Intramolecular Transesterification Reactions Research Articles

An exploratory study on the synthesis of heparin-like oligosaccharides by polycondensation

The synthesis of heparin oligosaccharide fragments by autocondensation of suitably protected D- glucosamine α1→4 L-iduronic acid disaccharide constructs containing both glycosyl- donor and glycosyl- acceptor functionalities has been explored. Trichloroacetimidate and n-pentenyl groups have been investigated for anomeric activation. The generation of building blocks equipped with a trichloroacetimidate function is seriously hampered by the presence of the free- OH glycosyl- acceptor group on the same molecule, which favors an intramolecular transesterification reaction. Using an n-pentenyl leaving group, the glycosylation promoter competes as a nucleophile with the OH glycosyl acceptor in the autocondensation process, giving rise to fast termination of the chain reaction, a low yield, and low degree of polymerization. It is concluded that, in this area, polycondensation can hardly compete with elaborate stepwise approaches as a result of the intrinsic low reactivity—both as a glycosyl donor and as glycosyl acceptor—of the D-glucosamine α1→4 L-iduronic acid building blocks.

Cleavage and Isomerization of RNA Phosphodiester Bonds: Nucleoside Phosphotriesters and Chimeric Ribo / 2-O-Methylribo Oligonucleotides as Tools for Mechanistic Studies

Phosphodiester bonds of RNA undergo in aqueous solution two intramolecular transesterification reactions: cleavage to a cyclic 27,3-phosphate and isomerization to a 2,5-phosphodiester. The reaction is initiated by a nucleophilic attack of the 2-hydroxy group on the phosphate, which results in formation of a pentacoordinated phosphorane species. This phosphorane intermediate may then decompose to either the cleavage or isomerization products. The reaction system is subject to several different type of catalysis, and under given conditions, different mechanisms may be concurrently utilized. The present review discusses the approaches where nucleoside 3-phosphotriesters have been used as a model for the neutral ionic form of phosphodiesters to elucidate the mechanistic details of the transesterification of RNA phosphodiester bonds. Transesterification of the phosphodiester bonds within oligonucleotidic substrates is also influenced by the molecular environment of the scissile bond. The secondary structure influences on the reactivity of RNA phosphodiester bonds either by retarding the rate of cleavage or enhancing it. These effects are discussed in the light of the mechanisms described above.

Two-Step Backbiting Reaction in the Ring-Opening Polymerization of γ-Acryloyloxy-ɛ-caprolactone Initiated with Aluminium Isopropoxide

γ-Acryloyloxyethyl-γ-butyrolactone is formed as a byproduct when the polymerization of γ-acryloyloxy-e-caprolactone is initiated with aluminium isopropoxide in toluene. The extent of this side reaction decreases with decreasing temperature and is dependent on whether the reaction is stopped as soon as monomer conversion is complete or not. A two-step backbiting mechanism is proposed for this intramolecular transesterification reaction.

Chemistry of gene silencing: the mechanism of NAD+-dependent deacetylation reactions.

The Sir2 enzyme family is responsible for a newly classified chemical reaction, NAD(+)-dependent protein deacetylation. New peptide substrates, the reaction mechanism, and the products of the acetyl transfer to NAD(+) are described for SIR2. The final products of SIR2 reactions are the deacetylated peptide and the 2' and 3' regioisomers of O-acetyl ADP ribose (AADPR), formed through an alpha-1'-acetyl ADP ribose intermediate and intramolecular transesterification reactions (2' --> 3'). The regioisomers, their anomeric forms, the interconversion rates, and the reaction equilibria were characterized by NMR, HPLC, 18O exchange, and MS methods. The mechanism of acetyl transfer to NAD(+) includes (1) ADP ribosylation of the peptide acyl oxygen to form a high-energy O-alkyl amidate intermediate, (2) attack of the 2'-OH group on the amidate to form a 1',2'-acyloxonium species, (3) hydrolysis to 2'-AADPR by the attack of water on the carbonyl carbon, and (4) an SIR2-independent transesterification equilibrating the 2'- and 3'-AADPRs. This mechanism is unprecedented in ADP-ribosyl transferase enzymology. The 2'- and 3'-AADPR products are candidate molecules for SIR2-initiated signaling pathways.

Lipase enhanced catalytic efficiency in lactonisation reactions

We studied an enantioselective lipase-catalysed transesterification reaction for the production of the statin lactone moiety. It is well known that the chiral cyclic structure of statins is very important for their pharmaceutical activity in the prevention and treatment of coronary artery diseases. We focused our attention on 3 R,5 R-6-(ethyl-2-phenyl)-4-hydroxytetrahydropyran-2-one ( 2); this was synthesised by employing an enantioselective lactonisation reaction catalysed by a commercial preparation of porcine pancreatic lipase (PPL) starting from a racemic mixture of syn-diol rac-1. Optimisation of the reaction conditions for the biocatalysed intramolecular transesterification reaction of the racemic diol 1 was carried out. It was seen that the maximal reaction rate could be greatly enhanced by the addition of solid matrices to the reaction medium.

