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ARKIVOC 2021 5;2021:97-109. Epub 2021 Apr 5.

Department of Chemistry; University of Pennsylvania; 231 South 34th Street; Philadelphia, Pennsylvania 19104-6323, USA.

Fluorescent amino acids are powerful biophysical tools as they can be used in structural or imaging studies of a given protein without significantly perturbing its native fold or function. Here, we have synthesized and characterized 7-(dimethylamino)acridon-2-ylalanine (Dad), a red-shifted derivative of the genetically-incorporable amino acid, acridon-2-ylalanine. Alkylation increases the quantum yield and fluorescence lifetime of Dad relative to a previously published amino acid, 7-aminoacridon-2-ylalanine (Aad). Read More

ARKIVOC 2020 2;2020(Pt 7):242-256. Epub 2020 Dec 2.

Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53211, USA.

Antinociceptive ligand HZ-166 is a GABA α2/α3 receptor subtype-selective potentiator. It has been shown to exhibit anxiolytic-like effects in rodent and rhesus monkeys, as well as reduced sedative/ataxic liabilities. In order to improve the metabolic stability of HZ-166, the ethyl ester moiety was bioisosterically replaced with 2,4-disubstituted oxazoles and oxazolines. Read More

ARKIVOC 2019;2019(1):1-17. Epub 2019 Mar 30.

Department of Chemistry, University of Minnesota Twin Cities, Minneapolis, Minnesota 55455, United States.

Allylic azides are underutilized in organic synthesis when compared to other organic azides or other allylic functionality. This is likely because allylic azides rearrange at room temperature, resulting in a potentially complex mixture of azides. This rearrangement has been termed the Winstein rearrangement. Read More

ARKIVOC 2018;2018(Pt II):252-279. Epub 2017 Dec 21.

Department of Chemistry & Biochemistry, The City College of New York, 160 Convent Avenue, New York, NY 10031, USA, and The Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY 10016, USA.

There has been increasing use of hypervalent iodine reagents in the field of nucleoside chemistry. Applications span: (a) synthesis of nucleoside analogues with sulfur and seleno sugar surrogates, (b) synthesis of unusual carbocyclic and ether ring-containing nucleosides, (c) introduction of sulfur and selenium into pyrimidine bases of nucleosides and analogues, (d) synthesis of isoxazole and isoxazoline ring-containing nucleoside analogues, (e) involvement of purine ring nitrogen atoms for remote C-H bond oxidation, and (f) metal-catalyzed and uncatalyzed synthesis of benzimidazolyl purine nucleoside analogues by intramolecular C-N bond formation. This review offers a perspective on developments involving the use of hypervalent iodine reagents in the field of nucleoside chemistry that have appeared in the literature in the 2003-2017 time frame. Read More

ARKIVOC 2018;2018(4):158-182. Epub 2018 Mar 11.

Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, Wisconsin 53201, United States.

A series of novel imidazobenzodiazepine analogs of the lead chiral ligand SH-053-2'F--CH (), an α2/α3/α5 (Bz)GABA (A)ergic receptor subtype selective ligand, which reversed PCP-induced prepulse inhibition (PPI) of acoustic startle, were synthesized. These chiral ()-CH ligands are targeted for the treatment of schizophrenia and depression. These new ligands were designed by modifying the liable ester functionality in to improve the metabolic stability, cytotoxicity, and activity as compared to . Read More

ARKIVOC 2018;2018:204-233. Epub 2018 Nov 26.

Department of Chemistry, 1101 University Avenue, Madison, WI 53706, U.S.A.

The prevalence of stereochemically complex amines in natural products, pharmaceuticals and other bioactive compounds, coupled with the challenges inherent in their preparation, has inspired our work to develop new and versatile methodologies for the synthesis of amine-containing stereotriads ('triads'). The key step is a highly chemo-, regio-, and stereoselective transition-metal catalyzed nitrene transfer reaction that transforms one of the cumulated double bonds of an allene precursor into a bicyclic methyleneaziridine intermediate. This account summarizes our strategies to rapidly elaborate such intermediates into stereochemically rich, densely functionalized amine triads, nitrogen heterocycles, aminated carbocycles and other useful synthetic building blocks. Read More

ARKIVOC 2018;2018(2):280-287. Epub 2018 Jan 28.

