(+)-(1R,4S)-4-[(9-Fluorenylmethoxycarbonyl)amino]cyclopent-2-ene-1-carboxylic acid

Phosphorylation and dephosphorylation of splicing factors play a key role in pre-mRNA splicing events, and cantharidin and norcantharidin analogs inhibit protein phosphatase-1 (PP1) and change alternative pre-mRNA splicing. Targeted inhibitors capable of selectively inhibiting PP-1 could promote exon 7 inclusion in the survival-of-motorneuron-2 gene (SMN2) and shift the proportion of SMN2 protein from a dysfunctional to a functional form. As a prelude to the development of norcantharidin-tethered oligonucleotide inhibitors, the synthesis a norcantharidin-tethered guanosine was developed in which a suitable tether prevented the undesired cyclization of norcantharidin monoamides to imides and possessed a secondary amine terminus suited to the synthesis of oligonucleotides analogs. Application of this methodology led to the synthesis of a diastereomeric mixture of norcantharidin-tethered guanosines, namely bisammonium (1R,2S,3R,4S)- and (1S,2R,3S,4R)-3-((4-(2-(((((2R,3R,4R,5R)-5-(2-amino-6-oxo-1,6-dihydro-9H-purin-9-yl)-2-(hydroxymethyl)-4-methoxytetrahydrofuran-3-yl)oxy)oxidophosphoryl)oxy)ethyl)-phenethyl)(methyl)carbamoyl)-7-oxabicyclo[2.

The natural nucleoside antibiotic, bredinin, exhibits antiviral and other biological activities. While various nucleosides related to bredinin have been synthesized, its carbocyclic analog has remained unknown. Synthesis of this heretofore unknown analog of bredinin is described. The key precursor, (3aS,4R,6R,6aR)-6-((methoxy-methoxy)methyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-amine (5), was prepared from the commercially available compound, (1R,4S)-2-azabicyclo[2.2.1] hept-5-en-3-one (4). Our initial approach used intermediate 6, derived in three transformations from 5, for the key photolytic step to produce the desired ring-opened precursor to the target compound. This photochemical transformation was unsuccessful. However, an appropriately protected and related precursor was synthesized from 5 through the following side-chain functional group transformations: elaboration of the amino group through malonyl ester formation, oximation at the central carbon, conversion of ester to amide and catalytic reduction of the oxime group.

Various column chromatography, such as silica gel, Sephadex LH-20, ODS, and semi-preparative HPLC was used to isolate and purify the chemical constituents from Cinnamomum cassia. The structures were determined on the basis of NMR and MS spectral data analysis, together with the comparison with literature data. Fifteen compounds were isolated from the 85% aqueous ethanol extract of C. cassia, and their structures were identified as (2R, 3R)-5,7,3',4'-tetramethoxyflavan-3-ol( 1), (2R, 3R)-5,7-dimethoxy-3',4'-methylenedioxyflavan-3-ol (2), coumarin (3), cinnamic acid (4), (E)-2-hydroxy-phenylpropionic acid cinnamoyl ester (5), 3, 3', 4, 4'-tetrahydroxy biphenyl (6), methylstictic acid (7), epi-boscialin (8), (1R,2S,3S,4S)-2,3-epoxy-1, 4-dihydroxy-5-methyl-5-cyelohexene (9), 4,5-dihydroxy-3-methyl cyclohex-2-enone (10), cis-4-hydroxymellein (11), and 2-hydroxy-4-methoxyl-cinnamaldehyde (12). Compounds 5-11 were obtained from this genus plants for the first time.

Serogroup A of Neisseria meningitidis is the organism responsible for causing epidemic diseases in developing countries by a pilus-mediated adhesion to human brain endothelial cells. Type IV pilus assembly protein (PilF) associated with bacterial adhesion, aggregation, invasion, host cell signaling, surface motility, and natural transformation can be considered as a candidate for effective anti-meningococcal drug development. Since the crystal structure of PilF was not available, in the present study, it was modeled after the Z2491 strain (CAM09255.1) using crystal structure of chain A of Vibrio cholerae putative Ntpase EpsE (Protein Data Bank (PDB) ID: 1P9R) and then we based this analysis on sequence comparisons and structural similarity using in silico methods and docking processes, to design a suitable inhibitor molecule. The ligand 3-{(4S)-5-{[(1R)-1-cyclohexylethyl]amino}-4-[(5S)-5-(prop-2-en-1-yl) cyclopent-1-en-1-yl]-1,4-dihydro-7H-pyrrolo[2,3-d] pyrimidin-7-yl}-1,2-dideoxy-b-L-erythro-hex-1-en-3-ulofuranosyl binds to the protein with a binding energy of -8.