Communication: Double Bond Migration of a 1,5-Anhydro-3-C-p-Tolylsulfonyl-D-Hex-2-Enitol Derivative and the Corresponding 5a-Carba-Dl-Sulfonyl Sugar

Although the rate of proton abstraction (kinetic acidity) frequently plays an essential role in determination of reaction pathways and is of theoretical interest,¹ it is still controversial whether an oxygen atom activates or deactivates the abstraction of an α-hydrogen atom of an ether. For example, it is well known that oxidative elimination of a seleno group gives an allyl ether as the major product, indicating the oxygen atom deactivates the kinetic acidity.² Abstraction of the equatorial hydrogen atom at C-2 of 6-methyl-1,3-oxathiane-3,3-dioxide 1 is slower than that at C-4.³ On the other hand, the bridgehead hydrogen atom (H_b) adjacent to the oxygen atom of piperazinedione (2) is abstracted more readily than that of the alternative one (H_a).⁴     

Didemnaketals D and E,bioactive terpenoids from a Red Sea ascidian Didemnum species

Two new spiroketals, didemnaketals D (1) and E (2) were isolated from a marine ascidian species belonging to the genus Didemnum. The structures of the compounds were elucidated by extensive 1D (¹H, ¹³C, and DEPT) and 2D (COSY, TOCSY, HSQC, HMBC, NOESY, and ROESY) NMR studies and high-resolution mass spectroscopic data. The new didemnaketals differ from the reported ones in which that they lack the methyl functionality at C-6 and the hydroxy moiety at C-21. Instead, they possess an ester moiety at C-6 in addition to new oxygen functionality at C-20 of the didemnaketals. Compounds 1 and 2 were evaluated for their protein kinase inhibitory activity against different kinases (CDK5, CK1, DyrK1A, and GSK3) at 10 μg/mL. Compounds 1 and 2 showed moderate activity against these kinases. In addition, the compounds displayed moderate antimicrobial activity against Staphylococcus aureus and Bacillus subtilis, respectively.     

Synthesis and anti-HIV activity of 3-alkylamido-3-deoxy-betulinic acid derivatives

3-Alkylamido-3-deoxy-betulinic acids were synthesized and evaluated for anti-HIV activity as part of the structure-activity relationship study of the potent anti-HIV agent 3-O-(3',3'-dimethyl)-succinyl-betulinic acid (DSB) (2). 3Alpha-diglycorylamide-3-deoxy-betulinic acid demonstrated relatively potent anti-HIV activity (EC50 0.24 microm, TI 728). However, replacing the ester group at C-3 in 2 and its analogues with an amido group yielded inactive or much less potent compounds against HIV replication, indicating that the ester group at C-3 in 2-4 is essential for potent anti-HIV activity.     

Synthesis and central nervous system stimulant activity of camphor-1,2,4-benzotriazines fused with five and six-membered heterocycles

Novel camphor-1,2,4-triazines fused with imidazole 2–3 , thiadiazole 4 , 1,2,4-triazole 7 , pyrimidine 9–13 and 1,3,5-triazine 14 , were synthesized starting from (5R,8S)-3-amino-5,9,9-trimethyl-5,6,7,8-tetrahydro-5,8-methano-1,2,4-benzotriazine 1 . Evaluation of central nervous system stimulant activity demonstrated that the presence of a N-N group at C-3 position of 1,2,4-benzotriazine will be essential for the activity.     

New phenylboronic esters derived from inositol [1]

We have prepared two new tetracyclic phenylboronic esters 4 and 5 derived from myo-inositol and from 1,2-O-isopropylidene-myo-inositol, respectively. The structures of these compounds were established from NMR and IR spectra, elemental analyses, and an X-ray diffraction study in the case of 4 . Compound 4 is a tetracyclic derivative of the less stable conformer of inositol (five axial hydroxy groups and one equatorial) with two dioxaboroline rings at opposite faces of the six-membered ring, one formed between the boron atom and the axial hydroxyl groups at C-3 and C-5 and the other between the boron atom and the hydroxyl groups at C-4 and C-6, and a dioxaborolidine ring bridging C-1 and C-2 at axial and equatorial positions. A similar structure was found for 5 with the difference that bridging C-1 and C-2 there is a dioxolane ring. The boron atoms are planar with their attached atoms, stabilized by retrocoordination between the boron and oxygen and carbon atoms, respectively. The two phenyl rings that are in the same face of the molecule are essentially parallel, with a dihedral angle between planes of 28.26 ± 0.79°.     

