Acetyl Migration Research Articles

Microwave-assisted 1,3-dipolar cycloaddition reactions of vinylic glycosides with aryl azides – unexpected synthesis of triazoles and acetyl group migration

The synthesis of sugar-derived triazolines was attempted under microwave irradiation, by 1,3dipolar cycloaddition to azides. However, due to the “push-pull” nature of the dipolarophile, we have obtained triazoles by elimination of the sugar unit, which then has one free hydroxyl group at a selective carbon position. The triazoles obtained are important precursors of anticonvulsive drugs. Furthermore, we have observed that under microwave irradiation of 300W it is possible to promote acetyl group migration to a free hydroxyl group within the carbohydrate moiety.

AcOLeDMAP and BnOLeDMAP: Conformationally Restricted Nucleophilic Catalysts for Enantioselective Rearrangement of Indolyl Acetates and Carbonates

The rate of indolyl O- to C-acetyl or carboxyl rearrangement is accelerated by the electron-withdrawing N-diphenylacetyl group (DPA) using the conformationally restricted chiral catalysts AcOLeDMAP (12b) and BnOLeDMAP (13b). Highly enantioselective conversion to quaternary C-acetylated and C-carboxylated oxindoles is observed, even for substrates containing branched substituents. The rearrangement of the carboxylate substrates 19 occurs with complementary enantiofacial selectivity using catalyst 13b compared to the acetyl migrations of 16 catalyzed by 12b. Access to N-unsubstituted oxindoles is demonstrated by DPA cleavage with Et(2)NH.

Synthesis of Simple Adenosine Diphosphate Ribose Analogues

The synthesis of analogues of adenosine diphosphate ribose and acetylated adenosine diphosphate ribose, modified at the northern pentose, is reported. The stereochemistry at the acetylated centers was chosen to minimize acetyl migration and dictated the overall synthetic strategy.

Regioselective synthesis of 4azido-Neu2en5,7Ac 21Me and its intramolecular transformation to 4azido-Neu2en5,9Ac 21Me

Methyl 5- N-acetyl-7- O-acetyl-4-azido-2,3-didehydro-2,4-dideoxy-neuraminic acid (4azido-Neu2en5,7 Ac 21Me) was synthesized regioselectively starting from 4azido-Neu2en5Ac1Me in high yield. The transformation of 4azido-Neu2en5,7Ac 21Me to the corresponding thermodynamically stable 4azido-Neu2en5,9Ac 21Me via intramolecular acetyl migration was confirmed by single-crystal X-ray diffraction analysis. The proposed rearrangement mechanism is discussed.

Novel Catalytic Synthetic Route to Protected α-Methyl Threonine and the First Asymmetric Acetyl Migration in a Steglich Rearrangement Reaction

A short synthetic route to protected a-methyl threonine 5 as a representative example for (protected) a-methylated a-amino-b-hydroxy acids bearing a stereogenic quaternary carbon center in a-position was developed. This multistep synthesis is based on the use of an easily accessible prochiral starting material in the presence of an organocatalyst, and allows the access to all four types of stereoisomers. In addition, the first enantioselective acetyl migration in a Steglich rearrangement reaction as a key step in this multistep synthesis of 5 was achieved. The heterocycle 12, which was used in Steglich rearrangement reaction for the first time, turned out to be an efficient organocatalyst leading to an enantioselectivity of up to 63% ee.

Photochromic crown‐containing molecular switches of chemosensor activity

AbstractThe crown‐ether functionalized 2‐(N‐acetyl‐N‐arylaminomethylene)benzo[b]thiophene‐3(2H)‐ones exhibit photochromic behavior involving photoinitiated Z/E‐isomerization around the exocyclic CC bond followed by a fast thermal N → O acetyl migration and syn → anti isomerization of the resulting kinetically stable O‐acetyl isomers. The reverse rearrangement is an acid catalyzed reaction. The addition of alkali‐earth metal ions to solutions of N‐acyl isomers induces negligible changes in their UV/Vis spectra, which can be significantly enhanced after irradiation and conversion to the O‐acyl isomers. The compounds obtained may be used as sensitive photodynamic chemosensors with the ‘off‐on’ mechanism for alkali‐earth ions (Ca2+, Ba2+). Quantum‐chemical calculations using the DFT B3LYP/LanL2DZ method predict greater affinity of these sensors to Ca2+ ions (in the gas phase) and to Ba2+ ions (in acetonitrile). Copyright © 2007 John Wiley & Sons, Ltd.

