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The Reformatsky reaction of (3R,4R)-4-acetoxy-3-((1R)-1-{[tert-butyl(dimethyl)silyl]oxy}ethyl)­azetidin-2-one with ethyl 4-bromo-3-oxopentanoate gave product of replacement of the acetoxy group by C2-carbanion of the β-keto ester, which underwent retro-aza-Michael reaction with opening of the azetidinone ring with the formation of acyclic ethyl (2Z,4S,5R)-4-carbamoyl-5-{[tert-butyl(dimethyl)silyl]oxy}-2-pro­panoyl­hex-2-enoate. Treatment of the latter with di-tert-butyl dicarbonate afforded hex-3-enoate and dihydro­pyridin-6-one derivatives.

A resorcinarene-based hemicarcerand, which consists of two cavitands covalently linked to each other by four alkyl chains, allows structural expansion and contraction by demetalation and metalation of Cu(I) cations with a size change of approximately 12 A. This metal-mediated switching of the two states regulates the conformations of acetoxy group-terminated alkyl chains. A guest binding study reveals the encapsulation of heptyl to undecyl chains in metal-free and Cu(I)-coordinated capsules. The chemical shifts of the acetoxy groups of the bound guests are the same in the metal-free capsule, while those in the Cu(I)-coordinated one differ from each other. This indicates that the metal-free capsule regulates its size to the bound guests, while the bound guests adopt their conformations to the cavity of the Cu(I)-coordinated capsules. 1H NMR measurements and molecular mechanics calculations suggest that the bound guests have extended conformations in the metal-free capsule, while the Cu(I)-coordinated capsule forces the bound guests to adopt folded conformations. The presence of folded conformations is supported by the conformational study with structurally similar capsules and a nonsymmetric guest, allowing us to observe nuclear Overhauser effects stemming from the folded conformations of the guest in the cavity.

New norbornene-based functional multiblock copolymers containing ethylene–vinyl acetate/vinyl alcohol sequences are synthesized via the olefin cross-metathesis reaction of polynorbornene with poly(5-acetoxy-1-octenylene) followed by CC bond hydrogenation and acetoxy group deprotection. Macromolecular cross-metathesis, a recently developed type of interchange reaction, was carried out in the presence of Grubbs’ ruthenium catalysts and monitored by in situ1H NMR and ex situ13C NMR spectroscopy. This results in copolymer formation and its gradual randomization by segment reshuffling promoted by polymer-based Ru-carbenes. The kinetic study reveals that, despite the presence of bulky acetoxy substituents in polyoctenamer chains, Grubbs’ catalyst interacts with them more easily than with polynorbornene chains, which have cyclopentane rings in the backbone. The rate of the subsequent interchange reaction is controlled by the interaction of [Ru]-poly(5-acetoxy-1-octenylene) carbenes with norbornene units. It is found that the acetoxy groups markedly slow down the interaction of [Ru]-polynorbornene carbenes with the CC bonds in octenamer units. Since these carbenes are relatively unstable, they cause a noticeable decay of the reaction active centers. Our study demonstrates that the chain structure and, therefore, physico-chemical characteristics of multiblock copolymers can be tailored by adjusting the cross-metathesis conditions, such as the polymer concentration, polymer to catalyst ratio, and reaction time. Polymer-analogous reactions of hydrogenation and deacetylation transform octenamer units into ethylene–vinyl acetate/vinyl alcohol segments and thus open up more possibilities for tuning the thermal, gas barrier, and hydrophobic/hydrophilic properties of the synthesized norbornene-based multiblock copolymers.

Homogeneous polyimide (PI)/silica nanohybrid films were prepared using acetoxy group functionalized PI and silsesquiazane (SSQZ) as a silica precursor. During the heat treatment at 250 °C in a nitrogen atmosphere, the SSQZ was converted to silica. At the same time, the acetoxy groups of PI were converted into hydroxyl groups and formed covalent bonds with silica to make the resulting hybrid film homogeneous. FE-SEM and AFM analysis showed no evidence of macro-phase separation. As a result, the hybrid films exhibited improved thermal and mechanical properties, including 5% weight loss temperature, residual amount at 1,000 °C, coefficient of thermal expansion, and pencil hardness. The optical properties of the films also improved with showing a similar optical transmittance and lower yellow index.

Fifteen new analogues of (−)-cleistenolide (1) with aromatic ester groups at the C-6 position were designed and synthesized by multistep sequences. Steglich esterification of δ-pyrone 10 with selected aromatic acids (benzoic, cinnamic, and 4-substituted cinnamic acids) gave the corresponding 6-O-acyl derivatives 11–15. An original method was developed for the selective conversion of the primary benzyloxy group into the corresponding acetoxy function, giving five new bioisosteres (16–20) for biological testing. Finally, the dibenzyl derivative 11 was converted to the corresponding diacetate 2 using the AcBr/Zn(OTf)2 reagent system. For the transformation of compounds 12–15 into the corresponding 4,7-diacetates (3–6), in addition to Zn(OTf)2, it was necessary to use FeCl3 as a co-catalyst. The cleistenolide analogues thus obtained were tested for their in vitro antitumour activity The majority of compounds showed higher potency compared to lead 1 toward five of six investigated human tumour cell lines, but were almost completely inactive in the culture of normal foetal fibroblasts (MRC-5). The most potent antiproliferative activity was shown by 4,7-di-O-benzyl derivatives 13 and 14, with IC50 values of 0.04 (HeLa) and 0.09 μM (Jurkat), respectively. Preliminary SAR analysis revealed some of the structural features important for the activity of this class of compounds. These are: the presence of unsubstituted cinnamate function at the C-6 position and the presence of an acetoxy group at the C-4 position.