Chondropsin D, a new 37-membered-ring macrolide lactam from the marine sponge Chondropsis species.

Chondropsin D (2), a new 37-membered-ring macrolide lactam, was isolated as a minor constituent of an aqueous extract of the marine sponge Chondropsis sp. This sponge sample had previously been the source of chondropsins A (1) and B, two novel polyketide-derived macrolides with potent cytotoxic activity. The structure of 2 was initially deduced from analysis of spectral data. This assignment was supported by the observation that chondropsin A (1), which contains a 35-membered macrocyclic ring, could be converted to chondropsin D (2) by a base-catalyzed intramolecular transesterification reaction. Rearrangement of the methylated derivative of chondropsin A (3) to the corresponding methylated analogue of chondropsin D (4) confirmed the structure of 2.

STRUCTURAL CHARACTERIZATION OF POLY(ϵ-CAPROLACTONE) AND POLY(ϵ-CAPROLACTONE-b-ISOBUTYLENE-b-ϵ-CAPROLACTONE) BLOCK COPOLYMERS BY MALDI-TOF MASS SPECTROMETRY

Poly(ϵ-caprolactone)(PC1) and PC1-polyisobutylene-PC1 (PC1-PIB-PC1) block copolymers were synthesized in anhydrous toluene by in situ conversion of 2-methyl-1-propanol (2M1P) and α,ω-dihydroxy PIB, respectively, to the corresponding aluminum alkoxide by reaction with a stoichiometric amount of triethylaluminum (TEA) followed by the addition of e-caprolactone. Structural characterization of 2M1P-initiated PCl by gel permeation chromatography (GPC) and matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) demonstrated the presence of cyclic oligomers, which are produced by intramolecular transesterification reactions that become significant at high monomer conversions. A minor fraction of chains bearing carboxylic acid termini was also observed in the MALDI-TOF mass spectrum; however, carboxylic acid chain ends could not be detected by 13C NMR analysis. Thus, the likely origin of the carboxylic acid termini is fragmentation of the initiator residue from the chain end during MALDI-TOF analysis. For PCl-PIB-PCl block copolymers, two different α,ω-telechelic PIB diols were used as macroinitiators, one derived from allyl and one from isopropenyl terminated PIB. Terminal olefins were converted to primary alcohols via regioselective hydroboration followed by alkaline hydrogen peroxide oxidation. After reaction with ϵ-caprolactone, formation of a block copolymer was evidenced by a shift of the polymer peak to lower elution volume in GPC analysis. Block copolymers possessed molecular weight distributions ≤1.4, and molecular weights of the PCl blocks calculated from GPC were in excellent agreement with those found using MALDI-TOF MS. Structural analysis indicated that the PCl end blocks were severed from the crude block copolymer during MS analysis, for both allyl- and isopropenyl-derived materials. For allyl-derived materials the PCl blocks were found to predominantly carry a C2 residue at the point of detachment of the PIB block; however, the isopropenyl-derived block copolymers showed a complex mixture of different residues suggesting a complex fragmentation mechanism during loss of the PIB block.

Novel block copolymers of 2-vinylpyridine and ɛ-caprolactone: Synthesis and characterization

Novel block copolymers based on 2-vinylpyridine (2VP) and ε-caprolactone (CL) have been synthesized via sequential anionic polymerization in tetrahydrofuran (THF). These block copolymers are expected to be promising pigment dispersing agents for TiO2 in e. g. polyester powder coatings. Initiation of CL by the living P2VP polymer occurred instantaneously and without side reactions. Intramolecular transesterification reactions were not observed either. However, part of the living chains was deactivated immediately after the addition of CL, which yielded bimodal molecular weight distributions. This could be attributed to strong aggregation of the alkoxide chain ends. Addition of LiCl to the polymerization mixture prevented aggregation and resulted in well-defined block copolymers. The block copolymers have been characterized with SEC, NMR and IR.

Mg2+-independent hairpin ribozyme catalysis in hydrated RNA films.