Chiroptical studies of sugars. Part IV. Proposal of the glycosidic heteroatom [helicity rule in 1-thio-D-glycopyranosides

1-Thio-$\text{D}$-dlycopyranosides gave CD bands at 220 nm (n→δ^* of glycosidic sulfur). Their [θ] were shown as the sum of the two effects from ring oxygen and -OH at C-2, leading to the glycosidic heteroatom helicity rule to predict the configurations and conformations at C-1 and C-2.     

Electrochemical studies of biologically active indolizines

The electrochemical behavior of indolizine ethers, esters, tosylates, sulfonates and other indolizine and azaindolizine derivatives has been investigated by cyclic voltammetry and preparative electrolysis. The cyclic voltammetric data show that the E° values, taken as the midpoints between the anodic and cathodic peak potentials, are sensitive to the identities of the substituents at C-1, C-2 and C-7 positions. The E° values have been correlated with the Hammett substituent parameters. As expected, low E° values are seen for electron donating substituents and higher E° values are seen for electron withdrawing substituents. The cyclic voltammograms of indolizine derivatives with an oxygen atom connected to the C-1 position exhibit a one-electron reversible oxidation and a further, less well-defined, one-electron irreversible oxidation at higher E° values. The cyclic voltammograms of indolizines with hydrogen atom or thienyl substituents connected to the C-1 position exhibit only a one-electron irreversible oxidation. Electrochemical bulk oxidations of indolizines with an oxygen atom at the C-1 position afforded oxoindolizinium salts in decent yields, whereas indolizines with a hydrogen atom at C-1 afforded 1,1′ dimers of indolizines as products in good yields. Bulk oxidation of 1-(α-hydroxybenzyl)-2,3-diphenylindolizine-7-carbonitrile afforded an unexpected ketone product in which the carbonyl group of the indolizine is connected at C-8 instead of at the C-1 position of the starting material. The findings described herein support our hypothesis that certain indolizine derivatives may inhibit lipid peroxidation by an electron transfer mechanism.     

Actinoperylone, a novel perylenequinone-type shunt product, from a deletion mutant of the actVA-ORF5 and ORF6 genes for actinorhodin biosynthesis in Streptomyces coelicolor A3(2)

A novel shunt product, actinoperylone, has been isolated from a deletion mutant of the actVA-ORF5 and ORF6 genes involved in the biosynthesis of a benzoisochromanequinone (BIQ) antibiotic actinorhodin (ACT) in Streptomyces coelicolor A3(2). Spectroscopic analysis revealed its perylenequinone-type skeleton with the four chiral centers, obviously derived from the dimerization of an ACT intermediate. The structure of actinoperylone indicates the essential role of ActVA-ORF5 in the oxygen introduction at C-6, which is common to the formation of BIQ chromophore. The present results also agree with the distribution of the actVA-ORF5 homologues in all known BIQ biosynthetic clusters in streptomycetes.     

Mechanism of the formation of a dehydrated ion by an unusual loss of oxygen at the 4'-carbonyl group of abscisic acid methyl ester in electron ionization mass spectrometry