Department of Chemistry, University of South Florida, Tampa, FL 33620, USA.

Herein, we describe the synthesis of a novel bis-1,2,3-triazole ligand which contains an internal N-alkylated 2,2'-bipyrrolidine linker. By using simple starting materials, the ligand could be generated in good yield through several synthetic steps. To investigate the potential for the application of this ligand in transition metal catalysis, we generated a bis-Au(I) complex in nearly quantitative yield and examined its reactivity in the context of alkyne hydration. Read More

ARKIVOC 2018;2018(4):132-138. Epub 2018 Mar 28.

Department of Chemistry, Burke Laboratory, Dartmouth College, Hanover, NH 03755.

Alkoxide-directed metal-centered intermolecular [2+2+2] annulation is shown to chemo-, regio-, and stereoselectively engage two polyunsaturated substrate in productive cyclization chemistry. This annulation process is unique in the field, revealing that it is possible to selectively engage three of five π-systems residing in the coupling partners in initial [2+2+2] reaction, and demonstrating that one of the two remaining π-systems (the TMS-alkyne) can ultimately serve to simply generate a new metallacyclopentene of great potential value in additional metallacycle-mediated coupling chemistry. Read More

ARKIVOC 2015;2015(5):164-175. Epub 2015 Apr 5.

Department of Chemistry, Faculty of Science, King Abdulaziz University, P.O. Box 80203, Jeddah 21589, Saudi Arabia; Department of Chemistry, Faculty of Science, Damietta University, Damietta, Egypt.

Bioassay-guided fractionation of the extract of Jamaican marine sponge sp. followed by preparative TLC and HPLC yielded several known methyl ester cyclic peroxides (), known plakortides (), known bicyclic lactone () and new cyclic peroxide acids (). The chemical structures were elucidated by extensive interpretation of their spectroscopic data. Read More

ARKIVOC 2016;2016(1):276-306. Epub 2016 Jun 21.

Department of Chemistry and Biochemistry, New Mexico State University, Las Cruces, New Mexico, 88003, USA.

This account describes the historical development of the coupling of γ,δ-unsaturated Fischer carbene complexes and -alkynylbenzaldehydes, which directly affords hydrophenanthrene ring systems in a process where each reactant contributes five carbons to the newly-formed bicyclo[4.4.0]decane ring system. Read More

ARKIVOC 2014;2014(1):127-141

This Highlight accounts for a recent phenomenon in which a series of novel ynamide structural analogues have emerged and caught the attention of the synthetic community. Preparations and reactions of these ynamide variants are delineated here to demonstrate their accessibility as well as their reactivity. This Highlight should help reveal that these unique N-containing alkynes can become highly versatile building blocks in organic syntheses. Read More

ARKIVOC 2011 Jan;2011(Pt 5):167-179

Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, U.S.A.

Asymmetric alkylation of enantiomeric tetrahydroisoquinolyl oxazolines was achieved with 96-97% diastereoselectivity. Removal of the oxazoline chiral auxiliary and further transformations provide a straightforward synthesis of the two synthetic intermediates that were previously synthesized by resolution, and which comprise a formal synthesis of berbamunine by Ullman coupling. Read More

ARKIVOC 2010 Jul;2010:251-262

Noncovalent interactions play an essential role in biological and chemical processes. In the main chain of common protein secondary structures, the lone pair (n) of a carbonyl oxygen is delocalized into the antibonding orbital (π*) of the subsequent carbonyl group. Herein, experimental and computational data reveal that this n→π* interaction can be attenuated by the inductive electron withdrawal of one or two α-fluoro groups in the donor. Read More

ARKIVOC 2010 Jun;2010:175-188

Fox Chase Chemical Diversity Center, Inc., Pennsylvania Center for Drug Discovery, Pennsylvania Biotechnology Center, Doylestown, PA 18902 USA.

