- Synthesis of enantiomerically pure (R)-and (S)-1-benzoyloxypropane-2,3-diol and revision of the stereochemical outcome of the Candida antarctica lipase-catalyzed benzoylation of glycerol
-
Enantiomerically pure (R)- and (S)-1-benzoyloxypropane-2,3-diol have been prepared from (S)-(+)-2,2-dimethyl-1,3-dioxolane-4-methanol and used as reference compounds to correct the reported stereochemical outcome of the Candida antarctica lipase (CAL)-cat
- Casati, Silvana,Ciuffreda, Pierangela,Santaniello, Enzo
-
-
Read Online
- The Chiral Target of Daptomycin Is the 2R,2′S Stereoisomer of Phosphatidylglycerol
-
Daptomycin (dap) is an important antibiotic that interacts with the bacterial membrane lipid phosphatidylglycerol (PG) in a calcium-dependent manner. The enantiomer of dap (ent-dap) was synthesized and was found to be 85-fold less active than dap against
- Moreira, Ryan,Taylor, Scott D.
-
-
- Investigating the Individual Importance of the Pam2Cys Ester Motifs on TLR2 Activity
-
TLR2 agonists are at the forefront of vaccine research for a plethora of diseases, in particular they offer a promising tool for the treatment of cancer. A detailed knowledge of their structure–activity relationship informs the methodical design of vaccin
- Brimble, Margaret A.,Dunbar, P. Rod,Kelch, Inken D.,Li, Freda F.,Lu, Benjamin L.,Williams, Geoffrey M.
-
supporting information
p. 5415 - 5423
(2021/10/25)
-
- H-Phosphonate Synthesis and Biological Evaluation of an Immunomodulatory Phosphoglycolipid from Thermophilic Bacteria
-
The synthesis of a library of bacterial phosphoglycolipid, PGL-1, is described. Key features of the synthesis include regioselective esterification of the primary alcohol of the diacylglycerol moiety and an H-phosphonate method to install the phosphate in PGL-1 in comparison with earlier reported procedures. A representative set of PGL-1 analogues was prepared and evaluated for their biological activities. Results showed that the immunological activity of PGL-1 is dependent on the chain lengths of the fatty acids.
- Gan, Chin Heng,Hua, Kuo-Feng,Lam, Yulin,Li, Lan-Hui,Peng, Yi-Jen,Wei, Chih-Feng,Wijaya, Hadhi,Wu, Shih-Hsiung
-
-
- Preparation, supramolecular aggregation and immunological activity of the bona fide vaccine adjuvant sulfavant S
-
In aqueous conditions, amphiphilic bioactive molecules are able to form self-assembled colloidal structures modifying their biological activity. This behavior is generally neglected in preclinical studies, despite its impact on pharmacological development. In this regard, a significative example is represented by a new class of amphiphilic marine-inspired vaccine adjuvants, collectively named Sulfavants, based on the β-sulfoquinovosyl-diacylglyceride skeleton. The family includes the lead product Sulfavant A (1) and two epimers, Sulfavant R (2) and Sulfavant S (3), differing only for the stereochemistry at C-2 of glycerol. The three compounds showed a significant difference in immunological potency, presumably correlated with change of the aggregates in water. Here, a new synthesis of diastereopure 3 was achieved, and the study of the immunomodulatory behavior of mixtures of 2/3 proved that the bizarre in vitro response to 1–3 effectively depends on the supramolecular aggregation states, likely affecting the bioavailability of agonists that can effectively interact with the cellular targets. The evidence obtained with the mixture of pure Sulfavant R (2) and Sulfavant S (3) proves, for the first time, that supramolecular organization of a mixture of active epimers in aqueous solution can bias evaluation of their biological and pharmacological potential.
- Manzo, Emiliano,Fioretto, Laura,Gallo, Carmela,Ziaco, Marcello,Nuzzo, Genoveffa,D’Ippolito, Giuliana,Borzacchiello, Assunta,Fabozzi, Antonio,de Palma, Raffaele,Fontana, Angelo
-
-
- MACROCYCLIC CHELATORS AND METHODS OF USE THEREOF
-
Macrocyclic chelators (I) for chelation of alpha-emitting radiometal ions, such as actinium-225 are provided. Also provided are radiometal complexes containing an alpha-emitting radiometal ion bound to the macrocyclic chelator via coordinate bonding, and radioimmunoconjugates containing the radiometal complexes covalently linked to a targeting ligand, such as an antibody or antigen binding fragment thereof. The radioimmunoconjugates can be produced by click chemistry reactions. Methods of using the radiocomplexes and radioimmunoconjugates for selectively targeting neoplastic cells for radiotherapy and for treating neoplastic diseases and disorders are also described.
