines

Deprotonation of (benzyl methyl ether)tricarbonylchromium(0) complex 1 by chiral base 2 followed by quenching reaction with imines 3 and subsequent decomplexation give β-amino alcohol derivatives 5 in good yields and high enantioselectivities (up to 96% e.e.).

Synthesis of totarol amino alcohol derivatives and their antiplasmodial activity and cytotoxicity

The previously unknown antiplasmodial activity of the plant derived natural product totarol is reported. Novel β-amino alcohol derivatives based on this natural product were designed, synthesised and evaluated for in vitro antiplasmodial activity and cytotoxicity. These derivatives showed antiplasmodial IC 50 values in the range of 0.6–3.0 μM and were equally active against a chloroquine-sensitive and resistant strain of Plasmodium falciparum, while showing little cytotoxicity against a mammalian cell line (CHO). In terms of lead development, two of the compounds based on substituted phenylpiperazine warrant further investigation as potential antiplasmodial leads. In addition to their selective antiplasmodial activity and lack of chloroquine cross-resistance, these compounds are structurally different to any of the available antimalarial drugs.

Synthesis of enantiomerically enriched β-amino alcohol derivatives via asymmetric lithiation of O-benzyl carbamates–imine addition using (−)-sparteine complexes

The asymmetric lithiation of O-benzyl carbamates–imine addition sequence using sec-butyllithium/(−)-sparteine complexes has been studied. The reactions proceed with high diastereoselectivity, giving the threo β-amino alcohol derivatives with modest to good e.e. The best enantioinduction was obtained with O-benzyl carbamates bearing methoxy substituents on the aromatic ring.

ChemInform Abstract: Catalytic Activation of Imine Derivatives Using Novel Lewis Acids

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 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.

新しいルイス酸を用いるイミン類の触媒的活性化

The Lewis acid-mediated reactions of imine are one of the most powerful methods for preparation of nitrogen-containing compounds. However, there are few examples of the reactions using catalytic amounts of Lewis acids, because the strong coordination of the products (which are mostly secondly or tertiary amines), deactivates the acids. This article introduces several types of new achiral and chiral Lewis acids which can mediated the reactions of imines catalytically. The essence of the catalytic activation of imines by Lewis acids is the equilibrium between Lewis acids and bases (imines or products), and it has been revealed that rare earth triflates (lanthanide and scandium trifluoromethanesulfonate) are excellent catalysts for this purpose. Imino-aldol reactions, aza Diels-Alder reactions, allylation reactions, cyanation reactions, and three-component reactions of aldehydes, amines, and nucleophiles were successfully carried out in the presence of catalytic amounts of rare earth triflates. Polymer-supported reagents also worked well by using the triflates as catalysts. In addition, it was shown that group IV triflates (Zr and Hf triflates) were effective for catalytic activation of imines. The first truly catalytic asymmetric reactions of imines have been achieved using new chiral Lewis acids. In the presence of a catalytic amount of a chiral rare earth catalyst, imines derived from 2-aminophenol and aldehydes reacted with cyclopentadiene or vinyl ethers to afford 8-hydroxytetrahydroquinoline derivatives in high yields with high diastereo- and enantioselectivities. Moreover, the first catalytic enantioselective Mannich-type reactions of imines with silyl enolates using a novel chiral zirconium catalyst have been developed. High levels of enantioselectivities in the synthesis of chiral β-amino ester derivatives, β-amino alcohol derivatives, and tetrahydropyridine derivatives have been achieved using these reactions.