In this study, a series of variously substituted 2,3-dihydroquinolin-4-imines (DQIs) were synthesized from N-substituted propargylanilines by copper(I)-catalyzed annulation. The approach adopted in this study under mild, effective conditions exhibited broad substrate tolerance, particularly for functional groups substituted on anilines. Most of the DQI derivatives synthesized under optimal conditions were obtained in good isolated yields of 63-88 %. 2,3-Dihydroquinolinimine thus obtained was easily converted to important structures like 2,3-dihydroquinolone and tetrahydrobenzodiazepin-5-one, confirming the importance of this strategy in constructing various heterocycles. Surprisingly, 2,3-dihydroquinolinimines thus obtained exhibited bright fluorescence with quantum yields up to 66 %. The density functional theory (DFT) and time-dependent DFT (TD-DFT) calculations were performed for understanding the excited-state nature of DQI system. Accordingly, a tailored DQI derivative bearing methoxy group at C-6 position and acetoxy group at C-7 position was designed and synthesized to give emission at 559 nm with redshift compared to the 7-methoxy substituted DQI. A detailed study of DQI structures with their photophysical properties was performed with five control molecules and consequently demonstrated the uniqueness of the chemical structures of DQIs.

A novel retro-ene reaction via a [4.4.3]propellane intermediate containing a quaternary ammonium linkage was developed. The feature of this acetic anhydride mediated rearrangement includes the elimination of an acetoxy group at the C14 position and subsequent intramolecular nucleophilic addition of a nitrogen functional group to form an isolable ammonium salt intermediate. We clarified the reaction mechanism utilizing the deuterated derivative.

13C NMR spectroscopic studies were performed for carbonyl compounds having a hydroxyl group, a carboalkoxy group, an acetoxy group, or a carboxyl group in various solvents with different polarities for observation of their behaviors of 13C NMR chemical shifts of carbonyl carbons in solutions. It was found that the chemical shifts of the carbonyl carbons in 13C NMR have good correlation with the empirical parameter for solvent polarities, ETN, depending on the structures. Inter- or intramolecular hydrogen bonding and dipolar-dipolar interactions appear to play a key role in this observation.

Chemoenzymatic synthesis and modification of well-defined macrolactonic sophorolipid (SLML) analogues via a series of successive regioselective de-esterification/transesterification reactions is investigated. Of the lipases screened, Candida antartica lipase- B (Novozyme-435) successfully deacylated the C-6′ acetoxy group of natural and peracylated SLMLs. Subsequent transesterification with acylating agents (esters of fatty acids) was successful only with the C-6′ deacetylated natural SLML providing an avenue to well-defined analogues of varying amphilicity. The macrolactonic motif was essential for enzymatic recognition of the sophorose rings of these complex glycolipids. In the absence of the lactonic motif, the peracylated sophorose rings are not deacylated, rather the carboxyl end of the non-lactonic forms that was preferentially transesterified. All macrolactonic derivatives were characterized by IR, 1H, 13C, 1H-1H and 1H-13C NMR spectroscopy, as well as HRMS where applicable.

The development of a cyclization reaction to access amino-1,3-oxazines under mild conditions is described. The synthesis was achieved using dehydrating reagents, such as phosphorus pentoxide and Burgess reagent. In particular, the cyclization with Burgess reagent proceeded under mild conditions and tolerated potentially labile functional groups, such as the acetoxy group, and therefore can be used to synthesize β-secretase (BACE1) inhibitors with a variety of amino-1,3-oxazine warheads.

Starting from (±)-3-acetoxyglutarimide, diastereoselective formal synthesis of indole alkaloids (±)-eburnamonine, (±)-eburnaminol, and (±)-vindeburnol have been demonstrated via a common intermediate (±)-1-hydroxy-12-tosyl-2,3,6,7,12,12b-hexahydroindolo[2,3- a ]quinolizin-4(1 H )-one in very good overall yields. The acetoxy group from (±)-3-acetoxyglutarimide was first used to induce the diastereoselectivity and also as a latent source of ketone carbonyl group. The ste­reo­selective eliminations, reductions, and intramolecular cyclizations were the involved key steps.

Reaction of ethyl 2-bromomethyl-5-(1,2,3-thiadiazol-4-yl)furan-3-carboxylate with nucleophiles of different nature was studied. It is shown that substitution of bromine with acetoxy group takes place under the action of sodium acetate in the acetic acid. Stronger bases, like phenolates, cause considerable decomposition of the labile furylthiadiazole fragment Decomposition can be avoided only when this reaction is carried out in the presence of a phase transfer catalyst under the conditions of the ion pair extraction,. In the reaction with sodium N,N-diethyl dithiocarbaminate the corresponding thioester is formed. Butanethiol and thiophenol are alkylated as potassium thiolates. In the last case S-alkylation proceeds exclusively. Reaction with excess 2-aminoethanol permits to prepare secondary amine, and the reactions with pyrrolidine, piperidine, and morpholine give the corresponding tertiary amines. Phosphorylation with triethyl phosphite under the conditions of Arbuzov reaction leads to the corresponding diethyl phosphonate. In all these transformations furylthiadiazole fragment is retained.