- -
-
Page/Page column 99; 102; 139; 140
(2020/11/30)
-
- Synthesis of enantiopure ABC-type triacylglycerols
-
The synthesis of twelve enantiopure structured triacylglycerols (TAGs) of the ABC type possessing three different fatty acids is described by a six-step chemoenzymatic approach starting from (S)-solketal. Eight of the TAGs possess two different saturated fatty acyl groups located in the sn-1 and sn-2 positions with an unsaturated fatty acyl group in the remaining sn-3 position of the glycerol skeleton, whereas the remaining four possess two different saturated acyl groups in the terminal sn-1 and sn-3 positions with an unsaturated acyl group in the sn-2 position. The former group was synthesised by a six-step chemoenzymatic route involving a highly regioselective immobilised Candida antarctica lipase. The second group was prepared by a similar six-step approach, that required two separate lipase steps. Such enantiopure TAGs are strongly demanded as standards for enantiospecific analysis of intact TAGs in fats and oils.
- Gudmundsson, Haraldur G.,Linderborg, Kaisa M.,Kallio, Heikki,Yang, Baoru,Haraldsson, Gudmundur G.
-
-
- COMPOUNDS, DERIVATIVES, AND ANALOGS FOR CANCER
-
The instant invention provides for inositol derivatives, analogs, methods of preparation and uses that inhibit oncogenic signaling pathways and genes. In particular, the compounds disclosed selectively inhibit one or two classes and or isoforms of PI3K. T
- -
-
Paragraph 0031; 0188
(2020/02/16)
-
- Synthesis and enantiospecific analysis of enantiostructured triacylglycerols containing n-3 polyunsaturated fatty acids
-
The stereospecific structure of triacylglycerols (TAGs) affects the bioavailability of fatty acids. Lack of enantiopure reference compounds and effective enantiospecific methods have hindered the stereospecific analysis of individual TAGs. Twelve novel enantiostructured AAB-type TAGs were synthesized containing one of the three n-3 polyunsaturated fatty acid: α-linolenic acid (ALA), eicosapentaenoic acid (EPA), or docosahexaenoic acid (DHA) in sn-1 or sn-3 position. These compounds formed six enantiomer pairs, which were separated with recycling high-performance liquid chromatography using chiral columns and UV detection. The chromatographic retention behavior of the enantiomers and the stereospecific elution order were studied. The enantiomer with an n-3 PUFA in the sn-1 position eluted faster than the enantiomer with the n-3 PUFA in the sn-3 position, regardless of the carbon chain length and number of double bonds of the PUFA. TAG enantiomers containing DHA exhibited highly different retention on the chiral column and were separated after the first column, whereas recycling was needed to separate the enantiomer pairs containing ALA or EPA. The system using two identical columns and one mobile phase, without sample derivatization, proved to be very effective also for peak purity assessment, confirming the enantiopurity of the synthesized structured TAGs being higher than 98 percent (96 percent ee).
- Gudmundsson, Haraldur G.,Haraldsson, Gudmundur G.,Kallio, Heikki,Kalpio, Marika,Linderborg, Kaisa M.,Magnússon, Jóhann D.,Yang, Baoru
-
-
- PHOSPHOLIPID COMPOUND CONTAINING UNSATURATED FATTY ACID DERIVATIVE HAVING CYCLOPROPANE RING
-
The present invention aims to provide a medicine having a cognitive function improving effect and an anti-diabetes action. A phospholipid compound containing unsaturated fatty acid having a cyclopropane ring such as 8-[2-(2-pentyl-cyclopropylmethyl)-cyclopropyl]-octanoic acid (DCP-LA) and 8-(2-octylcyclopropyl)octanoic acid (DCP-OA) and the like, particularly 1,2-o-bis-[8-{2-(2-pentyl-cyclopropylmethyl)-cyclopropyl}-octanoyl]-sn-glycero-3-phosphatidylethanolamine (diDCP-LA-PE), has a cognitive function improving effect and an anti-diabetes action, and is useful as a medicine such as a therapeutic drug for dementia, a therapeutic drug for diabetes and the like.