Regio- and stereoselective anomeric esterification of glucopyranose 1,2-diols and a facile preparation of 2-O-acetylated glucopyranosyl trichloroacetimidates from the corresponding 1,2-diols

A highly regio- and stereoselective anomeric esterification of 3- O-allyl (or benzyl, or benzoyl)-4,6- O-isopropylidene-α,β- d-glucopyranose with acetyl chloride, or allyl chloroformate, or ethyl chloroformate gave the corresponding 2-OH, 1-β-acetates or -carbonates in excellent yields. The 2-OH, 1-β-acetates were readily converted to the corresponding 2-O-acetylated glucopyranosyl trichloroacetimidates by reaction with trichloroacetonitrile via base promoted acetyl migration, while the 2-OH, 1-β-carbonates were good glycosyl acceptors for the synthesis of (1→2)-linked oligosaccharides.

Synthesis and evaluation of glycosyl donors with novel leaving groups for transglycosylations employing β-galactosidase from bovine testes

Novel aryl β- d-galactopyranosides were synthesized employing phase-transfer catalysis, and assayed as potential galactose donors in the presence of β-galactosidase from bovine testes using pNP-Gal as a reference. The aglycones were represented mainly by nitrophenols containing halogens, hydroxymethyl, aldehyde, carboxyl, ester or amino functions. An unusual intermolecular acetyl migration onto the benzylic alcohol group was observed during galactosylation of hydroxymethylnitrophenols. Pyridyl glycosides were obtained by reaction with the corresponding silver pyridinolates. Glycosides of halo-, hydroxymethyl- or methoxycarbonyl-nitrophenols as leaving groups gave virtually the same yields of transglycosylation products. A minor increase was achieved with nitrosalicylaldehyde as leaving group, whereas carboxy or amino derivatives gave very low or no yield of the transglycosylation product. Commercially available donors such as resorufinyl and 4-methylumbelliferyl β- d-galactopyranosides exhibited a lower transglycosylation potential than these novel pNP-Gal derivatives.

Investigation of acetyl migrations in furanosides

Standard reaction conditions for the desilylation of acetylated furanoside (riboside, arabinoside and xyloside) derivatives facilitate acyl migration. Conditions which favour intramolecular and intermolecular mechanisms have been identified with intermolecular transesterifications taking place under mild basic conditions when intramolecular orthoester formations are disfavoured. In acetyl ribosides, acyl migration could be prevented when desilylation was catalysed by cerium ammonium nitrate.

Synthesis of orthogonally protected biaryl amino acid derivatives

The efficient and direct synthesis of protected biaryl amino acids, including dityrosine (50% overall yield over 3 steps), by Negishi cross-coupling of the serine-derived organozinc reagent 4 with iodo- and di-iodobiaryls, is reported. An improved, although still not perfect, diiodination of 2,2'-biphenol has been achieved using NMe3BnICl2-ZnCl2. Protection of phenolic hydroxyl groups as acetates, rather than benzyl ethers, is required for efficient cross-coupling, and evidence for acetyl migration has been observed during debenzylation of a substituted 2-acetoxy-2'-benzyloxybiaryl. Aromatic C-I to C-Cl conversion has been detected as a minor reaction pathway in the palladium-catalyzed coupling of aryl iodide 3b with organozinc reagent 4.

Synthesis and Transformations of New Spiro-4-piperidines. Acetyl Migration in 1-Acetyl-1-Benzyl-4-Methyl-3,4-Dihydrospiro[(1H)quinoline-2,4-piperidines] Under Debenzylation Conditions

Synthesis of new dihydrospiro(quinoline-2,4'-piperidines) by a two-step synthetic route based on 4-piperidone imine reactivity is reported. An acetyl migration in 1-acetyl-1'-benzyl-4-methyl-3,4- dihydrospiro(quinoline-2,4'-piperidines) under debenzylation conditions (HCOONH4/Pd/C/MeOH) is found.

Lipase-catalysed preparation of acetates of 4-nitrophenyl β- d-xylopyranoside and their use in kinetic studies of acetyl migration

Di-O-acetates and mono-O-acetates of 4-nitrophenyl β- d-xylopyranoside were prepared by use of lipase PS-30. Polarity of organic solvents and reaction time affected the regioselectivity of the di-O-acetylation as well as the yields of monoacetates. The kinetics of acetyl groups migration in these derivatives was studied in aqueous media using HPLC. Migration of the acetyl group strongly depended on pH. The highest rate of acetyl migration was observed from O-2 to O-3 in both 2,4-di-O-acetate and 2-O-acetate. On the contrary, acetyl exchange between O-3 and O-4 in both directions was slower than between O-2 and O-3. The 2,3-di-O-acetate and 4-O-acetate showed to be the most stable towards acetyl migration. The 3,4-di-O-acetate and 4- O-acetate were dominant in the corresponding equilibration mixtures.

N-Phenylacetohydroxamic acid O-(tetra-O-acetyl)glucosideの酵素的O-脱Ac化における位置選択性と脱Ac化体の分子内Ac転位の速度論的解析

N-Phenylacetohydroxamic acid O-(tetra-O-acetyl)glucosideの酵素的O-脱Ac化における位置選択性と脱Ac化体の分子内Ac転位の速度論的解析

Methylation of dihydroquercetin acetates: synthesis of 5-O-methyldihydroquercetin.