A catalytic enantioselective synthesis of the hexahydropyrrolo[3,2-c]quinoline core structure found in the Martinella alkaloids, martinelline and martinellic acid, is described. The synthesis is completed without the use of any chiral building blocks or chiral auxiliaries. The key steps in our synthesis constituted a Sp2-Sp3 Suzuki-Miyaura cross-coupling reaction between a triflate and an N-protected β-aminoethyl boron species to provide a 1,2-dihydroquinoline carrying a N-protected β-aminoethyl group in the 3-position, Sharpless asymmetric dihydroxylation of the 1,2-dihydroquinoline derived from the Suzuki-Miyaura cross-coupling reaction, and an acid promoted intramolecular diastereoselective amido cyclisation with the aid of a neighbouring acetoxy group to provide the tricyclic architecture of martinelline and martinellic acid. Our catalytic enantioselective synthesis provided the hexahydropyrrolo[3,2-c]quinoline core structure of the Martinella alkaloids in 75 % ee.

tert-Butyl esters are demonstrated to function as chain transfer agents (CTAs) in the cationic copolymerization of vinyl ether (VE) and oxirane via concurrent vinyl-addition and ring-opening mechanisms. In the copolymerization of isopropyl VE and isobutylene oxide (IBO), the IBO-derived propagating species reacts with tert-butyl acetate to generate a copolymer chain with an acetoxy group at the ω-end. This reaction liberates a tert-butyl cation; hence, a polymer chain with a tert-butyl group at the α-end is subsequently generated. Other tert-butyl esters also function as CTAs, and the substituent attached to the carbonyl group affects the chain transfer efficiency. In addition, ethyl acetate does not function as a CTA, which suggests the importance of the liberation of a tert-butyl cation for the chain transfer process. Chain transfer reactions by tert-butyl esters potentially occur reversibly through the reaction of the propagating cation with the ester group at the ω-end of another chain.

A new series of furofuran lignans containing catechol moiety were prepared from the reactions between lignans and a variety of phenolics. All 22 products obtained were evaluated against three different α-glucosidases (maltase, sucrase and Baker’s yeast glucosidase) and DPPH radical. Of furofuran lignans evaluated, β-14, having two catechol moieties and one acetoxy group, was the most potent inhibitor against Baker’s yeast, maltase, and sucrase with IC50 values of 5.3, 25.7, and 12.9 µM, respectively. Of interest, its inhibitory potency toward Baker’s yeast was 28 times greater than standard drug, acarbose and its DPPH radical scavenging (SC50 11.2 µM) was 130 times higher than commercial antioxidant BHT. Subsequent investigation on mechanism underlying the inhibitory effect of β-14 revealed that it blocked Baker’s yeast and sucrase functions by mixed-type inhibition while it exerted non-competitive inhibition toward maltase. Molecular dynamics simulation of the most potent furofuran lignans (4, α-8b, α-14, and β-14) with the homology rat intestinal maltase at the binding site revealed that the hydrogen bond interactions from catechol, acetoxy, and quinone moieties of furofuran lignans were the key interaction to bind tightly to α-glucosidase. The results indicated that β-14 possessed promising antidiabetic activity through simultaneously inhibiting α-glucosidases and free radicals.

We report herein the first examples of asymmetric oxidation of enol ether and ester substrates using iminium salt organocatalysis, affording moderate to excellent enantioselectivities of up to 98% ee for tetralone-derived substrates in the α-hydroxyketone products. A comprehensive density functional theory study was undertaken to interpret the competing diastereoisomeric transition states in this example in order to identify the origins of enantioselectivity. The calculations, performed at the B3LYP/6-31G(D) level of theory, gave good agreement with the experimental results, in terms of the magnitude of the effects under the specified reaction conditions, and in terms of the preferential formation of the ( R)-enantiomer. Just one of the 30 characterized transition states dominates the enantioselectivity, which is attributed to the adoption of an orientation relative to stereochemical features of the chiral controlling element that combines a CH-π interaction between a CH2 group in the substrate and one of the aromatic rings of the biaryl section of the chiral auxiliary with a good alignment of the acetoxy group with the other biaryl ring, and places the smallest substituent on the alkene (a hydrogen atom) in the most sterically hindered position.

The oxidative deamination of N-nitroso N-acetylneuraminic acid (NeuAc) derivatives is a useful reaction for the formation of 5-desamino-5-hydroxy NeuAc derivatives and their stereoisomers. We demonstrated previously that replacement of the classical nucleophile in these reactions, acetic acid, by phenols resulted in a novel double displacement process with substitution of the acetoxy group at the 4-position taking place in addition to that of the 5-acetamido group, for which we postulated a mechanism centered on the formation of a highly reactive vinyl diazonium ion. We now extend these studies to encompass the use of hydroxylamine-based systems and weakly basic amines as nucleophile. We find that the nature of the product depends significantly on the pKa of the nucleophile, with the more acidic species typically affording only substitution at the 5-position, while the less acidic species give mixtures of elimination products and disubstitution products. The use of aniline as nucleophile is of particular note as it affords a novel aziridine spanning positions 4- and 5- of the neuraminic acid skeleton.

Testosterone (T) plays a crucial role in prostate growth. In androgen-dependent tissues T is reduced to dihydrotestosterone (DHT) because of the presence of the 5α-reductase enzyme. This androgen is more active than T, since it has a higher affinity for the androgen receptor (AR). When this mechanism is altered, androgen-dependent diseases, including prostate cancer, could result. The aim of this study was to synthesize several 16-dehydropregnenolone acetate derivatives containing a triazole ring at C-21 and a linear or alicyclic ester moiety at C-3 of the steroidal skeleton. These steroids were designed as potential inhibitors of the activity of both types (1 and 2) of 5α-reductase. The cytotoxic activity of these compounds was also evaluated on a panel of PC-3, MCF7, and SK-LU-1 human cancer cell lines. The results from this study showed that with the exception of steroids 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-propionate and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-pentanoate, the compounds exhibit a lower inhibitory activity for both isoenzymes of 5α-reductase than finasteride. Furthermore the 3β-hydroxy-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-20-one and 20-oxo-21-(1H-1,2,4-triazole-1-yl)pregna-5,16-dien-3β-yl-acetate derivatives display 80% cytotoxic activity on the SK-LU-1 cell line. These results also indicated that the triazole derivatives, which have a hydroxyl or acetoxy group at C-3, could have an anticancer effect, whereas the derivatives with a alicyclic ester group at C-3 do not show biological activity.

