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Selenosugars are interesting targets of organic synthesis as they would possess potential biological activities. However, 4-selenotherofuranose derivatives, which have trans configuration for the two dihydroxy substituents at the 2,3-positions and a glycoside bond at the anomeric position, are not available in the current selenosugar library. In this study, racemic 4-selenothreofuranose derivatives were synthesized from trans-3,4-dioxygenated tetrahydroselenophenes in 77-99% yields with the α/β selectivity about 7:3 via oxidation and subsequent seleno-Pummerer rearrangement. The acetoxy group introduced at the anomeric position was then substituted with various nucleophiles, including activated 6-chloropurine, which afforded 4'-selenothreonucleoside derivatives, in the presence of BF3·OEt2 or TMSOTf. The stereochemistry of the selenosugar products was established by 1H NMR spectroscopy as well as X-ray analysis. The similar α/β selectivity observed in the latter glycosylation reaction to that in the former seleno-Pummerer rearrangement suggested the mediation of a common selenonium intermediate (-Se+=C

Palladium-catalyzed remote arylative substitution was achieved for the reaction of arylboronic acids with alkenes possessing a distant acetoxy group to provide arylation products having an alkene moiety at the remote position. The use of β-acetoxy elimination as a key step in the catalytic cycle allowed for regioselective formation of unstabilized alkenes after chain walking. This reaction was applicable to various arylboronic acids as well as alkene substrates.

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.

Seven new saikosaponins ( 1 − 7 ), together with four known ones ( 8 − 11 ), were isolated from the roots of Bupleurum chinense . Their structures were elucidated by comprehensive spectroscopic analysis and chemical methods. All obtained saikosaponins were oleanane-type, except for compound 11 , which was the first lupane–type saikosaponin isolated from the genus Bupleurum . Compound 1 represented the first example of saikosaponins bearing a hydroxyl group at C-15, while compound 4 was a saikosaponin containing acetoxy group at C-23 rarely found in genus Bupleurum . Compounds 6 and 7, bearing an n -butoxy moiety at C-11, were confirmed to be artifacts by LC–MS experiment. All the isolates were evaluated for their inhibitory effects towards nitric oxide production induced by lipopolysaccharide in BV-2 microglial cells, and saikosaponins A ( 9 ) and D ( 10 ) exhibited the most potent activity, which were comparable to the positive control dexamethasone.

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.

The total synthesis and evaluation of a key systematic series of vinblastines that incorporate the first deep-seated changes to the substituent at C4 are detailed. The synthetic approach features an expanded and redefined scope of a 1,3,4-oxadiazole [4 + 2]/[3 + 2] cycloaddition cascade in which electronically mismatched electron-deficient trisubstituted alkenes and unactivated trisubstituted alkenes were found to productively initiate the cycloaddition cascade with tethered electron-deficient 1,3,4-oxadiazoles. Such cycloaddition cascades were used to directly introduce altered C4 substituents, providing the basis for concise total syntheses of a series of C4 modified vindolines and their subsequent single-step incorporation into the corresponding synthetic vinblastines in routes as short as 8–12 steps. Evaluation of the synthetic vinblastines revealed a surprisingly large impact and role of the C4 substituent on activity even though it was previously not thought to intimately interact with the biological target tubulin. Only the introduction of a C4 methyl ester, a constitutional isomer of vinblastine in which the carbonyl carbon and ester oxygen of the C4 acetate are transposed, provided a synthetic vinblastine that matched the potency of the natural product. In contrast, even introduction of a C4 acetamide or N-methyl carboxamide, which incorporate single heavy atom exchanges (amide NH for ester oxygen) in vinblastine or the C4 methyl ester, provided compounds that were ≥10-fold less active than vinblastine. Other C4 acetate replacements, including a C4 amine, carboxylic acid, hydroxymethyl or acetoxymethyl group, led to even greater reductions in potency. Even replacement of the C4 acetoxy group or its equally active C4 methyl ester with an ethyl or isopropyl ester led to 10-fold or more reductions in activity. These remarkable trends in activity, which correlate with relative tubulin binding affinities, retrospectively may be ascribed to the role the substituent serves as a H-bond acceptor for α-tubulin Lys336 and Asn329 side chains at a site less tolerant of a H-bond donor, placing the methyl group of the C4 acetate or C4 methyl ester in a spatially restricted and well-defined hydrophobic half pocket created by a surrounding well-ordered loop. This remarkable impact of the C4 substituent, its stringency, and even the magnitude of its effect are extraordinary, and indicate that its presence was selected in Nature to enhance the effects of vinblastine and related natural products.