Porphobilinogen synthase (PBGS) catalyzes the first common step in the biosynthesis of the essential heme, chlorophyll and vitamin B(12) heme pigments. PBGS activity is regulated by assembly state, with certain oligomers exhibiting biological activity and others either partially or completely inactive, affording an innovative means of allosteric drug action. Pseudomonas aeruginosa PBGS is functionally active as an octamer, and inactive as a dimer. Read More

ARKIVOC 2011;2011(7):221-226. Epub 2011 Feb 27.

Department of Chemistry and Biochemistry, University of Notre Dame, Notre Dame, IN 46556, USA.

A series of 4-[(triazolyl)methoxy]phenyl analogs of the phenoxyphenyl-substituted thiirane SB-3CT was evaluated for its ability to inhibit gelatinases, members of the matrix metalloproteinase family of enzymes. The triazole segment of these inhibitors was assembled using the Meldal-Sharpless copper-catalyzed Huisgen dipolar cycloaddition of an azide and a terminal alkyne. While these triazole derivatives possessed fair activity as gelatinase inhibitors, an intermediate used in the dipolar cycloaddition, 4-(propargyloxy)phenyl derivative , showed very good activity (>50% inhibitory activity following a 3 h pre-incubation of at a concentration of 3 μM) as an inhibitor of human matrix metalloproteinase-2. Read More

ARKIVOC 2011;2011(5):34-44. Epub 2010 Oct 31.

Department of Chemistry, Connecticut College, 270 Mohegan Avenue, New London, CT 06320,

This article describes the development of microwave-assisted oxyanionic 5-exo-dig cyclization-Claisen rearrangement sequence as a convenient "one-pot" route to a variety of seven-membered carbocyclic ring systems. This process was used as the key transformation for the construction of several natural products, including frondosins A, B, and C. Read More

ARKIVOC 2010 Dec;2011(5):76-91

A convenient method for construction of polycyclic fused nitrogen-containing heterocycles has been developed. The methodology involves palladium-catalyzed intermolecular carbopalladation-annulation cascade reaction of haloaryl heterocyclic derivatives with different alkynes under relatively mild reaction conditions. Thus, the palladium-catalyzed cascade cyclization of bromophenyl derivatives of indolizine and indole with alkynes afforded tetracycles, possessing a newly formed fused six-membered ring. Read More

ARKIVOC 2009 May;2010(5):5-16

In order to investigate the relationship between depth within membranes of singlet oxygen generation and effectiveness of photodynamic therapy of tumors, analogs of protoporphyrin-IX 1 bearing five 4 and seven 5 carbon atoms (in place of the 3-carbon atom chain in 1) were synthesized from monopyrrole precursors. Read More

ARKIVOC 2004 May;i:101-109

Fluorous Technologies, Inc. University of Pittsburgh Applied Research Center, 970 William Pitt Way Pittsburgh, PA 15238, USA E-Mail:

Fluorous mixture synthesis (FMS) is a newly developed highly-efficient solution-phase technology. A set of substrates attached to homologous fluorous tags is mixed and taken through a sequence of organic reactions. The final mixtures are demixed by fluorous HPLC and detagged to give individually pure final products. Read More

ARKIVOC 2005 Aug;2005(6):339-344

2,3-O-Carbonate protected rhamnopyranosides with both the α- and β-anomeric configuration are shown crystallographically to have ring conformations that differ significantly from the chair and which approach the (o)H(5) half-chair. This distortion, which is greatest in the α-anomer, provides a basis for the α-selectivity of 2,3-O carbonate protected manno- and rhamnopyranosyl donors as well as the conformationally related 2,3-O-alkylidene derivatives, in homogeneous solution phase glycosylation reactions. Read More

ARKIVOC 2007;2007(viii):49-57

An improved synthesis for the (Z)-14-methyl-9-pentadecenoic acid was developed based on the appropriate use of (trimethylsilyl)acetylene as the key reagent in the synthesis. The reported synthesis started with commercially available 8-bromo-1-octanol and furnished the desired acid in seven steps and in a 16% overall yield, a significant improvement over the previous reported synthesis for this fatty acid. The synthesis reported herein afforded sufficient amounts to study the acid topoisomerase I inhibitory potential and it was found that the title acid inhibits the human placenta DNA topoisomerase I enzyme at concentrations of 500 μM. Read More