- -
-
Paragraph 0063; 0064
(2016/01/11)
-
- SUBSTITUTED SPIROPYRIDO[1,2-a]PYRAZINE DERIVATIVE AND PHARMACEUTICAL USE OF SAME AS HIV INTEGRASE INHIBITOR
-
Provided is a substituted spiropyrido[1,2-a]pyrazine derivative or a pharmaceutically acceptable salt thereof, which is useful as an anti-HIV agent. The present invention relates to a compound represented by the following formula [I] or [II] or a pharmace
- -
-
Paragraph 1548; 1595; 1596; 1597
(2014/08/19)
-
- Synthesis of phosphoramidites of isoGNA, an isomer of glycerol nucleic acid
-
IsoGNA, an isomer of glycerol nucleic acid GNA, is a flexible (acyclic) nucleic acid with bases directly attached to its linear backbone. IsoGNA exhibits (limited) base-pairing properties which are unique compared to other known flexible nucleic acids. He
- Kim, Keunsoo,Punna, Venkateshwarlu,Karri, Phaneendrasai,Krishnamurthy, Ramanarayanan
-
p. 2131 - 2138
(2015/02/19)
-
- Optically active monoacylglycerols: Synthesis and assessment of purity
-
Despite their simple structures, synthesis of 1(or 3)-acyl-sn-glycerols remains a challenge that cannot be ignored because of facile acyl migrations, which not only complicate the synthesis but also make direct GC or HPLC analysis unfeasible. Assessment of the optical purity of monoacylglycerols has, to date, relied almost exclusively on specific rotation data, which are small in value and thus insensitive to impurities. Now, a simple means to "magnify" the small specific rotations has been found, along with practical methods for the measurement of both 1,2-and 1,3-acyl migrations, which offer a convenient and straightforward alternative to Mori's NMR analysis of Mosher esters. With the aid of these methods, a range of conditions for deacetonide removal were examined en route to the synthesis of two natural monoacylglycerols. Refined hydrolysis conditions, along with useful knowledge about the solubility and reactivity of substrates with an ultra long alkyl chain are also presented. Copyright
- Chen, Chao-Yuan,Han, Wei-Bo,Chen, Hui-Jun,Wu, Yikang,Gao, Po
-
p. 4311 - 4318
(2013/07/26)
-
- PHOSPHATIDYLINOSITOL
-
The invention relates to a new pharmaceutical compound, diacyl phosphatdylinositol in which both the sn-1 and the sn-2 place are taken by stearic acid (18:0) (diacyl [18:0; 18:0] phosphatidylinositol), more preferably, wherein said diacyl phosphatidylinositol is compound 1 as depicted in Fig. 10 or a racemate of compounds 1 and 2 as depicted in Fig. 10. Said pharmaceutical compound and pharmaceutical compositions comprising this compound are specifically useful for the treatment of a disease or a condition wherein suppression of T-cell activation is desirable, such as asthma, diabetes Type 1, rheumatoid arthritis, inflammatory bowel disease or psoriasis. Also part of the invention are food items containing the compound(s) of the invention and use thereof in a diet to treat or prevent the disease or condition mentioned above
- -
-
Page/Page column 20; 21
(2013/06/27)
-
- Diaryldiazepine Prodrugs for the Treatment of Neurological and Psychological Disorders
-
The present invention provides prodrug compounds of diaryldiazepine drug compounds.
- -
-
Page/Page column 70
(2011/07/29)
-
- Structure-activity relationships in toll-like receptor-2 agonistic diacylthioglycerol lipopeptides
-
The N-termini of bacterial lipoproteins are acylated with a (S)-(2,3-bisacyloxypropyl)cysteinyl residue. Lipopeptides derived from lipoproteins activate innate immune responses by engaging Toll-like receptor 2 (TLR2) and are highly immunostimulatory and yet without apparent toxicity in animal models. The lipopeptides may therefore be useful as potential immunotherapeutic agents. Previous structure-activity relationships in such lipopeptides have largely been obtained using murine cells, and it is now clear that significant species-specific differences exist between human and murine TLR responses. We have examined in detail the role of the highly conserved Cys residue as well as the geometry and stereochemistry of the Cys-Ser dipeptide unit. (R)-Diacylthioglycerol analogues are maximally active in reporter gene assays using human TLR2. The Cys-Ser dipeptide unit represents the minimal part-structure, but its stereochemistry was found not to be a critical determinant of activity. The thioether bridge between the diacyl and dipeptide units is crucial, and replacement by an oxoether bridge results in a dramatic decrease in activity.