A tandem reaction of 4-(1-acetoxyallyl)-1-sulfonyl-1,2,3-triazole including formation of α-imino rhodium carbene, 1,2-migration of an acetoxy group and six electron electrocyclic ring closure was reported. The migration of the OAc group with excellent chemoselectivity was the crucial process, leading to the formation of 1,2-dihydropyridine specifically in up to 90% yield. Several transformations of the dihydropyridine product were also achieved illustrating the potential of the protocol in organic synthesis. Based on the observation of the intermediate, a plausible mechanism was proposed.

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.

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.

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.

Aromatic diyne systems bearing one terminal propargylic acetate moiety and one tertiary propargylic alcohol subunit were converted in the presence of a gold catalyst. After an initial 1,2-migration of the acetoxy group at the terminal alkyne, a gold carbenoid is formed which is then transferred onto the internal alkyne of the propargylic alcohol. This combination enables the use of propargylic acetates as precursors for a gold-catalyzed pinacol-type rearrangement. In the final pinacol-like step the shift of an alkyl or aryl moiety onto an electrophilic gold carbenoid/cation terminates the reaction and 1-naphthyl ketones are obtained as products. If electron-rich aromatic backbones are used, a mechanistically interesting alternative pathway including a retro-Buchner reaction is opened.

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.

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.

(17) O NMR is not routinely used for structure characterization, and kinetic studies of fluxional organic compounds are seldom undertaken because poor sensitivity and fast quadrupole relaxation are frequently regarded as intractable issues. This work shows how, nowadays, quantitative (17) O dynamic NMR studies on small organic molecules are feasible without enrichment being needed. It reports on acetoxysilanes, a class of fluxional compounds whose structure and dynamics were to be clarified. Natural abundance (17) O NMR spectra were recorded over a wide range of temperatures using standard instrumentation. The analysis relies on simple linewidth measurements and directly provides the activation parameters. The activation enthalpy is found to decrease with increasing number of acetoxy groups bound to silicon. Density functional theory calculations properly predict this trend and show that a single oxygen atom of the acetoxy group is bound to silicon, excluding chelation as binding mode, and that the dynamic process involves the shift of the silicon atom between the two oxygen atoms of the acetoxy group. Copyright © 2012 John Wiley & Sons, Ltd.

A series of 2-aryl-3-(4,5,6-trimethylpyrimidin-2-yl) thiazolidin-4-ones (1a–1c) and their derivatives bearing a lipophilic substituent, like acetoxy group (3a–3c), propionyloxy group (4a–4c), methyl (5d and 5e) at C-5 on thiazolidin-4-one ring were designed, synthesized and evaluated for their HIV-RT inhibitory activity. Using selfcatalyzed Pummerer reaction, compounds 3a–3c and 4a–4c were obtained in good yield (63.1%–75.2%). Preliminary anti-HIV-RT test of these derivatives indicated that compounds 1a–1c, 4b (propionyloxy group at C-5) showed moderate HIV-RT inhibitory activity and compounds 5d and 5e with methyl at C-5 showed a weak HIVRT inhibitory activity. Structure activity relationship analysis suggested that the substituted groups on C-5 would be unfavorable to anti-HIV-RT activity and that the steric effect might play a critical role in the anti-HIV RT activity.

A series of alkylacetates, R–COOCH3, with R- = n-propyl, isopropyl, n-butyl, isobutyl and amyl, was chlorinated photochemically in order to obtain mono-substituted products. Analysis of reaction samples was made by gas-liquid chromatography and identification of monochlorinated derivatives was performed by reference synthesis and N.M.R. spectroscopy. Experimental results showed an important activation for positions of the molecules substituted by electrodonor groups like methyl. On the contrary, positions substituted by electron withdrawing functions, like the acetoxy group, were desactivated. These results were correlated by a reactivity-structure relationship, showing the separation between inductive and resonance effects. The equation used was: with p* = -0.843 and h = +0.034. In view of the fact that the polar effect constants (σ*) for acetoxy and acetoxy-methylene groups were not known, these constants were determined: . The acetoxy sigma constant was considered as the sum of two terms: inductive (σ*−1) and mesomeric (σ*+M).