Methyl ester of abscisic acid (ABA), a plant hormone, gives a dehydrated ion at m/z 260 in electron ionization mass spectrometry (EI-MS). This dehydrated ion had been considered to be derived only from the elimination of the tertiary hydroxyl group at C-1'. We found that 34% of the dehydrated ion was formed by elimination of the oxygen atom at the 4'-carbonyl group, and the remaining 66% by elimination of the 1'-hydroxyl group. This unusual elimination of the carbonyl oxygen was shown with [4'-(18)O]ABA methyl ester. Involvement of the 4'-carbonyl oxygen in dehydration was observed in methyl ester of phaseic acid (PA), a natural metabolite of ABA, but not in 1'-deoxy-ABA methyl ester or isophorone. This suggested that the 1'-hydroxyl group was necessary for the elimination of the 4'-carbonyl oxygen. ABA methyl esters labeled with stable isotopes showed that hydrogen atoms at the 1'-hydroxyl group and at C-4 or -5 or -3' or - 5' or -7' were eliminated with the 4'-carbonyl oxygen. These results allow us to propose a formation mechanism of the dehydrated ion derived from the elimination of 4'-carbonyl oxygen and hydrogen atoms at C-4 and 1'-oxygen in ABA methyl ester as follows: first, ionization at the 1'-hydroxyl group occurs to give an ion radical, and the proton at the 1'-oxygen migrates to the 4'-carbonyl oxygen after the bond fission between C-1'-C-6'; second, migration of the proton at C-4 to the 1'-oxygen is followed by migration of the protons at C-5 and C-7' to C-4 and C-5, respectively; finally, the proton at the 1'-oxygen migrates to the 4'-hydroxyl group, and H(2)O at C-4' is eliminated to give the dehydrated ion. Our findings point out that a dehydrated ion is not always derived from the elimination of a hydroxyl group.     

Mechanism of 2-O→3-O silyl migration in cyclomaltohexaose (α-cyclodextrin)

To gain insight into the mechanism of the well-known 2-O→3-O silyl migration of 2-O-silylated cyclomaltooligosaccharides (cyclodextrins) under basic conditions, we have undertaken studies of the reaction of 2^A-O-TBDMSi-6^A-deoxy-6^A-S-phenyl-α-cyclodextrin with MeI and NaH. Under these conditions, the TBDMSi group on the C-2 oxygen was found to migrate onto the C-3 oxygen in the glucose residue in which the C-2 oxygen is located, and not onto the C-3 oxygen in the adjacent glucose residue.     

Birhodomolleins D and E,two new dimeric grayanane diterpenes with a 3-O-2′ linkage from the fruits of Rhododendron pumilum

Two dimeric grayanane diterpenes with a novel 3-O-2 linkage, birhodomolleins D (1) and E (2), were isolated and structurally elucidated from the fruits of Rhododendron pumilum. Their structures were fully determined by comprehensive analysis of spectroscopic data.     

New pentacyclic triterpene saponins with strong anti-leishmanial activity from the leaves of Maesa balansae

Six new triterpene saponins bearing an oxygen bridge between C-13 and C-28 and with pronounced anti-leishmanial activity were isolated from the methanolic extract of leaves of the Vietnamese medicinal plant Maesa balansae. The structure was established on the basis of detailed NMR (COSY, NOESY, HMQC, HMBC, TOCSY and DEPT) and FAB-MS studies along with chemical degradation. All saponins identified contained the same pentaglycosidic side chain, but a different esterification pattern on the triterpenoid part. Biological evaluation of the individual compounds against visceral leishmaniasis (Leishmania infantum amastigotes) revealed a much better activity in vitro compared to the reference compound Pentostam^®, which is currently used as first-line treatment for leishmaniasis.     

Vercytochalasins A and B: Two unprecedented biosynthetically related cytochalasins from the deep-sea-sourced endozoic fungus Curvularia verruculosa

Vercytochalasins A (1) and B (2), two biosynthetically related cytochalasins featuring novel structure and substituents, were isolated from the endozoic fungus Curvularia verruculosa which was associated with the deep-sea squat lobster Shinkaia crosnieri collected from the cold seep environment in South China sea. Their structures were elucidated by detailed interpretation of NMR spectroscopic and mass spectrometric data. The absolute configurations were confirmed by NOESY experiments as well as by DP4+ and ECD calculations. Differed from common cytochalasins, compound 1 is an uncommon secocytochalasin featuring the ester group cleaved between C-9 and C-23, and incorporating an additional oxygenated C4 unit which coupled with C-20 and C-22 to form a new substituted cyclohexenone moiety, while compound 2 contains an unusual 2?hydroxy-3-oxobutan-2-yl unit at C-22. Both compounds are distinctive from the commonly described cytochalasins. Compound 1 exhibited potent activity against angiotensin-I-converting enzyme (ACE) whereas compound 2 showed antibacterial activity. Molecular docking simulations were performed to explore the intermolecular interaction of compounds 1 and 2 with ACE.     