- Wu, Wenyan,Li, Rongti,Malladi, Subbalakshmi S.,Warshakoon, Hemamali J.,Kimbrell, Matthew R.,Amolins, Michael W.,Ukani, Rehman,Datta, Apurba,David, Sunil A.
-
experimental part
p. 3198 - 3213
(2010/10/02)
-
- A synthesis of dioctanoyl phosphatidylinositol
-
A synthesis of the naturally occurring enantiomer of phosphatidylinositol is reported. A resolution strategy, using camphor as a chiral auxiliary is employed to obtain the desired, enantiomerically pure, inositol derivative. Dioctanoyl lipid chains are appended to the molecule, which are shorter than the naturally occurring lipid chains, providing the molecule with enhanced water solubility.
- Elliott, Thomas S.,Nemeth, Joseph,Swain, Simon A.,Conway, Stuart J.
-
scheme or table
p. 2809 - 2813
(2010/03/30)
-
- ONE-POT SYNTHESIS OF ALPHA/BETA-O-GLYCOLIPIDS
-
The present invention provides a one-pot method of preparing an unprotected α-O-glycolipid. The first step involves contacting a protected α-iodo sugar with a catalyst and a lipid comprising a hydroxy group, under conditions sufficient to prepare a protected α- O-glycolipid. The second step involves deprotecting the protected α-O-glycolipid under conditions sufficient to prepare the unprotected α-O-glycolipid, wherein the contacting and deprotecting steps are performed in a single vessel. The present invention also provides a one-pot method of preparing an unprotected β-O-glycolipid following the steps for the preparation of the unprotected α-O-glycolipid.
- -
-
Page/Page column 19
(2008/12/04)
-
- Synthesis, pharmacology, and cell biology of sn-2-aminooxy analogues of lysophosphatidic acid
-
An efficient enantioselective synthesis of sn-2-aminooxy (AO) analogues of lysophosphatidic acid (LPA) that possess palmitoyl and oleoyl acyl chains Is presented. Both sn-2-AO LPA analogues are agonists for the LPA1, LPA2, and LPAsu
- Gajewiak, Joanna,Tsukahara, Ryoko,Fujiwara, Yuko,Tigyi, Gabor,Prestwich, Glenn D.
-
scheme or table
p. 1111 - 1114
(2009/04/07)
-
- Chemoenzymatic synthesis of enantiopure structured triacylglycerols
-
A highly efficient chemoenzymatic method for the synthesis of enantiopure ABC-type asymmetrically structured triacylglycerols has been developed starting from enantiopure (S)-solketal and involving two lipase steps. Georg Thieme Verlag Stuttgart.
- Kristinsson, Bj?rn,Haraldsson, Gudmundur G.
-
scheme or table
p. 2178 - 2182
(2009/06/18)
-
- Glycerophosphoric acid ester derivative having polyfunctional metal chelate structure
-
A compound represented by the following general formula (I), or a salt thereof: wherein R1 and R2 independently represent a substituted or unsubstituted alkyl or alkenyl group having 8 to 30 carbon atoms; L represents a divalent bridging group (L is constituted by atoms selected from the group consisting of carbon atom, oxygen atom, nitrogen atom and hydrogen atom, wherein the total number of atoms constituting L and selected from the group consisting of carbon atom, oxygen atom and nitrogen atom is 4 to 15); and Ch represents a chelate forming moiety containing 3 or more nitrogen atoms. A compound suitable for a liposome contrast medium for performing lesion-selective imaging is provided.
- -
-
Page/Page column 13-14
(2008/06/13)
-
- Efficient, one-pot syntheses of biologically active α-linked glycolipids
-
Per-O-silylated galactosyl iodides undergo α-glycosidation with fully functionalized glycolipids producing biologically relevant conjugates. The Royal Society of Chemistry.
- Du, Wenjun,Kulkarni, Suvarn S.,Gervay-Hague, Jacquelyn
-
p. 2336 - 2338
(2008/02/09)
-
- Self-assembled nanoreactors as highly active catalysts in the hydrolytic kinetic resolution (HKR) of epoxides in water
-
CoIII(salen) complexes have been immobilized on amphiphilic block copolymers, which self-assemble in water to give micellar aggregates with a hydrophobic Co(salen) core and a water-soluble shell (see picture). These aggregates were used to catalyze the hydrolytic kinetic resolution (HKR) of racemic aromatic epoxides over four consecutive cycles and gave the epoxides in up to 99 % ee. H2salen = N,N′-bis(salicylidene)ethylenediamine. (Chemical Equation Presented).
