36326-38-2Relevant academic research and scientific papers
MONOBACTAM COMPOUNDS AND USE THEREFOR
-
, (2022/01/12)
Monobactam compounds and a use therefor. Specifically provided are chemical compounds represented by formula (I) or isomers, pharmaceutically acceptable salts, solvates, crystals, or prodrugs thereof, preparation methods therefor, pharmaceutical compositions containing said compounds, and a use of said compounds or compositions in treating bacterial infection. The present compounds feature excellent antibacterial activity, and have great hopes of becoming a therapeutic agent for bacterial infection.
Total Synthesis of a Mycolic Acid from Mycobacterium tuberculosis
Buter, Jeffrey,Fodran, Peter,Jayaraman, Dhineshkumar,Minnaard, Adriaan J.,Moody, D. Branch,Ocampo, Tonatiuh A.,Tahiri, Nabil,Van Rhijn, Ildiko,Witte, Martin D.
supporting information, p. 7555 - 7560 (2020/03/23)
In Mycobacterium tuberculosis, mycolic acids and their glycerol, glucose, and trehalose esters (“cord factor”) form the main part of the mycomembrane. Despite their first isolation almost a century ago, full stereochemical evaluation is lacking, as is a scalable synthesis required for accurate immunological, including vaccination, studies. Herein, we report an efficient, convergent, gram-scale synthesis of four stereo-isomers of a mycolic acid and its glucose ester. Binding to the antigen presenting protein CD1b and T cell activation studies are used to confirm the antigenicity of the synthetic material. The absolute stereochemistry of the syn-methoxy methyl moiety in natural material is evaluated by comparing its optical rotation with that of synthetic material.
Stereoselective synthesis and antiproliferative activity of the isomeric sphinganine analogues
?onková, Miroslava,Martinková, Miroslava,Gonda, Jozef,Jacková, Dominika,Pilátová, Martina Bago,Kupka, Daniel,Jáger, Dávid
, p. 76 - 85 (2018/12/11)
A flexible synthetic approach to biologically active sphingoid base-like compounds with a 3-amino-1,2-diol framework was achieved through a [3,3]-sigmatropic rearrangement and late stage olefin cross-metathesis as the key transformations. The stereochemistry of the newly created stereogenic centre was assigned via a single crystal X-ray analysis of the (4S,5R)-5-(hydroxymethyl)-4-vinyloxazolidine-2-thione. In order to rationalise the observed stereoselectivity of the aza-Claisen rearrangement, DFT calculations were carried out. The targeted isomeric sphingoid bases were screened in vitro for anticancer activity on a panel of seven human malignant cell lines. Cell viability experiments revealed that C17-homologues are more active than their C12 congeners.
Assignment of the relative and absolute stereochemistry of two novel epoxides using NMR and DFT-GIAO calculations
Moraes,Alvarenga,Demuner,Viana
, p. 109 - 115 (2018/05/03)
Considering the potential biological application of isobenzofuranones, especially as agrochemical defensives, two novel epoxides, (1aR,2R,2aR,5S,5aS,6S,6aS)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (9), and (1aS,2S,2aR,5S,5aS,6R,6aR)-5-(hydroxymethyl)hexahydro-2,6-methanooxireno[2,3-f]isobenzofuran-3(1aH)-one (10), were synthesized from the readily available D-mannitol in six steps. The multiplicities of the hydrogens located at the bridge of the bicycle are distinct for epoxides 9 and 10 due to W coupling, and this feature was employed to confirm the assignment of these nuclei. Besides analyses of the 2D NMR spectra, the assignments of the nuclei at the epoxide ring were also inferred from information obtained by theoretical calculations. The calculated 1H and 13C NMR chemical shifts for eight candidate structures were compared with the experimental chemical shifts of 9 and 10 by measuring the mean absolute errors (MAE) and by the DP4 statistical analysis. The structures and relative configurations of 9, and 10 were determined via NMR spectroscopy assisted with theoretical calculations. As consequence of the enantioselective syntheses starting from a natural polyol, the absolute configurations of the epoxides 9 and 10 were also defined.
PROCESS FOR THE PREPARATION OF [(1 S,2R)-3-[[(4-AMINOPHENYL)SULFONYL] (2-METHYLPROPYL)AMINO]-2-HYDROXY-1 -(PHENYLMETHYL)PROPYL]-CARBAMIC ACID (3R,3AS,6AR)HEXAHYDRO FURO[2,3-B]FURAN-3-YL ESTER AND ITS AMORPHOUS FORM
-
, (2017/04/21)
The present invention relates to an improved process for the preparation of [(1 S,2R)-3-[ [(4-aminophenyl)sulfonyl] (2-methylpropyl)amino]-2-hydroxy- 1 -(phenylmethyl)propyl] - carbamic acid (3R,3aS,6aR)hexahydrofuro[2,3-b]furan-3-yl ester compound of formula- 1 represented by the following structural formula:
Synthesis and evaluation of eight- and four-membered iminosugar analogues as inhibitors of testicular ceramide-specific glucosyltransferase, testicular β-glucosidase 2, and other glycosidases
Lee, Jae Chul,Francis, Subhashree,Dutta, Dinah,Gupta, Vijayalaxmi,Yang, Yan,Zhu, Jin-Yi,Tash, Joseph S.,Schoenbrunn, Ernst,Georg, Gunda I.