We have evaluated the antischistosomal activity of synthetic dihydrobenzofuran neolignans (DBNs) derived from (±)-trans-dehydrodicoumaric acid dimethyl ester (1) and (±)-trans-dehydrodiferulic acid dimethyl ester (2) against adult Schistosoma mansoni worms in vitro. Compound 4 ((±)-trans-4-O-acetyldehydrodiferulic acid dimethyl ester) displayed the most promising activity; at 200 μm, it kills 100 ± 0% of worms after 24 h, which resembles the result achieved with praziquantel (positive control) at 1.56 μm. The hydrogenation of the double bond between C7' and C8', the introduction of an additional methyl group at C3', and a double bond between C7 and C8 decreased the schistosomicidal activity of DBNs. On the other hand, the presence of the acetoxy group at C4 played an interesting role in this activity. These results demonstrated the interesting schistosomicidal potential of DBNs, which could be further exploited.

By use of 2D-QSAR and CoMFA approaches, a series of scalarane derivatives were assessed for which structural features confer antitubercular activity. The major contributions deduced from the 2D-QSAR models suggested positive effects on antitubercular activity of the shadow area on the XZ plane (representing the steric descriptor), the dipole moment, and relative positive charge (both representing the electrostatic descriptor). The contour map from the CoMFA model indicated the requirement for oxygenated functionality surrounding the furan moiety, particularly the extension of the acetoxy group either on C-16 toward the β plane or on C-19 toward the α plane. On the other hand, the region crowning C-12 was considered a sterically and negative-electrostatically disfavored area. Therefore, extension of a bulky negative functional group toward this area would diminish the binding interaction. The 2D-QSAR results agreed well with those from the CoMFA model and suggested the structural features of polarizable functionality that would enhance the antitubercular activity of the compounds in this series.

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 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.

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.

A simple approach to aromatization of steroidal quinols and epoxyquinols using a catalytic amount of TMSOTf is reported. Beside acetylation of the angular OH, the acid-catalyzed (TfOH) dienone-phenol rearrangement occurred affording "para" products, or in the case of blocked position 4, the acetoxy group 1,2-migration leads to the formation of "meta" products. Using epoxyquinol derivative as a substrate, the acetoxy group elimination was observed, followed by acid-catalyzed epoxy-ring opening and subsequent double bond migration, giving as a final product Delta(9,11) A-ring aromatized compounds. Synthesis of conduritol-like compounds and structure confirmation by X-ray crystallography of the precursor of steroidal conduritol is also described. In addition, the results of extensive antiproliferative screening against a panel of 60 cancer cell lines are presented. (c) 2005 Elsevier Inc. All rights reserved.

Root cultures of Tagetes patula L. cv. Carmen were grown with a mixture of unlabeled glucose and [U- 13 C 6 ]glucose or [1- 13 C 1 ]glucose as carbon source. Isoeuparin and (−)-4-hydroxytremetone were isolated by solvent extraction of the cultured tissue, purified by chromatography and analysed by 1 H and 13 C NMR spectroscopy. Amino acids obtained by hydrolysis of protein from the same experiments were used for the reconstruction of the labelling patterns in central metabolic intermediates. These labelling patterns were used for the prediction of isotopolog compositions in the benzofuranone derivatives via different hypothetical pathways. Comparison with the experimentally observed isotopolog distributions showed that the benzenoid ring and the acetoxy group are exclusively or predominantly (>98%) derived from phenylalanine and not from acetyl-CoA via a polyketide-type biosynthesis. The isopropylidene side chain and two carbon atoms of the furan and dihydrofuran moiety, respectively, originate from an isoprenoid building block obtained exclusively or predominantly (>98%) via the deoxyxylulose phosphate pathway. The exomethylene atom of the isopropylidene side chain is biosynthetically equivalent to the ( Z )-methyl group of dimethylallyl diphosphate. The data indicate that isoeuparin and (−)-4-hydroxytremetone are assembled from 4-hydroxyacetophenone and dimethylallyl diphosphate via prenyl-substituted 4-hydroxyacetophenone and dihydrobenzofurans as intermediates.