- Rossbach, Benjamin M.,Leopold, Kerstin,Weberskirch, Ralf
-
p. 1309 - 1312
(2007/10/03)
-
- Conversion of Epoxides to 1,3-Dioxolanes Catalyzed by Tin(II) Chloride
-
Anhydrous tin(II) chloride is an efficient catalyst for the reaction of epoxides with acetone to prepare 2,2-dimethyl-1,3-dioxolanes (acetonides) in good to excellent yields. Mono-, di-, and trisubstituted epoxides participate equally well in this diastereospecific reaction. The use of single enantiomer epoxides under the reported conditions results in significant erosion of optical activity.
- Vyvyan, James R.,Meyer, Jennifer A.,Meyer, Korin D.
-
p. 9144 - 9147
(2007/10/03)
-
- Process for the preparation of 1,3-dioxolane-4-methanols
-
PCT No. PCT/JP97/03166 Sec. 371 Date Feb. 8, 1999 Sec. 102(e) Date Feb. 8, 1999 PCT Filed Sep. 9, 1997 PCT Pub. No. WO98/11088 PCT Pub. Date Mar. 19, 1998A process for preparing a 1,3-dioxolane-3-methanol (5) in a racemic form or an optically active form involves reacting with an alcohol in a base (i) a 3-halogeno-1,2-propanediol (1a) in which X is halogen atom, or (ii) a glycidol effecting a 3-alkoxy-1,2-propanediol, acetalizing the 3-alkoxy-1,2-propanediol in an acid, and hydrogenolyzing the resulting 4-alkoxy-1,3-dioxolane in a reduction catalyst to effect the 1,3-dioxolane-3-methanol (5) in which each of R1 and R2 is a hydrogen atom, alkyl having 1 to 4 carbon atoms or phenyl, or R1 and R2 together form a cycloalkyl ring having 3 to 6 carbon atoms.
- -
-
-
- Process for preparation of 1,3-dioxolane-4-methanol compounds
-
PCT No. PCT/JP97/03165 Sec. 371 Date Feb. 8, 1999 Sec. 102(e) Date Feb. 8, 1999 PCT Filed Sep. 9, 1997 PCT Pub. No. WO98/11087 PCT Pub. Date Mar. 19, 1998A process for preparing easily and economically a 1,3-dioxolane-4-methanol compound in a racemic form or an optically active form with high purity and in high yield. The process comprises reacting an alkali metal or alkaline earth metal salt of an alcohol or a carboxylic acid with a halogenomethyl-1,3-dioxolane which is prepared by acetalizing a halogeno-1,2-propanediol of a formula (1) wherein X is a halogen atom, in an acid catalyst to conduct esterification or etherification, and then hydrolyzing the ester group and hydrogenolyzing the ether group to prepare a 1,3-dioxolane-4-methanol compound of a formula (5) wherein R1 and R2 are hydrogen atom, alkyl having 1 to 4 carbon atoms or phenyl, and R1 and R2 may form a cycloalkyl ring having 3 to 6 carbon atoms with the adjacent carbon atoms.
- -
-
-
- Structural determination of sulfoquinovosyldiacylglycerol by chiral syntheses
-
Chiral sulfoquinovosyldiacylglycerols (SQDGs) have been synthesized to determine the absolute stereochemistry and the biological activities. The 1 H NMR spectrum of a natural SQDG is comparable to that of synthetic (2S)-SQDG rather than that of the (2R) analogue. The biological activity of the respective isomers for DNA polymerase α and β inhibition was not distinguishable in the enzymatic assay.
- Hanashima, Shinya,Mizushina, Yoshiyuki,Yamazaki, Takayuki,Ohta, Keisuke,Takahashi, Shunya,Koshino, Hiroyuki,Sahara, Hiroeki,Sakaguchi, Kengo,Sugawara, Fumio
-
p. 4403 - 4407
(2007/10/03)
-
- Diacylglycerols with lipophilically equivalent branched acyl chains display high affinity for protein kinase C (PK-C). A direct measure of the effect of constraining the glycerol backbone in DAG lactones
-
New synthetic diacylglycerols (DAGs) with equivalent branched acyl chains were compared with commercially available DAGs as PK-C ligands. The results support the view that there is a minimal lipophilic requirement provided by the equivalent acyl groups th
- Nacro, Kassoum,Bienfait, Bruno,Lewin, Nancy E.,Blumberg, Peter M.,Marquez, Victor E.