Methyl 5-acetyl-2-furoate has been prepared via oxidation of 5-(1-hydroxyethyl)-2-furoate with the Jones reagent. In turn, the starting compound has been synthesized via sequential chloroethylation of ethyl 2-furoate, substitution of chlorine with acetoxy group, and methanolysis of the acetate in presence of sodium methylate. The vinylog 2-furoate has been obtained as the major product via acetylation of ethyl 3-(2-furyl)-acrylate with acetic anhydride in the presence of magnesium perchlorate.

A pedagogically useful discovery-based undergraduate organic chemistry lab experiment probing the chemo- and diastereoselectivity in the NaBH4 reduction of two chiral ketoesters (benzoin acetate and benzoin benzoate) has been developed. This experiment complements a previously described and highly popular discovery-based experiment that probes the stereoselectivity in the NaBH4 reduction of the chiral ketone (±)-benzoin. Using reactions described in standard textbooks, students convert (±)-benzoin to the ketoester derivatives (±)-benzoin acetate and (±)-benzoin benzoate. In contrast to benzoin that has a single reducible ketone functional group, the ketoester derivatives have two reducible functional groups. In addition, the structural modifications made to the hydroxyl group of the benzoin molecule lead to an increase in the effective steric bulk of the OH group of benzoin, affording a larger acetoxy group and an even larger benzoxy group. Using NMR spectroscopy, students probe not only the chemoselectiv...

Twenty acyclic monoterpenes with different functional groups (acetoxy, hydroxyl, carbonyl and carboxyl) bearing a variable number of carbon double bonds were assayed as repellent and larvicidal agents against the West Nile vector Culex pipiens. Seven of them were derivatives that were synthesized through either hydrogenation or oxidation procedures. All repellent compounds were tested at the dose of 1mgcm(-2) and only neral and geranial were also tested at a 4-fold lower dose (0.25mgcm(-2)). Repellency results revealed that geranial, neral, nerol, citronellol, geranyl acetate and three more derivatives dihydrolinalool (3), dihydrocitronellol (5) and dihydrocitronellyl acetate (6) resulted in no landings. Based on the LC50 values the derivative dihydrocitronellyl acetate (6) was the most active of all, resulting in an LC50 value of 17.9mgL(-1). Linalyl acetate, citronellyl acetate, neryl acetate, geranyl acetate, dihydrocitronellol (5), dihydrocitronellal (7), citronellol, dihydrolinalyl acetate (2), citronellic acid and tetrahydrolinalyl acetate (1) were also toxic with LC50 values ranging from 23 to 45mgL(-1). Factors modulating toxicity have been identified, thus providing information on structural requirements for the selected acyclic monoterpenes. The acetoxy group enhanced toxicity, without being significantly affected by the unsaturation degree. Within esters, reduction of the vinyl group appears to decrease potency. Presence of a hydroxyl or carbonyl group resulted in increased activity but only in correlation to saturation degree. Branched alcohols proved ineffective compared to the corresponding linear isomers. Finally, as it concerns acids, data do not allow generalizations or correlations to be made.

The living cationic polymerization of 6-tert-butoxy-2-vinylnaphthalene (tBOVN), a vinylnaphthalene derivative with an electron-donating group, was achieved with a TiCl4/SnCl4 combined initiating system in the presence of ethyl acetate as an added base at –30 °C. The absence of side reactions at low temperature was confirmed by 1H NMR analysis of the resulting polymer. In contrast to this controlled reaction at –30 °C, reactions performed at higher temperature, such as 0 °C, frequently involved unwanted intramolecular or intermolecular Friedel–Crafts reactions of naphthalene rings due to the high electron density of these rings. The cationic polymerization of 6-acetoxy-2-vinylnaphthalene, a derivative with an acetoxy group, was also controlled under similar conditions, but chain transfer reactions were not completely suppressed during the polymerization of 2-vinylnaphthalene. The glass transition temperature (Tg) of the obtained poly(tBOVN) was 157 °C, a value higher by 94 °C than that of the corresponding styrene derivative. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 4828–4834

RATIONALE Dimeric sesquiterpene lactones (DSLs) exhibit more 'biological friendly' and 'drug-like' molecular features than their monomers. Identification of DSLs is important to uncover potential lead compounds for the development of new anti-inflammatory and anticancer drugs. METHODS High-performance liquid chromatography coupled with electrospray mass spectrometry (HPLC/ESI-MS(n) ) in positive-ion mode was developed to analyze structurally related groups of DSLs in the species of Inula japonica Thunb. The aerial part of I. japonica was also analyzed by using HPLC-diode-array detection (DAD)/ESI-MS(n) for the purpose of method validation. RESULTS In positive-ion mode, a wealth of precursor molecular ions and product ions was detected for 24 DSL standards by MS(n) analysis under collision-induced dissociation. Retro-Diels-Alder (RDA) cleavage of the guaiane-type SL, neutral losses of acetoxy group, CO2 and water during the MS(n) process yielded characteristic product ions. The chemical constituents of the crude extract of I. japonica have also been analyzed by the developed method. CONCLUSIONS The results indicated that the developed analytical method could be employed as a rapid, effective technique for structural characterizations of DSL-type constituents in I. japonica. This study may also arouse interest for further structural analysis of other DSL-containing type herbal medicines.

