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Indoles and Biindoles: Synthesis of Powerful Tools for Pharmaceutical and Materials Sciences
Get PDFPart 1: synthesis of indoles as potential bioactive compounds
Indole and related derivatives play a strong relevant role in heterocyclic chemistry. They are diffused in a
huge array of different natural products[1], many of them with intriguing biological activity.[2] Other
applications spread uncountable fields: material science, fragrances, agrochemicals, pigments and dyes and
many more.[3] It’s not surprising then that many efforts are made by organic chemists to find not only
synthetic methods to achieve indole fragments but also new functionalization protocols to afford with ease
complex targets.
Recently, Penoni group afforded a novel regioselective indole synthesis via annulation of variously
substituted nitrosoarenes and alkynes[4,5] (Figure 1). Main feature of this reaction is possibility to directly
prepare N-hydroxyindoles derivatives, when 4-nitronitrosobenzene is employed as reaction partner. High
efficiency on nitrosoarene-alkyne cycloaddition was noticed by trapping the formed unstable N-OH indole
product by methylation or interception with other electrophiles. Concerning other alkyne reactions with
other substituted nitrosobenzenes, indoles were detected as products; this feature was exploited to prepare
marine alkaloids meridianins and some modified aminoacids[6] (Figure 1). Reaction is supposed to pass
through a radical mechanism[7]
.
Figure 1: annulation reaction between alkynes and nitrosoarenes
3-Acylindoles(e.g. pravadoline, SCB01A, BPR0L075) are known to be bioactive compounds and recent studies
highlighted their interesting properties[8] and various synthetic approaches[9]. However, not many
indolization protocols are known to afford directly 3-acylindoles starting from easily available reactants.
Research topic was therefore focused on applying and optimizing nitrosoarene-alkyne one pot annulation
2
approach for the preparation of highly functionalizable compounds and/or biologically active products having
the 3-aroylindole fragment (Figure 2). Noticeably, after careful reaction optimization, unprotected Nhydroxy-3-aroylindoles were regioselectively detected as main products in most cases and recovered as
perfectly stable solid after precipitation with no need of protecting groups[10–12]
. Internal alkynes gave poor
reactivity.
Figure 2: annulation reaction between alkynones and nitrosoarenes.
Interestingly, reaction between 4-nitronitrosobenzene and 3-bromo-1-phenylprop-2-yn-1-one gave
regioselectively a 2-brominated indole compound. It is set as an objective for the near future a wide substrate
scope for synthesis of different 2-brominated indoles (Figure 3). Studies of reactivity of the latter compounds
towards classical cross coupling reactions is expected as well (Figure 3).
Figure 3: synthesis of a N-hydroxy-3-aroyl-2-bromo-indole (left); reactivity of the latter to classic cross
coupling reactions (right).
Part 2: synthesis of new organic semiconductors based on 2,2’- and 3,3’- biindole backbone
3
Inherently chiral materials based on 2,2’-biindole are characterized by an atropoisomeric backbone of two
2,2’ interconnected indole rings bearing 3,3’ substituents usually constituted by 2,2’-bitiophene units(Ind2T4,
Figure 4). Those substituents play the double role of hindering rotation around the interannular bond and
endowing system with specific properties. Main application of inherently chiral 2,2’-biindoles is as starting
materials to obtain enantiopure oligomeric selectors in chiral electrochemistry[13]
. Monomer oligomerization
is usually performed in electrochemical cell by many repeating anodic voltametric cycles to afford an
oligomeric coating directly on working electrode. Our interest in the chemistry of indoles led us to explore
the opportunity to get some analogous structure by structural modification of 3,3’-substituents. Introduction
of a π spacer (Ind2Ph2T4, Ind2T6, Figure 4) was performed to study its influence on chiral properties of resulting
oligomers, whilst introduction of a benzochalchogenodiazole subunit allows to achieve a donor-acceptor
moiety with interesting optical properties (Ind2BTD2T4, Ind2BSeD2T4, Figure 4).
Figure 4: enantiomers of Ind2T4 (left); target 2,2’-biindoles (right). R = alkyl.
Key core for synthesis of these compounds is a Larock-type 5-endo-dig double indole ring closure starting
from compound 1 (Scheme 1), as published by Abbiati in 2006[14]. This protocol shows good versatility as by
variation of aryl- or heteroaryl halide reaction partner is possible to prepare different 3,3’-diaryl/heteroaryl
2,2’-biindoles although in good to mediocre yield. Only racemate compounds are afforded due to lack of any
chiral catalyst. Subsequent nitrogen alkylation step is fundamental to ensure good solubility for processing.
Scheme 1: synthesis of 2,2’-biindoles starting from 1 and an aryl/heteroaryl halide.
4
All new compounds have been deeply characterized either monomeric or oligomeric. Separation of Ind2Ph2T4,
Ind2T6 in their two enantiomers was performed through semipreparative chiral HPLC, as up to now synthetic
method allows only to afford targets as racemate mixtures. After electrodeposition, Ind2Ph2T4 and Ind2T6
enantiopure oligomeric films showed great enantioselectivity towards both enantiomers of a chiral
ferrocenylamine (Figure 5).
Figure 5: cyclic voltammetry graphs showing different oxidation peaks for enantiopure oligo N-Pr-Ind2Ph2T4
(left) and N-Pr-Ind2T6 (right) towards two enantiomers of a chiral ferrocenylamine (bottom).
Concerning Ind2BTD2T4 and Ind2BSeD2T4, full characterization of monomers and electroactive films has been
carried out. Enantiorecognition tests are planned for next future.