As part of our investigation into the structure–activity relationship of a novel class of aromatase inhibitors, two series of 3-deoxy androgens, androst-5-en-17-ones with a non-polar alkoxy ( 5 and 6 ), alkyl ( 20 − 22 ), or phenylalkyl ( 23 and 24 ) group at C-4β and 4-acyloxyandrost-4-en-17-ones ( 29 – 32 , and 34 ) were synthesized and evaluated. The 4β-alkyl and 4β-phenylalkyl compounds were obtained through reaction of 4α,5α-epoxy steroid ( 8 ) with RMgBr (R: alkyl and phenylalkyl) followed by dehydration of the 4β-substituted 5α-hydroxy products ( 15 − 19 ) with SOCl 2 as key reactions. Acylation of 4α,5α-diol ( 25 ) with (RCO) 2 O in pyridine and subsequent dehydration with SOCl 2 gave the 4-acyloxy steroids. All of the steroids studied, except for 4-acetoxy-19-ol ( 34 ) that was a non-competitive inhibitor of human placental aromatase, blocked aromatase activity in a competitive manner. 4-Benzoyloxy- and 4-acetoxy steroids ( 31 ) and ( 32 ) were the most powerful inhibitors of aromatase ( K i =70 and 60 nM, respectively). Elongation of an acetoxy group in a series of 4-acyloxy steroids or a methyl group in a series of 4β-alkyl steroids decreased affinity for aromatase principally in relation to carbon number of the acyl or alkyl function. The present findings are potentially useful for understanding the spatial and electronic nature of the binding site of aromatase as well as for developing effective aromatase inhibitors.

The 11 β-H epimer of Azadirachtin-I, isolated from the seed kernels of Azadirachta indica A. Juss (Neem), was characterized by both NMR and X-ray crystallographic techniques. NMR data reveals that the H11 proton is in β-orientation and the X-ray studies confirm this observation. The compound crystallized in space group P21 with the cell parameters a = 11.933(2) A, b = 7.752(5) A, c = 17.241(9) A, β = 106.80(3)○. Though the structural features are similar to the 11 β-H epimer of Azadirachtin-H, the orientation of the acetoxy group at C3 is different. The dihedral angle C9–C8–C14–O13, which describes the relative orientation of the modified decalin and modified furan moities of the molecule, is 23.3(8)○.

We present herein stereoselective synthesis of novel beta-lactams using polyaromatic imines following the Staudinger reaction. Consistent mechanisms for these results have been advanced. As a measure of cytotoxicity, some of these compounds have been assayed against nine human cancer cell lines. Structure-activity study has revealed that 1-N-chrysenyl and 1-N-phenanthrenyl 3-acetoxy-4-aryl-2-azetidinones have potent anticancer activity. The presence of the acetoxy group at C(3) of the beta-lactams has proven to be obligatory for their anticancer activity.

LC-ESI-MS analysis was carried out for taxoid profiling of partially purified methanol extracts of the stem bark of Taxus wallichiana growing in different regions of the Himalayas (Kashmir, Himachal Pradesh, UP hills, Sikkim and Arunachal Pradesh). Cone voltage fragmentation of the protonated, ammonium or sodium cationized molecular species resulted in diagnostic fragment ions. Thus, information about the number and nature of substituents and the taxane skeleton (whether it is normal or rearranged) was readily available from the LC-ESI-MS spectra. The rearranged 11(15-->1)-abeo-taxanes showed a characteristic elimination of the hydroxyisopropyl along with an acetoxy group. The identification of the taxoids was achieved by comparison of the ESI mass spectra with those of the authentic taxoids available to us or by interpreting the ESI mass spectra. The results were also corroborated by MS/MS analysis of the partially purified extract injected directly into the ESI source. Paclitaxel, its analogues and their xylosides are present in samples from all the regions. An interesting observation is the detection of a large number of basic taxoids having nitrogen-containing side chains.

We synthesized nucleoside analogues with a seven-membered moiety as the carbohydrate fragment mimicking the upper part of biologically active natural and synthetic nucleosides, starting from 3-iodomethyl-5-methoxy-1,4-dioxepane. The reaction sequence involved the substitution of the iodine atom by the acetoxy group, condensation with the nucleobases and subsequent saponification. The cis/trans mixtures of the target compounds were separated by reversed-phase preparative HPLC. The relative configurations of each of the hydrogen atoms of the cis and trans newly synthesized compounds were determined by spin decoupling, 2D NOESY and COSY experiments. None of this series showed activity in antiviral tests in cell cultures.

The addition of the phthalimidonitrene fragment, resulting from oxidation ofN-aminophthalimide by lead tetraacetate at −20 to −30°C, to the N=N-bond of 5-bromospirol[l-pyrazolinio-3,1′-cyclopropane] (1) affords, apart from the stable 5-bromo-N {spiro[l-pyrazolinio-3,1′-cyclopropane]}-N-phthalimidoamide (azimine2), regioisomeric azimine3, which is completely transformed into 3-acetoxy-N-{spiro[l-pyrazolinio-5,1′-cyclopropane]}-N-phthalimidoamide (4) under the reaction conditions. The acetoxy group in this product easily undergoes nuclcophilic substitution on treatment with McOH, NaN3, or the starting bromopyrazoline1. The structures of azimines obtained were established using NMR spectra, and the structure of the product of reaction of4 with1 was additionally proved by X-ray difraction data.