-
p. 653 - 655
(2007/10/03)
-
- Synthesis of (6S,7S,9R,10R)-6,9-epoxynonadec-18-ene-7,10-diol, a marine epoxy lipid isolated from the brown alga, Notheia anomala, by an oxiranyl anion strategy
-
The stereocontrolled synthesis of (6S,7S,9R,10R)-6,9-epoxynonadec-18- ene-7,10-diol, isolated from the brown alga, Notheia anomala, has been achieved. The key 2,3,5-trisubstituted tetrahydrofuran ring was constructed by alkylation of the sulfonyl-stabilized oxiranly anion followed by 5-endo cyclization.
- Mori, Yuji,Sawada, Tomoko,Furukawa, Hiroshi
-
p. 731 - 734
(2007/10/03)
-
- Synthesis of a small library of mixed-acid phospholipids from D-mannitol as a homochiral starting material
-
Synthesis of a series of mixed-acid phospholipids containing a polyunsaturated fatty acid using a newly protecting strategy are described. Thus, benzyl and methyl α-(2,4-dinitrophenyl)acetic acid which were respectively removed by BCl3 and 354 nm light are used as protecting groups.
- Xia, Jie,Hui, Yong-Zheng
-
p. 1659 - 1663
(2007/10/03)
-
- Synthesis of diacylglycerol analogs of phosphatidylinositol 3,4,5- trisphosphate
-
Phosphatidylinositol 3,4,5-trisphosphate analogs with saturated diacylglycerol substructure have been designed, focusing on their reactivity with PIP3 5-phosphatase. Dephosphorylation of native PIP3 was competitively inhibited in the presence of synthetic PIP3(C2) and PIP3(C4), respectively.
- Shirai, Ryuichi,Morita, Koji,Nishikawa, Asuka,Nakatsu, Noriyuki,Fukui, Yasuhisa,Morisaki, Naoko,Hashimoto, Yuichi
-
p. 9485 - 9488
(2007/10/03)
-
- An expeditious route to Streptococci and Enterococci glycolipids via ring-opening of 1,2-anhydrosugars with protic acids
-
1,2-Anhydroglucose 6 reacts smoothly and with a high degree of stereoselectivity with a variety of carboxylic and phosphoric acids resulting in the formation of the predominantly β-oriented 1-O-acyl and 1-O-phosphorylglucoses 7-17. This methodology has been successfully applied in the construction of glycolipids 1a,b. Ring-opening of the 1,2-anhydroglucose derivative 19 with benzoic acid furnished exclusively the β-aligned key intermediate 20. Subsequent ICDT-assisted chemoselective α-glucosylation of 20 with thioethyl donor 21, followed by glycosidation of kojibiosyl benzoate 22 with glycerol acceptor 23 gave the fully protected α-diglucosyl glycerol derivative 25, which upon desilylation (→28), acylation (→29 or 30) and deprotection afforded the target glycolipids 1a-b in high overall yield.
- Timmers,Van Straten,Van Der Marel,Van Boom
-
p. 471 - 487
(2007/10/03)
-
- Synthesis of chiral 3E,5E-octadiene-1,2R-7R,8-tetraol frameworks by means of palladium(II)-promoted hetero-Claisen rearrangement: Mechanistic aspect
-
A plausible mechanism has been proposed for the exclusive formation of symmetrical dienediol such as 1,6-bis(acetoxy)-2,4-diene in palladium(II)-promoted [3,3]sigmatropic rearrangement of 3,4-bis(acetoxy)-1,5-diene system. This mechanism referred to as migration-induced intramolecular dioxanium ion switching (MIDIS) process can reasonably explain why the vicinal acetoxy groups move from 3,4-position and not to 5,6- but two directionally to 1,6-position.