Electrospray ionisation mass spectrometry was used to investigate the mechanism of inhibition of porcine pancreatic elastase (PPE) by two cephalosporins, L-658758 [1-[[3-(acetoxymethyl)-7α-metyoxy-8-oxo-5-thia-1-azabicyclo[4.2.0.]oct-2-en-2-yl]carbonyl]proline S,S dioxide], and L-647957 [1-[[3-(acetoxymethyl)-7α-chloro-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-2-yl]carboxylic t butyl ester]S,S dioxide]. The mass shifts, observed as compared with native PPE, upon incubation with the inhibitors were consistent with the formation of an acyl enzyme complex followed by expulsion of the acetoxy group from the 3′-methylene position of the cephalosporin inhibitors. In the case of L-647957 the mass shifts also indicated loss of HCl. In contrast for L-658758, no evidence was accrued for loss of methanol, consistent with previous kinetic studies on human leukocyte elastase.

A series of peracetylated O -aryl α,β- d -ribofuranosides have been synthesized and an efficient biocatalytic methodology has been developed for the separation of their anomers which was otherwise almost impossible by column chromatographic or other techniques. The incubation of 2,3,5-tri- O -acetyl-1- O -aryl-α,β- d -ribofuranoside with Lipozyme® TL IM immobilized on silica led to the selective deacetylation of only one acetoxy group, viz the C-5′- O -acetoxy group of the α-anomer over the other acetoxy groups derived from the two secondary hydroxyl groups present in the molecule and also over three acetoxy groups (derived from one primary and two secondary hydroxyls of the β-anomer). This methodology led to the easy synthesis of both, α- and β-anomers of O -aryl d -ribofuranosides. All the arylribofuranosides were screened for inhibition of Src kinase. 1- O -(3-Methoxyphenyl)-β- d -ribofuranoside exhibited the highest activity for inhibition of Src kinase (IC 50 = 95.0 μM).

A new synthetic approach to (+)-batzellaside B from naturally abundant L-pyroglutamic acid is presented in this article. The key synthetic step involves Sharpless asymmetric dihydroxylation of an olefinic substrate functionalized with an acetoxy group to introduce two chiral centres diastereoselectively into the structure. Heterocyclic hemiaminal 4, which could be converted from the resulting product, was found to provide stereospecific access to enantiomerically enriched allylated intermediate, offering better prospects for the total synthesis of this natural product.

The opening of the epoxide bridge in N-substituted 2,3,7,7a-tetrahydro-3a,6-epoxyisoindol-1-ones by the action of BF3⋅Et2O in acetic anhydride at 25°C over 1 h proceeds through an SN1 mechanism. The allylic type cation formed in the first step is stabilized by the addition of an acetoxy group at C-5 in the isoindole system to give a mixture of cis and trans isomers of 5,6-diacetoxy-2,3,5,6,7,7a-hexa-hydroisoindol-1-ones, which are aromatized under these conditions over 24 h to give 2,3-dihydro-1H-isoindol-1-ones.

Geometry optimizations at the B3LYP level of density functional theory (DFT) are reported for the 4 H 5 and 5 H 4 conformations of four glycals: 3,4-di- O -acetyl-1,5-anhydro-2-deoxy- d - erythro -pent-1-enitol (3,4-di- O -acetyl- d -arabinal), its d - threo isomer (3,4-di- O -acetyl- d -xylal), 3,4-di- O -acetyl-1,5-anhydro-2,6-dideoxy- d - arabino -hex-1-enitol (3,4-di- O -acetyl- d -rhamnal), and its d - lyxo isomer (3,4-di- O -acetyl- d -fucal). The Gibbs free energies, relative Gibbs free energies and geometry parameters are presented for all the optimized structures. Conformational analysis of both the acetoxy groups and 1,2-unsaturated pyranoid ring is performed. It is demonstrated that the acetoxy group is planar and adopts two conformations with regard to the Ac-O bond rotations, one of which is strongly preferred. One of the hydrogen atoms of the methyl group is always oriented synperiplanarly whereas the remaining two anticlinally with respect to the carbonyl oxygen. With regard to the AcO–R bond rotations some of the orientations are forbidden. The calculations indicate that 3,4-di- O -acetyl- d -arabinal adopts mainly the 4 H 5 conformation, whereas 3,4-di- O -acetyl- d -xylal prefers the 5 H 4 form, owing to the vinylogous anomeric effect (VAE). Competition between the VAE and quasi 1,3-diaxial interactions means that both 3,4-di- O -acetyl- d -rhamnal and 3,4-di- O -acetyl- d -fucal remain in the 4 H 5 ⇄ 5 H 4 conformational equilibrium, shifted in the 4 H 5 direction. It seems that the orientation of the 4-OAc group influences the quasi 1,3-diaxial interactions between 3-OAc and 5-CH 3 groups. Theoretical results are compared with assignments based on 1 H NMR studies.

An indium triiodide-catalyzed substitution of the acetoxy group in alkyl acetates with thiosilanes provides access to a variety of thioethers. The method is efficient for a wide scope of acetates such as primary alkyl, secondary alkyl, tertiary alkyl, allylic, benzylic, and propargylic acetates.

The manganese(III) acetate-mediated free radical cyclization of diarylmethylenecyclopropa[b]naphthalenes with nucleophiles such as carboxylic acid and sulfonic acid provides an efficient method for the synthesis of 1,2-benzanthracenes in moderate to good yields under mild conditions. In addition, after several steps of simple and routine operations, the obtained 1,2-benzanthracenes bearing an acetoxy group could be easily converted to structurally more sophisticated 1,2-benzanthracene derivatives, which are not easily accessible yet potentially useful candidates for materials science.

Treatment of alkylbenzenes with (diacetoxyiodo)benzene in the presence of catalytic amounts of p-toluenesulfonamide or p-nitrobenzenesulfonamide, and molecular iodine in 1,2-dichloroethane at 60 °C gave the corresponding (α-acetoxy)alkylbenzenes in good to moderate yields. The present reaction is a simple method for the introduction of an acetoxy group to the benzylic position of alkylbenzenes.