Two novel bacterial poly(3-hydroxyalkanoates) (PHAs) with either 3-hydroxy-7-oxooctanoate (HOO) and 3-hydroxy-5-oxohexanoate (HOH) or 8-acetoxy-3-hydroxyoctanoate (AHO), 6-acetoxy-3-hydroxyhexanoate (AHH), and 4-acetoxy-3-hydroxybutyrate (AHB) monomer units were produced at pilot scale. For the biosynthesis of these PHAs Pseudomonas oleovorans was cultivated at a 24 L scale in two-liquid-phase fed-batch processes using mineral salts medium and mixtures of 2-octanone/octane or n-octylacetate/octane as carbon sources. The bacterial accumulation of the polyesters was induced by nitrogen starvation and the addition of the substrate mixtures. Under these conditions, 26 and 45 g of PHA were isolated. The PHAs contained 10.3 and 3.3 mol % of oxo and acetoxy group monomers. Physical characterization was done with respect to their molecular weights, and thermal properties and similar results were found as for octane-based PHA. All monomer units have been identified by 2D 1H and 13C heteronuclear correlated NMR spe...

Nocardia sp. quantitatively converts salannin 1 and 3-de-O-acetylsalannin 2 (C-seco limonoids) into 3-deacetoxy-1-de[(E)-2-methylbut-2-enoyloxy]salannin-1-en-3-one 10, a novel and potentially bioactive compound with an α,β-unsaturated ketone moiety in ring ‘A’. In order to establish the sequence of events involved in this transformation and the structural specificity of this bacterial system, several new derivatives of salannin 1 have been prepared. These studies have indicated that the transformation is initiated by deacetylation at C-3, followed by oxidation of the secondary hydroxy group to 3-keto, which appears to facilitate the elimination of the tigloyloxy/acetoxy group at C-1 with the formation of an olefinic linkage between C-1 and C-2. The organism very efficiently transforms some of the derivatives of salannin into their corresponding compounds possessing an enone system in ring ‘A’, an essential pre-requisite for various biological activities. Some of the C-seco limonoids prepared in the present study, viz. 10, 1,2-didehydro-1,3-dideoxy-3-oxosalannic acid 18, 3-deacetoxy-1-de[(E)-2-methylbut-2-enoyloxy]-20,21,22,23-tetrahydrosalannin-1-en-3-one 15 and 1,2-didehydro-1,3-dideoxy-3-oxosalannol 23 were hitherto not known. p

The gas-phase elimination kinetics of the title compounds were examined over the temperature range 220.1 –349.0 °C and pressure range 19–120 Torr. These reactions proved to be homogeneous and unimolecular and to follow a first-order rate law. The overall rate coefficients are expressed by the following Arrhenius equations: for ­2-acetoxyacetic acid, logk1 (s−1) = (12.03 ± 0.28) − (170.8 ± 3.2) kJ mol−1 (2.303RT)−1; for 2-acetoxypropionic acid, logk1 (s−1) = (13.16 ± 0.24) − (174.2 ± 2.6) kJ mol−1 (2.303RT)−1 ; for 2-acetoxy-2-methylpropionic acid, logk1 (s−1) = (13.40 ± 0.72) − (160.9 ± 5.03) kJ mol−1 (2.303RT)−1. The products of the acetoxyacids are acetic acid, the corresponding carbonyl compound and CO gas, except for 2-acetoxy-2-methylpropionic acid, which undergoes a parallel elimination to give methacryclic acid and acetic acid. The rates of elimination are found to increase from primary to tertiary carbon bearing the acetoxy group. The mechanism appears to proceed through a discrete polar five-membered cyclic transition state, where the acidic hydrogen of the COOH assists the leaving acetoxy group, followed by the participation of the carbonyl oxygen for α-lactone formation. The unstable α-lactone intermediate decomposes rapidly into the corresponding carbonyl compound and CO gas. The importance of the acidic H of the COOH assistance in the acetoxy acid mechanisms may be revealed in the elimination kinetics of methyl 2-acetoxypropionate. This substrate was studied in the ranges 370.0 –430.0 °C and 36–125 Torr. This reaction is homogeneous, unimolecular and follows a first-order rate law. The products are methyl acrylate and acetic acid. The rate coefficients is given by the equation logk1 (s−1) = (12.63 ± 0.35) − (201.7 ± 4.4) kJ mol−1 (2.303RT)−1. Copyright © 2000 John Wiley & Sons, Ltd.