The hairpin ribozyme catalyzes RNA cleavage in partially hydrated RNA films in the absence of added divalent cations. This reaction exhibits the characteristics associated with the RNA cleavage reaction observed under standard conditions in solution. Catalysis is a site-specific intramolecular transesterification reaction, requires the 2'-hydroxyl group of substrate nucleotide A(-1), and generates 2',3'-cyclic phosphate and 5'-hydroxyl termini. Mutations in both ribozyme and substrate abolish catalysis in hydrated films. The reaction is accelerated by cations that may enhance binding, conformational stability, and catalytic activity, and is inhibited by Tb3+. The reaction has an apparent temperature optimum of 4 degrees C. At this temperature, cleavage is slow (k(obs): 2 d(-1)) and progressive, with accumulation of cleavage products to an extent of 40%. The use of synthetic RNAs, chelators, and analysis of all reaction components by inductively coupled plasma-optical spectrophotometry (ICPOES) effectively rules out the possibility of contaminating divalent metals in the reactions. Catalysis is minimal under conditions of extreme dehydration, indicating that the reaction requires hydration of RNA by atmospheric water. Our results provide a further caution for those studying the biochemical activity of ribozymes in vitro and in cells, as unanticipated catalysis could occur during RNA manipulation and lead to misinterpretation of data.

Relationship between internucleotide linkage geometry and the stability of RNA.

The inherent chemical instability of RNA under physiological conditions is primarily due to the spontaneous cleavage of phosphodiester linkages via intramolecular transesterification reactions. Although the protonation state of the nucleophilic 2'-hydroxyl group is a critical determinant of the rate of RNA cleavage, the precise geometry of the chemical groups that comprise each internucleotide linkage also has a significant impact on cleavage activity. Specifically, transesterification is expected to be proportional to the relative in-line character of the linkage. We have examined the rates of spontaneous cleavage of various RNAs for which the secondary and tertiary structures have previously been modeled using either NMR or X-ray crystallographic data. Rate constants determined for the spontaneous cleavage of different RNA linkages vary by almost 10,000-fold, most likely reflecting the contribution that secondary and tertiary structures make towards the overall chemical stability of RNA. Moreover, a correlation is observed between RNA cleavage rate and the relative in-line fitness of each internucleotide linkage. One linkage located within an ATP-binding RNA aptamer is predicted to adopt most closely the ideal conformation for in-line attack. This linkage has a rate constant for transesterification that is approximately 12-fold greater than is observed for an unconstrained linkage and was found to be the most labile among a total of 136 different sites examined. The implications of this relationship for the chemical stability of RNA and for the mechanisms of nucleases and ribozymes are discussed.

A Remarkable Rate-accelerating Metal Ion Effect on the Intramolecular Transesterification Reaction of a Phosphodiester in Acetonitrile

The intramolecular transesterification reaction of 2-hydroxypropyl 4-nitrophenyl phosphate is greatly accelerated (105–106 fold) by the addition of divalent metal ions such as Zn2+ and Cu2+ in MeCN without a base; the metal ion effect is quite sensitive to the content of H2O in MeCN.

A Remarkable Rate-accelerating Metal Ion Effect on the Intramolecular Transesterification Reaction of a Phosphodiester in Acetonitrile

Download options Please wait... Article information DOI https://doi.org/10.1039/A803986K Article type Paper Download Citation J. Chem. Res. (S), 1999, 106-107 BibTex EndNote MEDLINE ProCite ReferenceManager RefWorks RIS Permissions Request permissions A Remarkable Rate-accelerating Metal Ion Effect on the Intramolecular Transesterification Reaction of a Phosphodiester in Acetonitrile S. Kondo, K. Yoshida and Y. Yano, J. Chem. Res. (S), 1999, 106 DOI: 10.1039/A803986K 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. Search articles by author Shin-ichi Kondo Kitaro Yoshida Yumihiko Yano

Organotin(IV) Compounds as Intramolecular Transesterification Catalysts in Thermal Depolymerization of Poly(L-Lactic Acid) Oligomer to form LL-Lactide

ABSTRACT Mono-, di-, and tetraalkyl tin(IV) compounds were evaluated for the intramolecular transesterification reaction of the thermal depolymerization of poly(L-lactic acid) oligomer forming lactide by gas chromatography using a β-cyclodextrin stationary phase capillary column. The most active catalyst was found to be monobutyltin trichloride (BuSnC13) (8), which contains tinhalogen bonds, and the least effective was the coordinatively saturated monoorganotin derivative, monobutyltin tris(2-ethylhexanoate) (7). Cordination of the carbonyl group in the oligomer to the tin catalysts is an important factor influencing its activity.