Directed ortho-lithiation of chloroquinolines. Application to synthesis of 2,3-disubstituted quinolines

2-, 3- and 4-Chloroquinolines were selectively lithiated at low temperature by lithium diisopropylamide at the more acidic C-3, C-4 and C-3 positions respectively. Reaction of 2-chloro-3-lithioquinoline with electrophiles led to various 2,3-disubsthuted quinolines. The versatility of this functionalization methodology is enhanced by the C-2 halogen reactivity towards oxygen or nitrogen nucleophiles. So, a great variety of 2,3-di-substituted quinolines were synthesized, such as 2-chloro, 2-alkoxy, 2-aminoquinolines or 2-quinolones bearing an hydroxy, carbonyl (aldehyde, ketone or carboxylic acid), iodo, trimethylsilyl or boronic acid moiety at the C-3. Some of the resulting 2,3-disubstituted synthons were annelated to tetracyclic polyaromatics, which possess the xanthone or indole structure. This could be achieved via further functionalization of the quinoline ring either by SNAr2 or heteroaromatic cross-coupling reactions, after the first directed-lithiation step.     

Antitumor activity of Pulsatilla koreana saponins and their structure-activity relationship

Seventeen saponins isolated from the root of Pulsatilla koreana were examined for their in vitro cytotoxic activity against the human solid cancer cell lines, A-549, SK-OV-3, SK-MEL-2, and HCT15, using the SRB assay method, and their in vivo antitumor activity using BDF1 mice bearing Lewis lung carcinoma (LLC). The saponins 5-17, with a free acidic functional group at C-28 of aglycon, exhibited moderate to considerable cytotoxic activity, however, the saponins 1-4, esterified with a trisaccharide at C-28 of aglycon, did not exhibit cytotoxic activity (ED50; >300 microM). Among them, oleanolic acid 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranoside (10) exhibited the most potent cytotoxic activity (ED50; 2.56, 2.31, 1.57, 8.36 microM, respectively). In vivo test, hederagenin 3-O-alpha-L-rhamnopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)]-alpha-L-arabinopyranoside (6, Inhibition Ratio, IR; 66.9%) exhibited more potent antitumor activity than taxol (IR; 35.8%) and doxorubicin (IR; 62.1%). Also, hedragenin 3-O-beta-D-glucopyranosyl-(1-->4)-O-beta-D-glucopyranosyl-(1-->3)-O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside (17, IR; 50.3%) exhibited potent antitumor activity. These two saponins were identically comprised of a hederagenin aglycon moiety and a sugar sequence O-alpha-L-rhamnopyranosyl-(1-->2)-alpha-L-arabinopyranoside at C-3 of the hederagenin, suggesting that the two elements are essential factors for the antitumor activity.     

Fluorine-Induced Pseudo-Anomeric Effects in Methoxycyclohexanes through Electrostatic 1,3-Diaxial Interactions

We report counter-intuitive axial preferences in non-stereochemically biased, selectively fluorinated methoxycyclohexanes. These pseudo-anomeric effects are apparent when electronegative CF₂ groups are placed at the C-2, C-4 and C-6 positions of the cyclohexane ring to render the C-3/5 axial hydrogen atoms electropositive. The electrostatic interaction between these axial hydrogen atoms and the -OMe oxygen is stabilising. The effect is explored using high-level ab initio and DFT calculations in the framework of NBO, QTAIM and NCI analysis across a range of derivatives, and experimentally (¹⁹F{¹H}-NMR at −80 °C) for some illustrative examples. The effect is significant in energy terms for a weak interaction, and illustrates a new stereoelectronic aspect attributed to selective fluorine substitution in organic chemistry.     

A taxane with a novel 9α,13α-oxygen bridge from Taxus cuspidata needles

A novel taxane with an unprecedented hemiacetal ring between C-13 and C-9 was isolated from the needles of Taxus cuspidata. The structure was characterized as (12αH)-2α,10β-diacetoxy-5α-cinnamoyloxy-9α,13α-epoxytax-4(20)-ene-11β,13β-diol (1). This is the first example of a natural taxane with a C-13 and C-9 oxygen bridge to form an unusual 6/8/6/6-membered ring system.     