The crystal structure of the fully protected glycotripeptide N -benzyloxycarbonyl- O -(2,3,4,6-tetra- O -acetyl-β- d -galactopyranosyl)- l -threonyl-α-aminoisobutyryl-α-aminoisobutyric acid tert -butyl ester [Z-(β- d -GalAc 4 )- l -Thr-Aib-Aib-O t Bu] has been determined by X-ray diffraction. The peptide backbone is fully extended at Thr(1), left-handed helical at Aib(2), while it is right-handed helical at Aib(3). The fully extended conformation at the N-terminal Thr residue is stabilized by an intramolecular H-bond involving the N-1–H and O-1C-1 groups (intramolecularly H-bonded C 5 conformation). Two additional intramolecular H-bonds are observed, involving the peptide N–H groups of Aib(2) and Aib(3) as the donors, and the pyranosidic O-5 oxygen atom and the carbonyl oxygen atom of the acetoxy group on C-6 of the sugar, respectively, as the acceptors. Owing to the peptide–sugar H-bonds, the peptide backbone is forced to adopt a conformation dramatically different from the β-bend/3 10 -helical conformation usually observed for Aib-rich peptides. The implications and limitations of these findings on the effect of O -glycosylation on the conformation of natural peptides are briefly outlined.

In the title compounds, C(22)H(29)ClO(3), (I), and C(21)H(29)ClO(2), (II), respectively, the B rings adopt a half-chair conformation and the D rings adopt an envelope conformation. A twist of the steroid skeleton of both compounds is observed. There is a positional disorder of the acetoxy group of (II), with the terminal atoms disordered over two positions with near equal occupancy. Quantum-mechanical ab initio calculations using a molecular orbital Hartree-Fock method were performed for the isolated molecules, thus allowing the distinction within the structural features of these two androstane derivatives of which characteristics are intrinsic to the molecules and which are due to packing effects. The skeletal twisting was found to be innate to the molecules, while the acetoxy disorder is due to packing effects.

The synthesis of acetomycin and related analogs was investigated. Acetomycin was synthesized from diethyl allyl(methyl)malonate in 6.5% yield over 18 steps. The total number of steps was improved compared to our previous synthesis; i.e., four steps shorter, and the total yield was 4.5% greater than the previous synthesis. Acetomycin analogs with benzoyloxy and pivaloyloxy groups, instead of an acetoxy group at the 5-position of the gamma-butyrolactone ring were designed as esterase-resistant models and prepared similarly. Although they showed a similar level of cytotoxicity as acetomycin in vitro, they were not resistant to porcine liver esterase, and lost cytotoxicity in vivo.

A series of 7α-methoxy-2-[(substituted)methylene]cephem sulfones was synthesized. The compounds with an acetoxy group at the C-3′ position as a leaving group were found to be potent inhibitors of HLE. Selected compounds are also found to be antithrombin agents.

Asterriquinone (ARQ, 1a) is an antitumor metabolite of Aspergillus terreus IFO 6123. To gain insight into the structure-activity relationships of ARQ, a series of chemically modified derivatives (1-6), the ARQ analogues (b-e) and the 2, 5-dihydroxy-p-bezoquinone analogues (f-h), were prepared, and cytotoxic acitivity against mouse leukemia P388 cells investigated. Results indicated that : 1) at least one hydroxy group or acetoxy group in the p-benzoquinone moiety is important to exhibit cytotoxicity; 2) in the p-benzoquinone moiety, a single methoxy group and/or one aceotxy group substitution showed more potent cytotoxicity than when two hydroxy groups are substituted (1); 3) the indole ring is important for the cytotoxicity of ARQ analogues; 4) the 1, 1-dimethly-2-propenyl group in the indole ring is not important for the cytotoxic activity of ARQ.