experimental part, p. 3082 - 3098 (2012/05/31)
Eight- and four-membered analogues of N-butyldeoxynojirimycin (NB-DNJ), a reversible male contraceptive in mice, were prepared and tested. A chiral pool approach was used for the synthesis of the target compounds. Key steps for the synthesis of the eight-membered analogues involve ring-closing metathesis and Sharpless asymmetric dihydroxylation and for the four-membered analogues Sharpless epoxidation, epoxide ring-opening (azide), and Mitsunobu reaction to form the four-membered ring. (3S,4R,5S,6R,7R)-1-Nonylazocane-3,4,5,6,7-pentaol (6) was moderately active against rat-derived ceramide-specific glucosyltransferase, and four of the other eight-membered analogues were weakly active against rat-derived β-glucosidase 2. Among the four-membered analogues, ((2R,3S,4S)-3-hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (25) displayed selective inhibitory activity against mouse-derived ceramide-specific glucosyltransferase and was about half as potent as NB-DNJ against the rat-derived enzyme. ((2S,4S)-3-Hydroxy-1-nonylazetidine-2,4-diyl)dimethanol (27) was found to be a selective inhibitor of β-glucosidase 2, with potency similar to NB-DNJ. Additional glycosidase assays were performed to identify potential other therapeutic applications. The eight-membered iminosugars exhibited specificity for almond-derived β-glucosidase, and the 1-nonylazetidine 25 inhibited α-glucosidase (Saccharomyces cerevisiae) with an IC50 of 600 nM and β-glucosidase (almond) with an IC50 of 20 μM. Only N-nonyl derivatives were active, emphasizing the importance of a long lipophilic side chain for inhibitory activity of the analogues studied.
Practical one-pot synthesis of protected l-glyceraldehyde derivatives
Stecko, Sebastian,Michalak, Micha,Stodulski, MacIej,Muchal, Lukasz,Parda, Kamil,Furman, Bartlomiej,Chmielewski, Marek
, p. 2695 - 2698 (2012/11/07)
A large-scale, simple, economic, and safe procedure for the preparation of l-glyceraldehyde acetonide under conditions, which allow its direct transformation (one-pot) into the desired products (acetylene, imine, nitrone, unsaturated ester) is reported. l-Glyceraldehyde acetonide is obtained from the corresponding ester, which is readily available from l-serine. Georg Thieme Verlag Stuttgart New York.
Total synthesis of branimycin: An evolutionary approach
Enev, Valentin S.,Felzmann, Wolfgang,Gromov, Alexey,Marchart, Stefan,Mulzer, Johann
, p. 9651 - 9668 (2012/09/21)
The first total synthesis of the macrolactone antibiotic branimycin (4) has been described. The key disconnection leads to a cis-dehydrodecalone core and a polyketide side chain which are connected via organometallic addition. The dehydrodecalone core was targeted via altogether five different approaches featuring various kinds of chiral elements and ring-closing methodology. In the end the most successful method starting from diepoxynaphthalene 109 was chosen to carry on with the synthesis. Thus the oxygen functions and carbon appendages were introduced via organometallic desymmetrization reactions to generate epoxy ketone 107, to which vinyl iodide 11 was added after conversion into the organolithium species. The synthesis was completed by introducing the ester side chain via Michael addition and subsequent macrolactonization. Competitive approach: The first total synthesis of the macrolactone antibiotic branimycin is described (see figure). The dehydrodecalin core was targeted via five competing approaches featuring various kinds of chiral elements and ring-closing methodology. In this "Darwinian" struggle the most successful route emerged and led to the completion of the synthesis. Copyright
Design, synthesis, and X-ray structure of substituted bis-tetrahydrofuran (bis-THF)-derived potent HIV-1 protease inhibitors
Ghosh, Arun K.,Martyr, Cuthbert D.,Steffey, Melinda,Wang, Yuan-Fang,Agniswamy, Johnson,Amano, Masayuki,Weber, Irene T.,Mitsuya, Hiroaki
body text, p. 298 - 302 (2011/06/21)
We investigated substituted bis-THF-derived HIV-1 protease inhibitors in order to enhance ligand-binding site interactions in the HIV-1 protease active site. In this context, we have carried out convenient syntheses of optically active bis-THF and C4-substituted bis-THF ligands using a [2,3]-sigmatropic rearrangement as the key step. The synthesis provided convenient access to a number of substituted bis-THF derivatives. Incorporation of these ligands led to a series of potent HIV-1 protease inhibitors. Inhibitor 23c turned out to be the most potent (Ki = 2.9 pM; IC50 = 2.4 nM) among the inhibitors. An X-ray structure of 23c-bound HIV-1 protease showed extensive interactions of the inhibitor with the protease active site, including a unique water-mediated hydrogen bond to the Gly-48 amide NH in the S2 site.
Enantioselective total synthesis of (-)-Clavosolide A and B
Son, Jung Beom,Kim, Si Nae,Kim, Na Yeong,Hwang, Min-Ho,Lee, Wonsun,Lee, Duck Hyung
scheme or table, p. 653 - 663 (2010/08/19)
Enantioselective total synthesis of (-)-clavosolide A and B was reported in full including the synthesis of proposed structure of (-)-clavosoldie A (1), revised structure of (-)-clavosoldie A (5), and revised structure of (-)-clavosoldie B (6). The relative and absolute stereochemistries of the natural products were confirmed unambiguously by comparing the optical rotation values and 1H and 13C NMR spectra of them.