- Saito, Seiki,Kuroda, Akiyoshi,Matsunaga, Hiroshi,Ikeda, Shushiro
-
p. 13919 - 13932
(2007/10/03)
-
- Substrate specificity in short-chain phospholipid analogs at the active site of human synovial phospholipase A2
-
The substrate specificity at the active site of recombinant human synovial fluid phospholipase A2 (hs-PLA2) was investigated by the preparation of a series of short-chain phospholipid analogs and measurement of their enzymatic hydrolysis at concentrations well below the critical micelle concentration. Substrates used in the study included 1,2-dihexanoylglycerophospholipids, 1,2-bis(alkanoylthio)glycerophospholipids, and 1-O-alkyl-2- (alkanoylthio)phospholipids. Turnover was observed for only a few of the 1,2- dihexanoylglycerophospholipids, and the rate of hydrolysis was very low, near the limit of detection of the assay. In contrast, selected 2-(alkanoylthio)- glycerophospholipids were hydrolyzed by hs-PLA2 at much higher rates at concentrations well below their critical micelle concentration (cmc). Thus, the 1,2-bis(hexanoylthio)glycerophosphatidylmethanol exhibits a k(cat)/K(M) = 1800 L mol-1 s-1. Over the calculated log P (cLogP) range of 3-9, cLogP and log(k(cat)/K(M)) were linearly related for compounds with straight-chain sn-1 and sn-2 substituents. At comparable cLogP's, the sn-1 ethers and thioesters were hydrolyzed at comparable rates. A negative charge in the phosphate head group was required for enzyme activity. Unsaturation, aromaticity, and branching in the sn-2 substituent reduce turnover dramatically. The same structural modifications in the sn-1 substituent have less effect on turnover. Certain of these substrates, e.g., 1,2- bis(hexanoylthio)glycerophosphatidylmethanol, may be useful in assaying for active site inhibitors of PLA2. The structure-activity relationships established here for substrates should serve as a reference for the structure-activity relationships of substrate-based inhibitors.
- Wheeler,Blanchard,Andrews,Fang,Gray-Nunez,Harris,Lambert,Mehrotra,Parks,Ray,Smalley Jr.
-
p. 4118 - 4129
(2007/10/02)
-
- Synthesis and thermotropic properties of macrocyclic lipids related to archaebacterial membranes
-
Macrocyclic phospholipids containing 32-44 ring atoms were synthesized by a route involving a high-temperature Glaser oxidation as the key step. These lipids are analogous to mammalian phospholipids except a single extra carboncarbon bond joins the chain termini. The new lipids offered, therefore, an opportunity to examine thermotropic properties of their membranes when the chains within a given molecule are unable to move independently of one another. It was concluded that chain "tethering" (a) raises the transition temperatures substantially for all but the shortest lipids, (b) lowers enthalpies of transition by, in part, reducing the number of gauche C-C linkages created during the melting process, and (c) lowers entropies of transition by impeding motional freedom within the liquid-crystalline phase. Molecular mechanics calculations on the macrocyclic lipids are described briefly.
- Menger,Chen,Brocchini,Hopkins,Hamilton
-
p. 6600 - 6608
(2007/10/02)
-
- Analogues of the dioxolanes dexoxadrol and etoxadrol as potential phencyclidine-like agents. Synthesis and structure-activity relationships
-
A series of dioxolane analogues based on dexoxadrol ((4S,6S)-2,2-diphenyl- 4-(2-piperidyl)-1,3-dioxolane) and etoxadrol ((2S,4S,6S)-2-ethyl-2-phenyl-4- (2-piperidyl)-1,3-dioxolane) were prepared and tested for their ability to displace [3H]TCP (1-[1-(2-thienyl)cyclohexyl]piperidine) from PCP (1-(1- phenylcyclohexyl)piperidine) binding sites in rat brain tissue homogenates. Qualitative structure-activity relationships within this series were explored through modifications of the three major structural units of dexoxadrol, the piperidine, 1,3-dioxolane, and aromatic rings of the molecule. N-Alkyl derivatives of dexoxadrol were found to be inactive, as were those analogues where the dioxolane ring was modified. Phenyl-substituted etoxadrol analogues were compared to similarly substituted PCP analogues and distinct differences were found in their structure-activity relationships suggesting that the aromatic rings in these two drug classes interact differently with the PCP binding sites. The replacement of the phenyl ring in etoxadrol by either a 2- or 3-thienyl ring led to compounds with affinity comparable to etoxadrol, and the replacement of the ethyl moiety on etoxadrol's dioxolane ring with propyl (7) or isopropyl (8) led to compounds which were more potent than etoxadrol or PCP. The most potent compound was (2S,4S,6S)-2-ethyl-2-(1- chlorophenyl)-4-(2-piperidyl)-1,3-dioxolane (11), where a chlorine moiety was placed in the ortho position in the aromatic ring of etoxadrol. Its potency was comparable with TCP in vitro.
