Revisited Mechanistic Implications of the Joullié–Ugi Three-Component Reaction

The effect of the solvent on the diastereoselectivity of the Joullié–Ugi three-component reaction (JU-3CR) using an α-substituted five-membered cyclic imine is revisited. The <i>cis</i> and <i>trans</i> isomers were generated in toluene and HFIP, respectively. Hammett analysis of the JU-3CR suggests the presence of two reaction mechanisms

Development of the Carboxamide Protecting Group, 4-(<i>tert</i>-Butyldimethylsiloxy)-2-methoxybenzyl

The new carboxamide protecting group, 4-(<i>tert</i>-butyldimethylsiloxy)-2-methoxybenzyl (SiMB), has been developed. While this SiMB group can be removed using mild basic desilylation methods, it can also be deprotected under strongly acidic or oxidative conditions. An application of this group to simple carboxamide groups, as well as to more complex and acid-sensitive adenosine derivatives containing a cyclophane scaffold, was also demonstrated

Total Synthesis of Quinaldopeptin and Its Analogues

The first total synthesis of quinaldopeptin (<b>1</b>) was accomplished. Our approach to the synthesis of <b>1</b> includes the solid-phase peptide synthesis of the linear decapeptide <b>4</b> followed by macrocyclization and introduction of the quinoline chromophores <b>2</b> at a late stage of the synthesis. As for the preparation of <b>4</b>, a fragment coupling approach was applied considering the <i>C</i>2 symmetrical structure of <b>1</b>. Chromophore analogues <b>22</b> and <b>23</b> and desmethyl analogue <b>27</b> were also prepared in a manner similar to the synthesis of <b>1</b>. Synthetic <b>1</b> exhibits a strong cytotoxicity with the IC₅₀ value of 3.2 nM. On the other hand, the activity of <b>23</b> and <b>27</b> was largely reduced

Synthesis of <i>C</i>‑Glycosyl Pyrrolo[3,4‑<i>c</i>]carbazole-1,3(2<i>H</i>,6<i>H</i>)‑diones as a Scaffold for Check Point Kinase 1 Inhibitors

Indolocarbazole natural products are known to possess a variety of biological activities that hold promise as cancer chemotherapeutic agents. We newly designed <i>C</i>-glycosyl pyrrolo­[3,4-<i>c</i>]­carbazole-1,3­(2<i>H</i>,6<i>H</i>)-dione derivatives <b>7</b> and <b>8</b>, which are natural-product-like scaffolds. Compounds <b>7</b> and <b>8</b> were stereoselectively and efficiently synthesized using β-selective <i>C</i>-allylation, Heck reaction, and thermal 6π-electron cyclization/oxidative aromatization. Their potential as Chk1 inhibitors was investigated, and <b>7</b> and <b>8</b> exhibited an inhibitory activity with IC₅₀ values of 0.5–9.5 μM, which is good activity for scaffolds. The key intermediate <b>23</b> was obtained by five steps from d-ribose in 33% overall yield by this synthetic route, which would enable us to prepare a range of analogues in order to investigate further structure–activity relationship studies in the optimization process

Tris(azidoethyl)amine Hydrochloride; a Versatile Reagent for Synthesis of Functionalized Dumbbell Oligodeoxynucleotides

Triazole-cross-linked oligodeoxynucleotides were synthesized using the Cu(I) catalyzed alkyne–azide cycloaddition with tris(azidoethyl)amine hydrochloride and oligodeoxynucleotides possessing <i>N</i>-3-(propargyl)thymidine at both the 3′- and 5′-termini. Further installation of a functional molecule to the dumbbell oligodeoxynucleotides was achieved by utilizing the remaining azide group

Total Synthesis of Sandramycin and Its Analogues via a Multicomponent Assemblage

The total synthesis of sandramycin has been accomplished by using a Staudinger/aza-Wittig/diastereoselective Ugi three-component reaction sequence as a key step to obtain a linear pentadepsipeptide. Subsequent [5 + 5] coupling of the penptapeptide, macrolactamization, and introduction of the quinaldin chromophores afforded sandramycin. Dihydroxy and diacetoxy analogues were also prepared, and the cytotoxic activity of these analogues against a range of human cancer cell lines was evaluated

Carbacaprazamycins: Chemically Stable Analogues of the Caprazamycin Nucleoside Antibiotics

Carbacaprazamycins, which are chemically stable analogues of caprazamycins, were designed and synthesized. These analogues were active against drug-resistant bacterial pathogens such as methicillin-resistant <i>Staphylococcus aureus</i> and vancomycin-resistant enterococci, and their activities were comparable to those of the parent caprazamycins. The effect of treatment with carbacaprazamycin on morphological changes in <i>S. aureus</i> indicated that the mode of action was completely different from those of existing peptidoglycan inhibitors

Design, Synthesis, and Biological Activity of Isosyringolin A

Isosyringolin A, which is an isomer of the proteasome-inhibiting natural product syringolin A, was designed and synthesized to develop analogues that are step economical and synthetically accessible in a practical manner. It was revealed that isosyringolin A exhibited proteasome-inhibitory activity comparable to that of syringolin A and that its derivatization leads to great enhancement in its proteasome inhibitory activity as well as its cytotoxicity against human myeloma cells

PCR Amplification of 4′-ThioDNA Using 2′-Deoxy-4′-thionucleoside 5′-Triphosphates

2′-Deoxy-4′-thioribonucleic acid (4′-thioDNA) having a sulfur atom instead of an oxygen atom in the furanose ring has a nuclease resistance and hybridization ability higher than that of natural DNA. Despite its great potential for various biological applications, a long 4′-thioDNA having all four kinds of 2′-deoxy-4′-thionucleosides has not been reported. In this study, we describe systematic analysis of the incorporation of 2′-deoxy-4′-thionucleoside 5′-triphosphates (d<i>S</i>NTPs) using various DNA polymerases. We found that family B DNA polymerases, which do not have 3′→5′ exonuclease activity, could efficiently incorporate d<i>S</i>NTPs via single nucleotide insertion and primer extension. Moreover, 104-mer PCR product was obtained even under the conditions in the presence of all four kinds of d<i>S</i>NTPs when KOD Dash DNA polymerase was used. The resulting PCR product was converted into a natural dsDNA by using PCR with dNTPs, and sequencing of the natural dsDNA revealed that the PCR cycle successfully proceeded without losing the sequence information of the template. To the best of our knowledge, this is the first example of accurate PCR amplification of highly modified DNA in the presence of only unnatural dNTPs

The binding of DNA-G4, RNA-24, Cl-2-23 and CII-1-37 to varying concentration of human α-thrombin was determined by nitrocellulose filter partitioning as described in Materials and Methods

<p><b>Copyright information:</b></p><p>Taken from "New NTP analogs: the synthesis of 4′-thioUTP and 4′-thioCTP and their utility for SELEX"</p><p>Nucleic Acids Research 2005;33(9):2942-2951.</p><p>Published online 24 May 2005</p><p>PMCID:PMC1140078.</p><p>© The Author 2005. Published by Oxford University Press. All rights reserved</p