Α-hydroxy Amides Research Articles

Flexible and Chemoselective Oxidation of Amides to α-Keto Amides and α-Hydroxy Amides.

A suite of flexible and chemoselective methods for the transition-metal-free oxidation of amides to α-keto amides and α-hydroxy amides is presented. These highly valuable motifs are accessed in good to excellent yields and stereoselectivities with high functional group tolerance. The utility of the method is showcased by the formal synthesis of a potent histone deacetylase inhibitor.

Condensation of Vilsmeier Salts, Derived from Tetraalkylureas, with α-Hydroxy Amide Derivatives: One-pot Approach to Synthesize 2-Dialkylamino-2-oxazolin-4-ones

A novel and straightforward synthetic protocol was developed to synthesize 2-dialkylamino-2-oxazolin-4-ones from various Vilsmeier salts and α-hydroxy amides derivatives. Notably, thozalinone (3a), as a mild stimulant in tristimania and anorexic, could be synthesized simply and in a high yield using this methodology.

Zinc-catalyzed chemoselective alkylation of α-keto amides with 2-alkylazaarenes.

A zinc-catalyzed C(sp3)-H addition of 2-alkylazaarenes to α-keto amides to furnish azaarene incorporated α-hydroxy amides has been developed with a wide range of substrates in moderate to excellent yields, respectively. Chemoselective alkylation of the keto functionality of the α-keto amides in the presence of simple ketones is the key advantage of this Zn-catalyzed transformation. This approach has been demonstrated to one gram-scale synthesis. 1H NMR and D2O exchange experimental studies reveal that the reaction proceeds through a Zn-enamide intermediate.

ChemInform Abstract: Ru(III)‐Mediated Intramolecular ortho‐C(sp2)—H Activation/Oxidative Acylation: One‐Pot Synthesis of Isatins from α‐Hydroxy Amides.

Abstract A novel and efficient synthesis of isatins from α-hydroxy amides via ruthenium-mediated aromatic C–H activation is described. The reactions proceeded smoothly under mild conditions and generated the corresponding products in good to excellent yields. This methodology has a broad substrate scope and opens up an interesting and attractive avenue for the application of intramolecular ortho-C–H activation.

ChemInform Abstract: IBX‐Promoted Domino Reaction of α‐Hydroxy Amides: A Facile One‐Pot Synthesis of Isatins.

A novel and temperature-controlled oxidation of α-hydroxy amides in the presence of IBX is described. The divergent one-pot synthesis of isatins and α-formyl amides was achieved in good to excellent yields under metal-free conditions. And these two mild methods can tolerate a variety of functional groups, and are operationally simple.

Ru(III)-mediated intramolecular ortho-C(sp2)–H activation/oxidative acylation: one-pot synthesis of isatins from α-hydroxy amides

A novel and efficient synthesis of isatins from α-hydroxy amides via ruthenium-mediated aromatic C–H activation is described. The reactions proceeded smoothly under mild conditions and generated the corresponding products in good to excellent yields. This methodology has a broad substrate scope and opens up an interesting and attractive avenue for the application of intramolecular ortho-C–H activation.

ChemInform Abstract: Enantioselective Synthesis of α‐Hydroxy Amides and β‐Amino Alcohols from α‐Keto Amides.

Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral Cu(II)/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives.

Copper-Catalyzed Synthesis of Chiral α-Hydroxy Amides and β-Amino Alcohols

Copper-Catalyzed Synthesis of Chiral α-Hydroxy Amides and β-Amino Alcohols

IBX-promoted domino reaction of α-hydroxy amides: a facile one-pot synthesis of isatins

A novel and temperature-controlled oxidation of α-hydroxy amides in the presence of IBX is described.

Enantioselective Synthesis of α-Hydroxy Amides and β-Amino Alcohols from α-Keto Amides.

Synthesis of enantiomerically enriched α-hydroxy amides and β-amino alcohols has been accomplished by enantioselective reduction of α-keto amides with hydrosilanes. A series of α-keto amides were reduced in the presence of chiral Cu(II)/(S)-DTBM-SEGPHOS catalyst to give the corresponding optically active α-hydroxy amides with excellent enantioselectivities by using (EtO)3SiH as a reducing agent. Furthermore, a one-pot complete reduction of both ketone and amide groups of α-keto amides has been achieved using the same chiral copper catalyst followed by tetra-n-butylammonium fluoride (TBAF) catalyst in presence of (EtO)3SiH to afford the corresponding chiral β-amino alcohol derivatives.

Synthesis of α-Hydroxy Amides

α-Hydroxy amides are a class of important intermediates in organic synthesis. It plays an important role in the field of science and medicine. However, the preparation methods of α-hydroxy amides are relatively few, and they are usually enzyme-or Lewis acid-catalyzed reactions. These types of methods are not ideal in operation, yield and/or stereoselectivity. We found a new way to synthesize α-hydroxy amides by transforming amino acids into α-hydroxyl acids, and then by amination of the α-hydroxy acids.