- Thurkauf,Mattson,Richardson,Mirsadeghi,Ornstein,Harrison Jr.,Rice,Jacobson,Monn
-
p. 1323 - 1329
(2007/10/02)
-
- Glycerin derivative and its pharmacological use
-
A glycerin derivative having the following formula (I) or (I') and a pharmacologically acceptable salt thereof are useful to treat diseases caused by the platelet activating factor. STR1
- -
-
-
- SYNTHESIS OF AXIALLY DISSYMMETRIC 3,5-OCTADIENE FRAMEWORK WITH C2 CHIRALITY VIA PALLADIUM(II)-CATALYZED TWOFOLD SIGMATROPIC REARRANGEMENT
-
Palladium(II)-catalyzed sigmatropic rearrangement of (4R,5R)-4,5-(bisacetoxy)-1,8-(bisbenzyloxy)-2(E),6(E)-octadiene has proceeded convergently to give (2S,7S)-2,7-(bisacetoxy)-1,8-(bisbenzyloxy)-3(E),5(E)-octadiene, translating the original chirality completely to the migration termini, which constitutes a novel synthesis of optically pure 3,5-octadiene with C2 chirality.
- Saito, Seiki,Hamano, Shin-ichi,Moriyama, Hiroshi,Okada, Keiji,Moriwake, Toshio
-
p. 1157 - 1160
(2007/10/02)
-
- Synthesis of Glycerophosphonolipids Containing Aminoalkylphosphonic Acids
-
1,2-Di-O-octadecyl- and 1,2-di-O-hexadecanoyl-sn-glycerol 3-(2-aminoethyl)phosphonate (21) and (22) and the (3-aminopropyl)phosphonate analogues (23) and (24) were prepared with the aim of obtaining enzyme (lipase)-stable liposomes.New reactions were devised and classic methodologies were modified in order to transform D-mannitol (6) into optically pure 1,2-di-O-substituted sn-glycerols (12) and (13) (R=C18H37 and C15H31CO).Benzyloxycarbonylaminoalkylphosphonic acids (5a) and (5b) were then coupled with the glycerols by means of condensing reagents such as 2,4,6-triisopropylbenzenesulphonyl chloride.The resulting N-protected lipids were catalitically hydrogenated to furnish compounds (21)-(24) in overall yields of 10-20 percent from compound (6).
- Yamauchi, Kiyoshi,Une, Fumiyoshi,Tabata, Sachio,Kinoshita, Masayoshi
-
p. 765 - 770
(2007/10/02)
-
- Synthesis and antiherpetic activity of (S)-, (R)- and (±)-9-[(2,3-dihydroxy-1-propoxy)methyl]guanine, linear isomers of 2'-nor-2'-deoxyguanosine
-
Racemic 9-[2,3-dihydroxy-1-propoxy)methyl]guanine [(±)-iNDG], a new analogue of acyclovir (ACV) and a structural analogue of 2'-nor-2'-deoxyguanosine (2'NDG), was synthesized and found to inhibit the replication of herpes simplex virus types 1 (HSV-1) and 2 (HSV-2). Subsequently, its optical isomers, (R)- and (S)-iNDG, were prepared from chiral intermediates. The chloromethyl ethers of 1,2-di-O-benzyl-D- and -L-glycerol were made and reacted with tris(trimethylsilyl)guanine to give the 9-alkylated guanines, which were deprotected by catalytic hydrogenolysis. Against HSV-1 and HSV-2 in cell culture, (S)-iNDG was approximately 10- to 25-fold more active than the R enantiomer and had an ED50 comparable to those for ACV and 2'NDG. The inferior activity of (R)-iNDG paralleled the poor inhibition of viral DNA polymerase by its phosphorylation products. In mice infected intraperitoneally or orofacially with HSV-1 or intravaginally with HSV-2, (S)-9-[(2,3-dihydroxy-1-propoxy)methyl]guanine [(S)-iNDG] was less efficacious than 2'NDG but comparable to or more active than ACV.
- Ashton,Canning,Reynolds,Tolman,Karkas,Liou,Davies,DeWitt,Perry,Field
-
p. 926 - 933
(2007/10/02)
-
- Efficient Synthesis of (R)-(-)-γ-Benzyloxymethyl-γ-butyrolactone from (D)-(+)-Mannitol
-
Efficient synthesis of (R)-(-)-γ-benzyloxymethyl-γ-butyrolactone (10) has been developed using (D)-(+)-mannitol (1) as starting material.
- Takano, Seiichi,Goto, Emiko,Hirama, Michiyasu,Ogasawara, Kunio
-
p. 381 - 385
(2007/10/02)
-