Benzyl acetate reacted with allyltrimethylsilane to give an allylation product in the presence of a catalytic amount of the (cyclooctadiene)rhodium(I) chloride dimer ([Rh(cod)Cl] 2 }, sodium tetrakis[3,5-bis(trifluoromethyl)phenyl]borate (NaBARF), and triphenyl phosphite [P(OPh) 3 ] in refluxing 1,2-dichloroethane. Primary, secondary and tertiary benzyl acetates could be used for the reaction. Moreover, allylation of gem-benzyl acetate was possible with [Rh(cod)Cl] 2 , NaBARF, and P(OPh) 3 . Monoallylation and diallylation of gem-benzyl acetate could be controlled by altering the reaction conditions. Cationic rhodium species generated in situ act as a Lewis acid catalyst to give a benzyl carbocation by elimination of the acetoxy group from the benzylic carbon.

Replacement of the acetoxy group in 3-methylbenzoylaminomethyl acetate with N- and S-nucleophiles generated from amines and thio compounds using sodium hydride gives the corresponding N-aminomethyl- and N-thiomethylbenzamides.

Having developed the one-pot triacetylation of indolin-3-ones, we have now devised a simple two-step reaction sequences to produce di- and mono-acetylated indoles from indolin-2-ones. The indolin-2-ones were first subjected to acetylation in the presence of acetic anhydride and a catalytic amount of N,N-dimethylaminopyridine to give 2-acetoxy-1,3-diacetylindoles. Subsequently, an enzyme-assisted deacetylation resulted in the chemoselective deprotection of the acetoxy group to produce 1,3-diacetyl-2-hydroxyindoles. However, a chemical deacetylation of 2-acetoxy-1,3-diacetylinoles under mild basic or acidic conditions resulted in the formation of 3-acetyl-2-hydroxyindoles.

Reactions of acylated Baylis–Hillman adducts bearing nitrile, ester, or ketone groups with C6F5-substituted silicon reagents MenSi(C6F5)4–n (n = 1–3) have been studied. The reactions are initiated by Bu4NOAc (5 mol-%) in MeCN or DMF under mild conditions and afford products of allylic substitution of the acetoxy group by the C6F5 carbanion in good yields. Predominant or exclusive formation of one geometrical isomer was observed in all cases (Z for nitriles, E for esters and ketones). For substrates containing carbonyl groups, nucleophilic attack of the C6F5 carbanion chemoselectively occurred at the C=C bond. Reactions of acylated Baylis–Hillman adducts with Me3SiCF3 were found to be inefficient, as the CF3 carbanion had the propensity to attack the C=O bond of substrates with ester or ketone substituents.

The synthesis of sulfines (thione oxides) (2, 10 and 17) derived from three chiral dithio esters (1, 8 and 16) bearing a hydrogen at the α-carbon atom is described. The sulfine bearing an amido group at C-α (2), does not racemize and proved to be stable over a long period. When C-α in the sulfine (10) bears an acetoxy group the optical activity remained unchanged for a period of two months; after longer storage a rearrangement to a mixture of dithioperoxy ester 12 and S-methyl ester 11 took place. With an alkyl group at C-α, the sulfine 17 undergoes a fast racemization and rearranges slowly to a mixture of S-ethyl ester 14, dithioperoxy ester 18 and S-vinyl thiosulfinate 19.

By the reaction of 3-(3′-acetoxyoctyl)-2-(6′-carboxyhexyl)-2-cyclopenten-1-one, the acetoxy derivative of Prostaglandin E1 - 237 (PGE1 - 237), with N-bromosuccinimide in carbon tetrachloride, followed by treatment of the reaction product with silver acetate in acetic acid, an acetoxy group was introduced at the allyl position of the ring. After hydrolysis of both acetoxy groups, 2-(6′-carboxyhexyl)-4-hydroxy-3-(3′-hydroxyoctyl)-2-cyclopenten-1-one was obtained. In an attempt to convert the latter into 2-(6′-carboxyhexyl)-4-hydroxy-3-(3′-hydroxyoctyl)-1-cyclopentanone (racemic dihydro-PGE1), hydrogenation with a 5 % rhodium on carbon catalyst was carried out. Both reduction of the double bond in the ring and hydrogenolysis of the hydroxy group attached to the ring occurred, leading to 2-(6′-carboxyhexyl)-3-(3′-hydroxyoctyl)-1-cyclo-pentanone. However, racemic dihydro-PGE1 was also obtained in low yield. It showed some biological activity on blood-platelet aggregation.

Cephalosporins remain one of the most important classes of antibiotics. A useful site for derivatization involves generation of and chemistry at the 3'-hydroxymethyl position. While 3'-acetoxymethyl-substituted cephalosporins are readily available, deacetylation to access the free 3'-hydroxymethyl group is problematic when the carboxylic acid is protected as an ester. Herein we report that this important transformation has been efficiently accomplished using Candida antarctica lipase B. Although this transformation is difficult to carry out using chemical methods, the enzymatic deacetylation has been successful on gram scale, when the cephalosporin is protected as either the benzhydryl or tert-butyl esters and on the corresponding sulfoxide and sulfone of the tert-butyl ester.

The electrochemical bromination of 3,4.6-tri-O-acetyl-D-glucal (1) has been investigated in dimethyl sulfoxide (DMSO) by cyclic voltammetry and preparative-scale electrolyses. In this solvent, the bromination involves a bromine-DMSO complex of the type [DMSO-Br](+) Br(-) whose reactivity towards 1 was clearly evidenced by cyclic voltammetry. Importantly, only the monobrominated glucose and mannose derivatives were obtained from electrolyses. This specific behavior was attributed to the nucleophilicity of DMSO that may react with the oxocarbenium intermediate preventing thus a possible second bromination of the transient species. The gluco/manno ratio, roughly equal to 30/70, indicated an electrophilic attack by [DMSO-Br](+) Br(-) preferentially from the beta side of the starting glycal for steric reasons. The treatment of the crude product obtained after the end of the electrolyses with acetic anhydride allowed the preparation of derivatives in which the anomeric carbon bears an acetoxy group. Based on both the cyclic voltammetry experiments and preparative-scale electrolyses, a mechanism is proposed for the bromination of peracetylated D-glucal in DMSO. These new and original results are of high interest in carbohydrate chemistry and especially for the preparation of new valuable oligosaccharides. (C) 2009 Elsevier Ltd. All rights reserved.