ChemInform Abstract: α‐Hydroxy Amides from Carbamoylsilane and Aldehydes.

ChemInform Abstract: α‐Hydroxy Amides from Carbamoylsilane and Aldehydes.

Chemoselective reduction of α-keto amides using nickel catalysts.

Ni-catalysts are used for the first time to synthesize highly important α-hydroxy amides and β-amino alcohols from α-keto amides by chemoselective and complete reduction using hydrosilanes. Chemoselective complete reduction of α-keto amides in the presence of a simple amide group is a key benefit of these Ni-catalysts.

Metal free chemoselective reduction of α-keto amides using TBAF as catalyst

Metal and ligand free chemoselective reduction of keto group and complete reduction of the both keto and amide groups of α-keto amide with hydrosilanes using tetrabutylammoniumflouride (TBAF) as catalyst have been accomplished. This methodology affords an efficient and economic route for the synthesis of biologically important α-hydroxy amides and β-amino alcohols.

Biocatalytic reduction of α-keto amides to (R)-α-hydroxy amides using Candida parapsilosis ATCC 7330

Biocatalytic reduction of primary and secondary α-keto amides was accomplished using whole cells of Candida parapsilosis ATCC 7330. The primary (R)-α-hydroxy amides were obtained in good enantiomeric excess (up to 94%) and conversion (88–99%) as compared to the secondary (R)-α-hydroxy amides.

Cyanohydrin Hydration with [Ru(η6-p-cymene)Cl2PR3] Complexes

The catalytic hydration of cyanohydrins to their corresponding α-hydroxyamides provides a route to industrially useful α-hydroxy amides, α-hydroxy esters, α-hydroxy carboxylic acids, and their acry...

Chiral calix[4]arenes bearing α-hydroxy amide units as membrane carriers for amino acid methyl esters

Novel chiral calix[4]arene derivatives functionalized at the lower rim have been prepared from the reaction of p-tert-butylcalix[4]arene diamine or acylhydrazine derivative with mandelic acid or hydroxyisovaleric acid. The structures of these receptors were characterized by FTIR, 1H, 13C and 2D COSY NMR spectroscopy and elemental analysis. The transport of amino acid derivatives (phenylalanine, phenylglycine and tryptophan methyl ester hydrochlorides) was studied through bulk liquid membrane in the presence of chiral calix[4]arene derivatives. The receptors have been found to act as carriers for transport of aromatic amino acid methylesters from the aqueous source phase to the aqueous receiving phase. The transport rate and L/D selectivity of amino acid esters studied depend strongly upon the structure of the chiral receptors and guests. The best enantioselectivity was obtained in the case of phenylglycine methyl ester for all chiral carriers.

QSAR based modeling on a series of α-hydroxy amides as a novel class of bradykinin B1 selective antagonists

G-protein coupled receptors like Bradykinin (BK) B1 represent a potential treatment route for chronic pain and inflammation. Quantitative structure activity relationship has been performed on a series of α-hydroxy amides as a novel class of bradykinin B1 selective antagonists, using different physicochemical parameters along with appropriate indicator variables. It has been found that physicochemical parameters such as connectivity indices 3χ, 4χ and 5χ, molecular weight, molar refractivity, density along with indicator variables are significantly correlated with activity. In this paper best results were obtained by using multiple regression analysis. Different models were generated with high values of R2 and low values of PRESS/SSY ratio. The significant equations were statistically tested by using leave one out (LOO) technique and cross validation methods.

ChemInform Abstract: A One-Pot Procedure for the Synthesis of α-Hydroxy Amides from the Corresponding α-Hydroxy Acids.

ChemInform Abstract: A One-Pot Procedure for the Synthesis of α-Hydroxy Amides from the Corresponding α-Hydroxy Acids.

ChemInform Abstract: A Novel Deoxygenation of Hydroxy Groups Activated by a Vicinal Carbonyl Group via Reaction with Ph3P/I2/Imidazole.

Abstract A new procedure for a direct conversion of an α-hydroxy sugar ester, lactone or amide into the corresponding α-deoxyester, lactone or nitrile using the system Ph3/I2/imidazole is reported. Its efficiency is illustrated by deoxygenation in good yields at position 2 of methyl 3,4:5,6-di-O-isopropylidene-D-gluconate (1), and at positions 5 of 3-O-benzyl-1,2-O-isopropylidene-α-D-glucofuranuronamide (3) and 1,2-O-isopropylidene-α-D-glucofuranurono-6,3-lactone (5). Reaction with 5,6-O-isopropylidene-L- and-D-gulo-1,4-lactones (7) and (9), respectively, afforded the corresponding α,β-unsaturated lactones in good yields. 1. Presented at the XVIIIth International Carbohydrate Sympmium, Milan, Italy, July 21–26, 1996. 2. Dedicated to Prof Hans Paulsen's 75th. birthday.