Rearrangements in the Course of Fluorination by Diethylaminosulfur Trifluoride at C-2 of Glycopyranosides: Some New Parameters

Summary.  Reaction of a series of 21 glycosides unprotected at O-2 and featuring various configurations with DAST (diethylaminosulfur trifluoride) was monitored by ¹⁹F NMR spectroscopy. By means of the diacritical set of data (shift values and coupling constants) thus obtained for each product, identification of the operative mechanisms was possible. By correlation of these findings with stereochemical details from the structure of the educts, new parameters governing the choice of the reaction paths could be deduced. This evaluation led to the result that ring contraction after attack at C-2 of the ring oxygen and entry of the fluoride at C-1 is strongly favoured over all other possibilities. Exceptions are all derivatives of the manno series as well as all members of the trans-decalin type structure as present after 4,6-O-benzylidene acetal formation with educts having their ring substituents at C-4 and C-5 in diequatorial (trans) orientation. From these, α-D-mannopyranosides generally and of the trans-decalin types those with an additional 1,2-trans-configuration are prone to 1,2-aglycon migration and, again, entry of the fluoride at C-1. Additional pathways like alkoxy group migration, substitution under retention of configuration, or orthoester formation, are possible by participation of a suitably located neighbouring group at C-3 inasmuch as an alkoxy group interferes from an antiperiplanar orientation to the leaving group at C-2 and an acyloxy functionality attacks in a diequatorial relationship to the latter. The generally intended nucleophilic substitution by fluoride under inversion of configuration is of minor importance. Received November 26, 2001. Accepted November 28, 2001     

直接甲醇燃料电池的耐甲醇阴极电催化剂炭载四羧基酞菁钴的研究

比较了甲醇对Pt/C和炭载四羧基酞菁钴(CoPcTc/C)催化氧还原性能的影响.结果表明,甲醇使Pt/C催化氧还原的性能严重降低,而对经800℃热处理的CoPcTc/C(CoPcTc/C-800)基本没有影响;并且CoPcTc/C-800催化氧还原的性能优于经其它温度热处理的CoPcTc/C,CoPcTc/C-800是一种较好的直接甲醇燃料电池的耐甲醇阴极电催化剂.XPS结果表明,CoPcTc/C-800的活性位可能是含CoN₄结构的物质和零价Co的混合物.     

Synthetic UDP-galactofuranose analogs reveal critical enzyme-substrate interactions in GlfT2-catalyzed mycobacterial galactan assembly

Mycobacterial cell wall galactan, composed of alternating β-(1→5) and β-(1→6) galactofuranosyl residues, is assembled by the action of two bifunctional galactofuranosyltransferases, GlfT1 and GlfT2, which use UDP-galactofuranose (UDP-Galf) as the donor substrate. Kinetic analysis of synthetic UDP-Galf analogs identified critical interactions involved in donor substrate recognition by GlfT2, a processive polymerizing glycosyltransferase. Testing of methylated UDP-Galf analogs showed the donor substrate-binding pocket is sterically crowded. Evaluation of deoxy UDP-Galf analogs revealed that the C-6 hydroxyl group is not essential for substrate activity, and that interactions with the UDP-Galf C-3 hydroxyl group orient the substrate for turnover but appears to play no role in substrate recognition, making the 3-deoxy-analog a moderate competitive inhibitor of the enzyme. Moreover, the addition of a Galf residue deoxygenated at C-5 or C-6, or an l-arabinofuranose residue, to the growing galactan chain resulted in "dead end" reaction products, which no longer act as an acceptor for the enzyme. This finding shows dual recognition of both the terminal C-5 and C-6 hydroxyl groups of the acceptor substrate are required for GlfT2 activity, which is consistent with a recent model developed based upon a crystal structure of the enzyme. These observations provide insight into specific protein-carbohydrate interactions in the GlfT2 active site and may facilitate the design of future inhibitors.