The structure and dynamics of the Dess-Martin periodinane, a I(V) iodobenzene compound widely used in organic synthesis as a mild oxidant, were studied by a combined (17)O NMR and DFT calculations approach. The results show that a degenerate [1,3] sigmatropic shift of iodine between the two oxygen atoms of each of the three acetoxy groups occurs in solution. The energy barrier of this process depends on the position of the acetoxy group with respect to the iodoxolone ring and is much lower than the energy barrier observed for similar I(III) compounds.

The acetoxy-functionalized bis(imidazolyl)borate [B(ImN-Me)2(OC( O)Me)Me]− (=LOAc) is synthesized by the reaction of the alkoxy precursor [B(ImN-Me)2(OPri)Me]− (=LOiPr) with acetic acid. In the presence of weak Bronstead acid, migration of nickel-bound acetate anion to the boron center giving LOAc occurs. The boron–acetoxy linkage survives upon the treatment of the nickel complexes with OH−, although the acetoxy group on LOAc does not coordinate to the nickel center.

Some photochromic diarylethenes having polar substituents were synthesized, and their photochromic behavior was examined. They exhibited photochromism with the similar photoreactivity in a non-polar solvent. However, the photocyclization quantum yield of dithienylperfluorocyclopentene having diethylamino group was found to decrease in polar solvents. The yield in acetonitrile was estimated to be 60 times smaller than that in hexane. The yields determined in various solvents were found to be correlated with the solvent polarity parameter ET(30). Such an effect was not observed in dithienylfluorocyclopentenes bearing methoxy or acetoxy group and in non-fluorinated dithienylcyclopentene bearing diethylamino group.

We recently reported that the novel NO-releasing O2-glycosylated diazeniumdiolates of structure 1 showed promising anti-parasitic activity against Leishmania major.1 While preparing some 2-deoxyglucose analogs for lead optimization, we have observed the facile displacement of acetate by bromide from the 4-position of peracetylated 2-deoxyglucose 2, as shown in Scheme 1, providing a convenient synthesis of 4-brominated 2,4-dideoxyglucose derivatives that would otherwise be difficult to access by currently preferred, directed synthetic routes. Scheme 1 In an effort to prepare compound 4a, peracetylated 2-deoxyglucose 2 was treated with HBr in glacial acetic acid. A tar assumed to be bromide 3 was formed and immediately reacted with diazeniumdiolate salt 5 to generate a product expected to be 4a. However, this easily crystallized, sharp-melting product was characterized by elemental analysis values that were vastly different from our expectation. Further examination revealed the presence of only two methyl singlets in the proton NMR, and mass spectrometry pointed to the presence of a bromine atom in the molecular ion isotopic cluster. Detailed analysis of the 1H NMR spectral properties showed that the halide had replaced the C4 acetoxy group with retention of configuration. Further work-up afforded 7a in 38% yield. The product 7a was deacetylated with methoxide in methanol to produce 7b. An alternate bromination procedure using BiBr3 and trimethylsilyl bromide gave 4-α-bromo-2,4-dideoxyglucosyl bromide diacetate 6, presumably the same glycosylating agent produced in the HBr/HOAc reaction. The reaction with BiBr3 was rapid, efficient, and gave a higher yield of 6 than the HBr procedure. Diazeniumdiolates generate up to two moles of NO upon hydrolysis under various conditions. Replacement of the C4 acetoxy group of compound 4b by bromine had little effect (only about three-fold) on hydrolysis rates at pH values of 14, 7.4, and 3.8–4.6 (Table 1), a key predictor of anti-leishmanial activity.1 Table 1 Half-lives of Hydrolysis at 37°C for Diazeniumdiolated Glycosides of Structure Et2NN(O)=NOR In conclusion, we have discovered a novel and simple BiBr3/TMS bromide-mediated preparation of compound 6, an extremely useful intermediate in the preparation of the 2-deoxy sugars primed for further functionality at C4. In particular, compounds 7a and 7b offer an electrophilic center at C4, making it potentially useful for further reaction with nucleophiles, including peptide chains or additional saccharides.

The comparison between measured and conformer-weighted calculated VCD spectra of the baccatin III ring of paclitaxel and visualization of the conformations using the new code for structure-activity relationships are reported for the first time. The VCD spectrum of paclitaxel closely resembles that of the baccatin III ring. The large characteristic nuCO VCD bands with bisignate signs (1732 cm-1, Deltaepsilon = -1.6 x 10(-1); 1715 cm(-1), Deltaepsilon = 2.4 x 10(-1)) strongly reflect the structural property of the family of conformations bacc-ABC32F defined using the new code. The comparison with the conformation of the baccatin III core in the electron micrograph of the crystal structure of tubulin-paclitaxel (1JFF) suggests a conformational change of paclitaxel corresponding to a switch through the binding with beta-tublin and the intermolecular interactions involving the hydroxyl group (D) and carbonyl of acetoxy group (E). The representation of conformational codes allows complicated conformations to be very easily compared and facilitates future computational analyses such as those for the large-molecule calculations as well as genome analysis.