Effect of Mixed Pendent Groups on the Solution and Catalytic Properties of Europium(III) Macrocyclic Complexes: Bifunctional and Monofunctional Amide and Alcohol Pendents in Septadentate or Octadentate Ligands

Five new Eu(III) macrocyclic complexes have been prepared and their solution and catalytic properties studied. The Eu(III) complexes with septadentate ligands TRED and NB-TRED dissociate rapidly at pH 7.4, 37 degrees C (TRED = 1,4,7-tris(hydroxyethyl)-1,4,7,10-tetraazacyclododecane, NB-TRED = 1-(nitrobenzyl)-4,7,10-tris(hydroxyethyl)-1,4,7,10-tetraazacyclododecane). Dissociation rates as determined in the presence and absence of strongly binding competing ligands suggest that under most conditions the Eu(III) complexes of ATHC, ABHC, and CNPHC are more kinetically inert to dissociation than is the Eu(III) complex containing all hydroxyethyl groups (ATHC = 1-(carbamoylmethyl)-4,7,10-tris(hydroxyethyl)-1,4,7,10-tetraazacyclododecane, ABHC = 1,7-bis(carbamoylmethyl)-4,10-bis(hydroxyethyl)-1,4,7,10-tetraazacyclododecane, CNPHC = 1-(1-carboxamido-3-(4-nitrophenyl)propyl)-4,7,10-tris(2-hydroxyethyl)-1,4,7,10-tetraazacyclododecane). Laser-induced luminescence excitation spectra of Eu(III) complexes of ABHC, ATHC, CNPHC, THED, and S-THP suggest that there is a single major species in solution at pH 6.3 and a second species that appears at more basic pH values (THED = 1,4,7,10-tetrakis(hydroxyethyl)-1,4,7,10-tetraazacyclododecane, S-THP = 1S,4S,7S,10S-tetrakis(2-hydroxypropyl)-1,4,7,10-tetraazacyclododecane). The species present at basic pH is proposed to be an alkoxide or hydroxide complex; pK(a) values as determined by potentiometric titrations are 7.5 and 8.1 for Eu(CNPHC)(3+) and Eu(ABHC)(3+), respectively. Eu(CNPHC)(3+), Eu(ATHC)(3+), and Eu(ABHC)(3+) promote transesterification of the hydroxypropyl ester of 4-nitrophenyl phosphate with pseudo-first-order rate constants at pH 7.3, 37 degrees C, and 1.00 mM complex of 1.4 x 10(-)(5), 9.3 x 10(-)(6), and 1.0 x 10(-)(6) s(-)(1), respectively. Both Eu(CNPHC)(3+)and Eu(ABHC)(3+) promote attack of an hydroxyethyl group of the macrocycle on bis(4-nitrophenyl) phosphate with pseudo-first-order rate constants at pH 7.3, 37 degrees C, and 1.00 mM complex of 1.5 x 10(-)(4) and 3.5 x 10(-)(5) s(-)(1), respectively. In general, an increase in the number of amide groups on the macrocycle of the Eu(III) complex decreases the rate of both intramolecular or intermolecular phosphate diester transesterification reactions.

Bulk polymerization of lactides initiated by aluminum isopropoxide. I. Mechanism and kinetics

AbstractCommercially available Al isopropoxide (Al(OiPr)3) has proved to be an efficient initiator for the bulk polymerization of lactide. The ring‐opening polymerization proceeds through a “coordination‐insertion” mechanism and the selective rupture of the acyl‐oxygen bond of the monomer. Polyester chains are selectively end‐capped with an aluminum alkoxide and an isopropoxy group. Therefore, substitution of Al tris(4‐penten‐1‐olate) for Al(OiPr)3 leads to the formation of macromonomers. In the temperature range from 110 to 150°C, polymerization is “living”, i.e. the molecular weight can be predicted by the initial monomer‐to‐Al molar ratio and the monomer conversion. The narrower polydispersity of poly(L,L‐lactide) compared to the amorphous poly(D,L‐lactide) (M̄w / M̄n 1.3 compared to 1.9, respectively), both prepared in the bulk, is thought to result from the restricted mobility of the crystallized isotactic polyester chains. When the temperature is increased up to 180°C, inter‐ and intramolecular transesterification reactions interfere with chain propagation.

Synthesis of SBC, SC and BC block copolymers based on polystyrene (S), polybutadiene (B) and a crystallizable poly(ε‐caprolactone) (C) block

AbstractThe sequential anionic polymerization of polystyrene‐block‐polybutadiene‐block‐poly(ε‐caprolactone) (SBC) triblock copolymers as well as polystyrene‐block‐poly(ε‐caprolactone) (SC) and polybutadiene‐block‐poly(ε‐caprolactone) (BC) diblock copolymers was achieved in benzene. To initiate the polymerization of the highly reactive ε‐caprolactone, the nucleophilicity of the carbanion has to be reduced. For this purpose 1,1‐diphenylethylene (DPE) was used. To avoid inter‐ and intramolecular transesterification reactions of the growing caprolactone block, the reaction time of this monomer in the block copolymers was strictly controlled. The reaction between polybutadienyl anions and DPE is too slow, and an incomplete reaction results in side reactions when ε‐caprolactone is added. An alternative method was developed, which consisted in the addition of a small quantity of styrene, after the polymerization of butadiene, to diminish the total reaction time and reduce the probability of chain transfer.