The major products of methylation of dihydroquercetin (1, dhq) with diazomethane have been identified as 7-O-methyldhq (9), 7,3'-di-O-methyldhq (10), 7,4'-di-O-methyldhq (11), and 7,3',4'-tri-O-methyldhq (2). With dhq 3,7,3',4'-tetraacetate (6), dhq 3,5,3',4'-tetraacetate (5), dhq 3,3',4'-triacetate (7), dhq 7,3',4'-triacetate (8), and dhq 3-acetate (4) the same reaction affords mainly 5-O-methyldhq 3,7,3',4'-tetraacetate (15), 7-O-methyldhq 3,5,3',4'-tetraacetate (13), 7-O-methyldhq 3,3',4'-triacetate (14), 5-O-methyldhq 7,3',4'-triacetate (25), and 7-O-methyldhq 3-acetate (12), respectively. The methylation of 8 is accompanied by intermolecular acetyl migration from phenolic oxygen to the hydroxy group of the heterocyclic ring. 5-O-Methyldhq (28) is accessible by deacetylation of 25. 5,7-Di-O-methyldhq (29), four known methyl ethers, 13 new and three known methyl ether acetates of dhq, and six new isomers with 2,3-cis stereochemistry were spectroscopically identified.

Synthesis and antitumor activity of 2-( m-substituted-benzoyl)baccatin III analogs from taxinine

2- m-Azidobenzoyl and 2- m-chlorobenzoyl baccatin III analogs were prepared from taxinine, a major component in Japanese yew leaves. In this study, a novel acetyl migration from 13- to 4-hydroxyl group was observed. The antitumor activity of these compounds was evaluated.

Enhancement of CO Insertion into a Pd−C Bond in a Pd−Co Heterodinuclear Complex

A series of Pd-containing heterodinuclear methyl complexes, (dppe)(CH3)Pd−MLn (MLn = MoCp(CO)3, WCp(CO)3, Co(CO)4; dppe = 1,2-bis(diphenylphosphino)ethane), have been prepared by the metathetical reactions of Pd(CH3)(NO3)(dppe) with Na+[MLn]-, and the complexes were characterized by spectroscopic methods and/or X-ray structure analysis. Related Pt-containing dinuclear complexes were similarly prepared and characterized. The rate of CO insertion into a Pd−CH3 or Pt−CH3 bond was investigated using these complexes. The Pd−Co complex (dppe)(CH3)Pd−Co(CO)4 shows a high activity of CO insertion, giving (dppe)(CH3CO)Pd−Co(CO)4, and the initial rate is ca. 80 times higher than those of the analogous complex Pd(CH3)Cl(dppe). Whereas slow insertion of CO is observed in the Pt−Co complex (dppe)(CH3)Pt−Co(CO)4, no reaction takes place for Pt(CH3)Cl(dppe). It is revealed by using 13CO that CO in the Co(CO)4 fragment preferentially inserts into the Pd−CH3 bond over CO in the gas phase. The carbonyl insertion reaction in the Pd−Co heterodinuclear complex has been theoretically studied using B3LYP hybrid density functional theory to clarify its reaction mechanism and the electronic factors controlling the reaction. The calculations for a model complex, (H2PCH2CH2PH2)Pd(CH3)−Co(CO)4, have shown that the most favorable reaction path consists of methyl migration from the Pd to the Co atom, carbonyl insertion reaction on the Co atom, CO coordination to the Co atom, and acetyl migration from the Co atom to the Pd atom, which is in accord with the experimental results. The electron donation from the Pd d orbital to the bridging CO π* orbitals plays an important role in stabilizing the intermediates and transition states.

THE CHEMICAL STABILITY OF S-(2-ACYLTHIOETHYL) AND S-ACYLOXYMETHYL PROTECTED THYMIDYLYL-3′,5′-THYMIDINE PHOSPHOROMONOTHIOLATES AND THEIR DEACYLATION PRODUCTS IN AQUEOUS SOLUTION

The hydrolytic stability of the S-(2-acetylthioethyl) (1a,b), S-(2-pivaloyl- thioethyl) (2a,b), and S-acetyloxymethyl (3a,b) protected R P and S P phosphoromonothiolates of 3′,5′-TpT has been studied. Rather unexpectedly, an intramolecular hydroxide ion catalyzed acetyl migration from the protecting group to the nucleoside 3′- and 5′-hydroxy functions was found to compete with the intermolecular displacement of the AcSCH2CH2S- or AcOCH2S-ligand from the phosphorus atom of 1a,b and 3a,b, respectively. With the S-pivaloylthioethyl derivative 2a,b no such reaction took place. Additionally, the kinetics of the cleavage of the S-(2-mercaptoethyl) group from 4a,b, the products of enzymatic deacylation of 1a,b and 2a,b, were studied as a function of pH.