Since Larock-type ring closure reaction has been proved very useful although mediocre yielding, a new and
more performant synthetic plan to afford Ind2T4 has been optimized (Scheme 2). Key step is high yield SuzukiMiyaura cross coupling reaction starting from compound 5. Future developments concern on use of different
boronic pinacol esters to afford Ind2Ph2T4, Ind2T6, Ind2BTD2T4 and Ind2BSeD2T4 in better yields as well.
5
Scheme 2: synthesis of Ind2T4 passing through a Suzuki cross coupling step.
Structural analogue 2,2’-diheteroaryl-3,3’-biindole 3,3’-Ind2T4 (Figure 6) was synthetized as well with the aim
to investigate its ability as chiral selectors. Unfortunately, when trying to separate them with chiral HPLC,
enantiomers peaks coalescence was noticed even at room temperature, suggesting configurational
instability.
Figure 6: synthesis of 3,3’-Ind2T4 (up); chiral HPLC profiles at different temperatures (bottom).
Computational studies indicated possibility to achieve configurational stability for 3,3’-biindoles by nitrogen
alkylation with very bulky tertbutyl group. Experiments in this direction are currently ongoing.
References:
[1] R. J. Sundberg, The Chemistry of Indoles, New York, 1970.
[2] V. Sharma, P. Kumar, D. Pathak, J. Heterocycl. Chem. 2010, 47, 491–502.
[3] T. C. Barden, Peptides 2011, 26, 31–46.
[4] A. Penoni, K. M. Nicholas, Chem. Commun. 2002, 2, 484–485.
[5] A. Penoni, J. Volkmann, K. M. Nicholas, Org. Lett. 2002, 4, 699–701.
[6] F. Tibiletti, M. Simonetti, K. M. Nicholas, G. Palmisano, M. Parravicini, F. Imbesi, S. Tollari, A. Penoni,
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Tetrahedron 2010, 66, 1280–1288.
[7] A. Penoni, G. Palmisano, Y. Zhao, K. N. Houk, J. Volkman, K. M. Nicholas, J. Am. Chem. Soc. 2009,
131, 653–661.
[8] D. G. Zhao, J. Chen, Y. R. Du, Y. Y. Ma, Y. X. Chen, K. Gao, B. R. Hu, J. Med. Chem. 2013, 56, 1467–
1477.
[9] S. J. Yao, Z. H. Ren, Z. H. Guan, Tetrahedron Lett. 2016, 57, 3892–3901.
[10] G. Ieronimo, G. Palmisano, A. Maspero, A. Marzorati, L. Scapinello, N. Masciocchi, G. Cravotto, A.
Barge, M. Simonetti, K. L. Ameta, et al., Org. Biomol. Chem. 2018, 16, 6853–6859.
[11] L. Scapinello, A. Maspero, S. Tollari, G. Palmisano, K. M. Nicholas, A. Penoni, J. Vis. Exp. 2020, 155, 1–
12.
[12] L. Scapinello, F. Vavassori, G. Ieronimo, K. L. Ameta, G. Cravotto, M. Simonetti, S. Tollari, G.
Palmisano, A. Maspero, K. M. Nicholas, et al., Manuscript in Preparation, 2020.
[13] S. Arnaboldi, T. Benincori, A. Penoni, L. Vaghi, R. Cirilli, S. Abbate, G. Longhi, G. Mazzeo, S. Grecchi,
M. Panigati, et al., Chem. Sci. 2019, 10, 2708–2717.
[14] G. Abbiati, A. Arcadi, E. Beccalli, G. Bianchi, F. Marinelli, E. Rossi, Tetrahedron 2006, 62, 3033–303
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
Author Under Sail The Imagination of Jack London, 1893-1902
No full textIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Intro -- Title Page -- Copyright Page -- Dedication -- Contents -- Acknowledgments -- Introduction -- 1. Spirit Truth -- 2. From Absorption to Theatricality and Back Again -- 3. "I Will Build a New Present" -- 4. Sons as Authors -- 5. Fathers as Publishers -- 6. The Daughter as Author -- 7. Lovers as Authors -- 8. At Sea with the Family -- 9. Yellow News, Yellow Stories -- 10. The Return Home -- Notes -- Bibliography -- Index -- About Jay WilliamsIn Author Under Sail, Jay Williams offers the first complete literary biography of Jack London as a professional writer engaged in the labor of writing. It examines the authorial imagination in London's work, the use of imagination in both his fiction and nonfiction, and the ways he defined imagination in the creative process in his business dealings with his publishers, editors, and agents. In this first volume of a two-volume biography, Williams traverses the years 1893 to 1902, from London's "Story of a Typhoon" to The People of the Abyss. The Jack London who emerges in the pages of Author Under Sail is a writer whose partnership with publishers, most notably his productive alliance with George Brett of Macmillan, was one of the most formative in American literary history. London pioneered many author models during the heyday of realism and naturalism, blurring the boundaries of these popular genres by focusing on absorption and theatricality and the representation of the seen and unseen. London created an impassioned, sincere, and extremely personal realism unlike that of other American writers of the time. Author Under Sail is a literary tour de force that reveals the full range of London as writer, creative citizen, and entrepreneur at the same time it sheds light on the maverick side of machine-age literature.Description based on publisher supplied metadata and other sources.Electronic reproduction. Ann Arbor, Michigan : ProQuest Ebook Central, YYYY. Available via World Wide Web. Access may be limited to ProQuest Ebook Central affiliated libraries
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