The 3-trifluoromethyl derivatives of benzyl alcohol, benzyltrimethylsilane and phenoxytrimethylsilane undergo 2,6-photocycloaddition to cyclopentene to give the 1,11-disubstituted-tetracyclo[6.3.0.02,11.03,7]undec-9-enes 7, 10, 11 and 12. This specificity in isomer formation is considered to originate from an intramolecular attractive interaction between the 1,3-substituents on the arenes during the addition of the ethene and this causes an asymmetric distortion of the C6 ring which then controls the cyclopropane ring formation in the adduct. Similar reaction of 3-trifluoromethyl-phenol, -benzyl alcohol and -benzyltrimethylsilane, with vinyl acetate yields the 2-trifluoromethyl-endo-6-acetoxytricyclo[3.3.0.02,8]oct-3-enes 16, 17 and 18 respectively, showing that the directing influence of substituents on the arene dominates any effect of the acetoxy group on the photocycloaddition process. The control by Si· · ·F interaction is not, however, significant during the intramolecular photocycloaddition of the bichromophores 19 and 20 and only the 1,6-bridged dihydrosemibullvalene 24 and products derived from ortho cycloaddition are respectively formed.

Regiospecific replacement of acetoxy group in 2-(acetoxymethyl)-2-cyclohexenone 1 by stabilized carbanions, leads to S N 2 type products 2a-g , 5 and 6 . Bicyclic dienones 4 are prepared in “ one pot ” from the reaction of 2 with K 2 CO 3 in refluxing absolute ethanol.

Four analogs and two homologs of cocaine, designed as potent cocaine antagonists, were synthesized. The SN2 reaction between ecgonine methyl ester (13) or appropriately substituted piperidinol (19, 21) and appropriately substituted 4-iodobenzoyl chloride gave 4-iodobenzoyl esters of tropanes and piperidines (5-8). 2'-Hydroxycocaine (9) was obtained from 2'-acetoxycocaine (12) by selective transesterification with MeOH saturated with dry HCl gas. 2'-Acetoxycocaine (12) was synthesized from acetylsalicyloyl chloride (23) and ecgonine methyl ester (13). The binding affinities of these compounds were determined at the dopamine transporter for the displacement of [3H]WIN-35428. An iodo group substitution at the 4'-position of cocaine decreased dopamine transporter binding potency, while a hydroxy or acetoxy group at the 2'-position exhibited increased binding potency for the dopamine transporter compared to cocaine (10- and 3.58-fold, respectively). 2'-Hydroxylation also enhanced the bidning potency of 4'-iodococaine (5) by 10-fold. Replacement of the tropane ring with piperidine led to poor binding affinities.

The structures of O-acetyl-N-(5-phenyl-2-pyridyl)-hydroxylamine, C 13 H 12 N 2 O 2 , (I), and O-acetyl-N-(2-pyridyl)hydroxylamine, C 7 H 8 N 2 O 2 , (II), have been determined in order to confirm earlier structure assignments based on spectroscopic information. Compound (I) is the probable mutagenic metabolite of the phenylalanine pyrolysis product 2-amino-5-phenylpyridine. The crystal structures of (I) and (II) are the first reported for heterocyclic N-acetoxyarylamines, the corresponding homocyclic arylamine derivatives being extremely unstable. In the solid state, both (I) and (II) exist as hydrogen-bonded dimers, with the arylamine N atom acting as donor and the pyridine N atom of a neighboring inversion-related molecule as acceptor; the distance between donor and acceptor N atoms is 3.007 (2) in (I) and 2.956(2) A in (II). This orientation of the N-H bond results in the rotation of the acetoxy group out of the plane of the pyridine ring by 22.5 (2) in (I) and 27.4 (2)° in (II).

Trimeric sialic acid [Neu5Ac alpha(2-->8)Neu5Ac alpha(2-->8)Neu5Ac, 1] residue-containing gangliosides, GT4, alpha(2-->6)GT4 and GT3, have been synthesized for the first time. Methyl [phenyl] 5-acetamido-8-O-[5-acetamido-8-O-(5-acetamido-4, 7, 8, 9-tetra-O-acetyl-3, 5-dideoxy-D-glycero-alpha-D-galacto-2-nonulopyranosylono-1", 9'-lactone)-4,7-di-O-acetyl-3,5-dideoxy-D- glycero-alpha-D-galacto-2-nonulopyranosylono-1',9-lactone]-4,7-di- O-acetyl -3,5-dideoxy-2-thio-D- glycero-D-galacto-2-nonulopyranosid]onate (3) was prepared from 1, via lactonization, methyl esterification of the carboxyl group at the reducting end, O-acetylation and conversion of the anomeric acetoxy group into a phenylthio group. Iodonium-promoted glycosylation of 3 with 2-(trimethylsilyl)ethyl 2,6-di-O-benzyl-beta-D-galactopyranoside (5), 2-(trimethylsilyl)ethyl 3-O-benzyl-beta-D-galactopyranoside (6), 2-(trimethylsilyl)ethyl 2-O-benzoyl-3-O-benzyl-beta-D-galactopyranoside (9), and 2-(trimethylsilyl)ethyl 2, 3-di-O-benzyl-beta-D-galactopyranoside (11) gave the corresponding tetrasaccharides (13-15, 17) having the (Neu5Ac)3-Gal structure. The peracylated oligosaccharides 18 and 24 derived from 13 and 17, and the previously reported lactose derivative 29 were converted into the alpha-trichloroacetimidates 20, 26 and 31, and coupled with (2S,3R,4E)-2-azido-3-O-benzoyl-4-octadecene-1,3-diol (21) to afford the corresponding beta-glycosides 22, 27 and 32. These protected azidosphingosine derivatives were each transformed into the target gangliosides GT4, alpha(2-->6)GT4 and GT3 via selective reduction of the azido group, subsequent coupling with octadecanoic acid, O-deacylation and saponification of the methyl ester and lactone groups.