Viral protein R (Vpr), an accessory gene of HIV-1, plays important roles in viral pathogenesis. Screening of Myanmar medicinal plants that are popular as primary treatments for HIV/AIDS and for HIV-related problems revealed the potent anti-Vpr activity of the CHCl3-soluble extract of Kaempferia pulchra rhizomes, in comparison with that of the positive control, damnacanthal. Fractionation of the active CHCl3-soluble extract led to the identification of 30 isopimarane diterpenoids, including kaempulchraols A-W (1-23). All isolates were assayed for anti-Vpr activity against TREx-HeLa-Vpr cells, in which Vpr expression is tightly regulated by tetracycline. Kaempulchraols B (2), D (4), G (7), Q (17), T (20), U (21), and W (23) exhibited potent anti-Vpr activity, at concentrations ranging from 1.56 to 6.25μM. The structure-activity relationships of the active kaempulchraols suggested that the presence of a hydroxy group at C-14 in an isopimara-8(9),15-diene skeleton and the presence of an acetoxy group at C-1 or C-7 in an isopimara-8(14),15-diene skeleton are the critical factors for the inhibitory effects against TREx-HeLa-Vpr cells.

We describe a novel trifluoroethanol (TFE) or hexafluoropropan-2-ol (HFP) mediated substitution reaction of the bay-region C10 acetoxy group in four stereoisomeric 7,8,9,10-tetraacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrenes (tetraol tetraacetates, two pairs of cis and trans isomers at the 9,10 positions) by the exocyclic N2-amino group of O6-allyl-3',5'-di-O-(tert-butyldimethylsilyl)-2'-deoxyguanosine (3). The tetraacetates are derived from cis and trans hydrolysis of (+/-)-7beta,8alpha-dihydroxy-9beta,10beta-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-1) and of (+/-)-7beta,8alpha-dihydroxy-9alpha,10alpha-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (B[a]P DE-2) at C-10 followed by acetylation. Excellent yields and high regioselectivity were observed. Similar cis/trans product ratios were observed for each set of cis and trans tetraol tetraacetates derived from DE-1 ( approximately 75/25) and from DE-2 (approximately 67/33) in HFP. This strongly suggests that the substitution proceeds via an SN1 mechanism involving a carbocation intermediate that is common to the cis and trans tetraacetates. Since it is likely that the cis and trans products from 3 arise from different conformations of the carbocation, its lifetime must be sufficiently long to permit conformational equilibration before its capture by the purine nucleophile. The corresponding reaction of (+/-)-9alpha-bromo-7beta,8alpha,10beta-triacetoxy-7,8,9,10-tetrahydrobenzo[a]pyrene with 3 in HFP was highly regio- and stereoselective and gave exclusively trans 10beta-adducts. This newly developed substitution reaction provides an attractive alternative synthetic strategy for the preparation of polycyclic hydrocarbon adducted oligonucleotide building blocks.

The reaction between carboxylic acids (RCOOH) and dialkyl dicarbonates [(R 1 OCO) 2 O], in the presence of a weak Lewis acid such as magnesium chloride and the corresponding alcohol (R 1 OH) as the solvent, leads to the esters RCOOR 1 in excellent yields. The mechanism involves a double addition of the acid to the dicarbonate, affording a carboxylic anhydride [(RCO) 2 O], R 1 OH and carbon dioxide. The esters arise from the attack of the alcohols on the anhydrides. Exploiting the lesser reactivity of tert-butyl alcohol in comparison with other alcohols, a clean synthesis of both carboxylic anhydrides and esters has been set up. In the former reaction, an acid/Boc 2 O molecular ratio of 2:1 leads to the anhydride in good to excellent yields, depending on the stability of the resulting anhydride to the usual workup conditions. In the latter reaction, stoichiometric mixtures of the acid and Boc 2 O are allowed to react with a twofold excess of a primary alcohol, secondary alcohol or phenol (R 2 OH) to give the corresponding esters (RCOOR 2 ). Purification of the products is particularly easy since all byproducts are volatile or water soluble. A very easy chromatography is required only in the case of nonvolatile alcohols. A broad variety of sensitive functional groups is tolerated on both the acid and the alcohol, in particular a high chemoselectivity is observed. In fact, no transesterification processes occur with the acid-sensitive acetoxy group and methyl esters.

The dehydration products of driman-8α,11-diol-11-monoacetate that are formed upon reaction with several dehydrating agents and the products from elimination of the C-8 acetoxy group in driman-8α,11-diol diacetate were investigated in detail. A new effective synthesis of drimenylacetate from driman-8α, 11-diol-11-monoacetate by its regioselective dehydration using methanesulfonic acid trimethylsilyl ether was developed.

A chromophore terminated aliphatic polyether was obtained by polymer analogous conversion of the amino groups of Jeffamine® ED-600 with 4-[5-(4-acetoxy-phenyl)-3-oxo-penta-1,4-dienyl]benzoic acid and subsequent saponification of the acetoxy group. UV/Vis spectroscopic investigations showed that deprotonation of the chromophoric groups by organic or inorganic bases as for example poly(1,8-octamethyleneacetamidine) and NaOH, respectively, results in a distinct bathochromic shift of the chromophores longest wavelength absorption band by about 100 nm. This effect is discussed in terms of polymer blends where the covalently bound chromophore can act as optical probe for acid-base interactions between the components.

α-Acetoxy (η3-allyl)palladium complexes were prepared from acyloxy functionalized allylsilanes under mild conditions and in good isolated yields. The substituent and ligand effects of the acetoxy group on the palladium–allyl bonding were studied by X-ray diffraction. These studies show that the acetoxy group generates a strongly deformed bonding between the metal atom and the allyl moiety. This unsymmetrical bonding is modulated by the σ-donor/π-acceptor properties of the ligands. The 13C NMR studies indicated that the shift values correlate with the carbon–palladium bond lengths and the inductive effects of the acetoxy group.