A long-range15N-NMR study of the oxazolidinone antibiotic zyvox® and the major thermal degradation products

The structures of the major thermal degradation products of linezolid (Zyvox®, PNU-100766) are reported. Following hydrolytic decarboxylation, the remaining oxazolidinone-derived skeleton of the antibiotic underwent a variety of acetyl migrations prior to deacetylation. Three of the degradation products are structural isomers. Structural characterization of the degradants was accomplished via the concerted analysis of 2D NMR, mass spectrometric, and infrared data. Direct and long-range 1H-15N heteronuclear shift correlation experiments at natural abundance were performed on linezolid as well as each of the isolated products of the degradation cascade. 15N chemical shifts for linezolid and each of the degradants, as well as the observed long-range 1H-15N coupling pathways are reported.

Esterase-catalysed regioselective 6-deacylation of hexopyranose per-acetates, acid-catalysed rearrangement to the 4-deprotected products and conversions of these into hexose 4- and 6-sulfates

The esterase from Rhodosporidium toruloides has been used to catalyse the hydrolysis of a series of per-acetylated α-D-hexopyranoses and α-D-hexopyranosides. Per-acetylated glucose 4, mannose 6, N-acetylgalactosamine 8, galactose 10, methyl α-D-glucoside 12, methyl α-D-mannoside 14 and methyl α-D-galactoside 16 have been selectively cleaved at the C-6 position by the esterase to give the 6-OH derivatives 5, 7, 9, 11, 13, 15 and 17. Acid-catalysed rearrangement of acetates 5, 7, 13, 15, 11, 17 and 9 with 4→6 acetyl migration gives the corresponding 4-deprotected derivatives 22–28, respectively. Hydrolyses of β-D-glucose pentaacetate 20 and α-D-lactose octaacetate 21 have been attempted, but no hydrolyses have been observed. 1,2,3,6-Tetraacylated α-D-hexopyranoses 3 and 22, derivatives of N-acetylglucosamine and glucose respectively, and 2,3,6-triacetylated α-D-hexopyranosides 24 and 25, derivatives of glucose and mannose, respectively, have been hydrolysed by the esterase to the corresponding 4,6-dihydroxy acetates 29, 18, 30 and 31. Acylation of methyl α-D-glucopyranoside 32 catalysed by the esterase provides the C-6 monoacetate 33 and the C-3 monoacetate 34 in 4 and 5% yield, respectively. The sodium salts of N-acetylglucosamine, glucose, N-acetylgalactosamine, galactose and mannose 6-sulfates 38–42, respectively, are prepared in two steps from the 6-deacetylated hexopyranoses 2, 5, 9, 11 and 7, respectively. The sodium salts of N-acetylglucosamine, glucose and mannose 4-sulfates 43–45, respectively, are prepared in two steps from the 4-deacetylated precursors 3, 22 and 26 which are obtained via acid catalysed 4→6 acyl migration of compounds 2, 5 and 7.

Selective acetylation reactions of hyaluronic acid benzyl ester derivative

The reaction of hyaluronic acid benzyl ester derivative ( 1) with trimethyl orthoacetate in the presence of an acid catalyst in N,N-dimethylformamide gave the expected 4,6-orthoester 2, along with its hydrolysed products the 6- O- ( 3) and the 4- O- ( 4) acetate hyaluronic acid benzyl esters as minor components. Acid hydrolysis of 2 followed by O-4→O-6 acetyl migration using t-butylamine afforded a mixture which contained the 6-acetate 3 as the major and the 4-acetate 4 as the minor compound. Synthesis of a mixture of 2′,3′,6- ( 6) and 2′,3′,4- ( 7) tri-acetates was achieved by peracetylation of 2 followed by treatment with aqueous acetic acid. Compound 1 on treatment with 2,2-dimethoxypropane in dimethyl sulfoxide in the presence of p-toluenesulfonic acid afforded the corresponding 4,6- O-isopropylidene derivative 8. The 2′,3′-di- O-acetate 10 was obtained from 8 by conventional acetylation followed by de-acetylation using trifluoroacetic acid. Acetylation of 1 with acetic anhydride in a mixture of N,N-dimethylformamide and pyridine gave the expected 2′,3′,4,6-tetraacetate derivative 11. In order to facilitate the NMR assignments of the acetate groups in 3– 11, the 2′,3′-diacetate-4,6-di(trideuterioacetate) 12 and the 2′,3′-di(trideuterioacetate)-4,6-diacetate 13 were prepared. The effect of substituents on conformational changes around the glycosidic linkages has been investigated.