2,3,4-Tri-O-acetyl-5-thio-α- d -xylopyranosyl bromide was converted with zinc in the presence of 4-picoline into 3,4-di-O-acetyl-1,5-anhydro-5-thio- d -threo-pent-1-enitol 5. Treatment of 5 with N -iodosuccinimide—water in acetonitrile afforded a mixture which gave, after reduction with sodium borohydride—nickel chloride and subsequent acetylation, only 1,3,4-tri-O-acetyl-2,5-anhydro-5-thio- d -lyxitol. Deacetylation and subsequent benzoylation of 5 gave 3,4-di-O-benzoyl-1,5-anhydro-5-thio- d -threo-pent-1-enitol, the hydrogen bromide addition products of which were treated with sodium 4-cyanobenzenethiolate to give the anomeric mixture of the corresponding thioglycosides in low yield with an α,β-ratio of 3:7. When the mixture of the hydrogen bromide addition products was converted with silver acetate into their 1- O -acetates and condensation with 4-cyanobenzenethiol was performed in the presence of trimethylsilyl triflate, the thioglycosides were obtained in high yield with an α,β-ratio of 15:85. Deacetylation of this mixture afforded the title compound which showed high oral antithrombotic activity in rats. Conversion of methyl 2-deoxy-5-thio- d - threo -pentofuranoside into 2-deoxy-5-thio- d - threo -pentopyranose triacetate could be carried out in low yield only. Structures, including the conformation of the anomeric acetates and the thioglycosides, were determined by NMR spectroscopy. Because of the anomeric effect of the acetoxy group, the α-anomers are in the 4 C 1 conformation and the β-anomers in the 1 C 4 . Both anomeric thioglycosides were present in their 4 C 1 conformation.

F-ring opening in spirostanes with the 16β,22:22,25-diepoxy-23-acetoxymethyl-24-methyl side chain produces a Δ22-intermediate with an allylic acetoxy group. For this reason the reactivity profile of these compounds deviates from that observed in other naturally occurring or synthetic spirostanes and furospirostanes

pH-Controlled ozonolysis of the sodium nitronate forms of β- d -hexopyranosylnitromethanes (2,6-anhydro-1-deoxy-1-nitroheptitols) at room temperature produced the corresponding 2,6-anhydroheptoses. Without isolation, these glycosylated formaldehydes were converted by the conventional nitromethane route to the corresponding 2-(β- d -hexopyranosyl)nitroethenes (8a–c), via the intermediate acetylated 2-(β- d -hexopyranosyl)-2-hydroxynitroethanes. A spontaneous β-elimination of the acetoxy group vicinal to the nitro group occurred in acidic medium with the 2-acetamido-2-deoxy-β- d -glucopyranosyl derivative, but did not occur with the parent β- d -glucopyranosyl compound or its d - galacto or d - manno epimers. 2- C -Glycosylated nitroethenes were further transformed by a regioselective catalytic reduction to 2-(β- d -hexopyranosyl)nitroethanes.

From the root of Uvaria tonkinesis, six novel monotetrahydrofuran (THF) annoaceous acetogenins, tonkinins A, B and C and tonkinesins A, B and C, have been isolated and purified. Their structures, characterized by the presence of either a ketone or a hydroxyl group at C-5, were established on the basis of spectral evidence. The occurrence of two isomeric pairs, tonkinins A B and tonikinesins A B , is noteworthy. Tonkinin C and tonkinesin C are mono-THF type acetogenins with an unusual flanking acetoxy group adjacent on one side of the THF ring. The absolute stereochemistry of tonkinin C was revealed by the use of Mosher's methodology.