Bibliometric Study of Microwave-Assisted Synthesis of Flavanone Derivatives

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INTRODUCTION
Flavanones are a class of flavonoid compounds, a subclass of polyphenolic compounds found in various plants.Flavanones are characterized by their chemical structure, consisting of a 15-carbon skeleton with a ketone (carbonyl) group at the C4 position.They are derived from flavonoids by removing a double bond in the C2-C3 position of the flavonoid structure 1 .Flavanones are known for their antioxidant properties and are commonly found in various fruits and vegetables.Citrus fruits, such as oranges, lemons, and grapefruits, are prosperous sources of flavanones 2 .Some well-known flavanones found include pinostrobin, hesperetin, or naringenin.These compounds have been studied for their potential health benefits, including their role in reducing oxidative stress, inflammation, and their potential to support cardiovascular health 3 .Flavanones are also being investigated for their anti-cancer and anti-inflammatory properties 4 .Obtaining derivatives of flavanones typically involves modifying the parent organic molecule to introduce specific functional groups or structural changes.Derivatization is a common technique in organic chemistry used for various purposes, such as enhancing the compound's stability, reactivity, or analytical properties.It's important to note that the specific methods and reagents used to obtain organic derivatives can vary widely depending on the structure of the original compound and the desired modification.Safety precautions, proper lab techniques, and knowledge of organic chemistry principles are essential when working with organic compounds and their derivatives 5 .One of the most advanced, innovative, and environmentally friendly ways to obtain flavanone derivatives is to utilize microwaves using a microwave.Using a microwave can not only save material usage but can also shorten reaction time 6 .For example, our previous research 7 obtained prenyl derivatives from pinostrobin, a type of flavanone isolated from Boesenbergia pandurata, with a yield of 96% in 30 minutes using microwave assistance, which was proven to show anti-breast cancer activity 4-5 times better than pinostrobin.Therefore, microwave-assisted synthesis of flavanone derivatives is a feasible strategy for discovering new lead compounds with various pharmacological activities.However, no research exclusively reviews previous studies regarding the use of this method for flavanone derivatives.Therefore, this brief study aims to describe research related to the microwave-assisted synthesis of flavanone derivatives using a bibliometric approach

Materials
The software used to visualize the analysis results was VOSViewer 1.6.19(https://www.vosviewer.com/)from the Center for Science and Technology Studies, Leiden University.All analyzed articles were obtained from the Scopus database (https://www.scopus.com/sources.uri)on June 30 th , 2023.In this study, access to Scopus was provided by Universitas Airlangga, Surabaya, Indonesia.

Methods
The approach used was bibliometric analysis with the Scopus database.Search keywords were made in one search level consisting of three keywords.Apart from analyzing articles and journals, analysis was also carried out on the authors and the researchers' countries of origin.This bibliometric analysis provides an overview of research developments that have been reported for this scope and information about potential cooperation partners, including appropriate scientific journals to publish related research reports.This study adopted a method as reported by our previous research 8 as follows:

Determination of search keywords
In this study, the keywords used consist of one level, which consists of three keywords.The first keyword was the method used: "microwave-assisted OR microwave".The use of the 'OR' operator is indicated because of the probability of using other terms by the authors, so the term 'microwave' is used, which is more general.The second keyword was "synthesis" as the target carried out, while the third keyword was "flavanone" as the object studied.The criteria chosen for these keywords were the article's title, abstract, and keywords, assuming that articles that specifically address this topic must contain keywords specified in one of the three criteria.

Initial search results
Search results by keyword were presented as a whole in the Scopus database.Data collection of a number of Scopus documents is carried out without any restrictions, and no metadata is downloaded.In total, 34 documents contained titles, abstracts, or keywords containing the three previous search keywords.

Refinement of search results
The initial search results obtained were filtered based on several categories.Several parameters that could be limited in the Scopus database include access type, year of publication, author's name, subject area, document type, publication stage, source title, keywords, affiliation, funding sponsor, country, source type, and language.In this study, these parameters were not restricted to obtaining comprehensive results, except for the type of sources limited to journals.This limitation is made with the assumption that other types of sources, such as books, book series, and book chapters, contain tertiary information that is already available in journal articles.From the limitations, 33 relevant research articles were obtained for further analysis.

Compile preliminary data statistics
The filtered data was then downloaded in CSV format.Exported information includes citations, bibliography, abstract and keywords, funding details, and other information.

Data analysis
Bibliometric analysis of the downloaded data was performed and visualized using VOSviewer 1.6.19.As in our previous study, the parameters analyzed consisted of publications and citation structures, authors and co-authorship relations, and country of study location.

Publications and citation structures
Of the 33 published documents in Scopus Indexed Journals obtained based on searches, the most publications occurred during 2012 with five documents.The oldest publication was reported in 1999, and as of 2023, there are two publications on the topic.However, of the 33 articles, six were published in four journals that are no longer indexed by Scopus.Still, discontinued status applies to journals and articles published after the year of determination, while the articles analyzed were published earlier so the six articles are still used in the analysis.The article's complete results from the search results for these keywords were presented in Table I.Apart from authorship, data collection and analysis are conducted at the journal and publisher where the article is published.Analysis was carried out on these keyword combinations, and the results showed that 26 journals and 16 publishers published articles with these keyword combinations.Most articles were published in three journals: Chemistry of Heterocyclic Compounds (Springer Nature), Oriental Journal of Chemistry (Scientific Publishers), and Tetrahedron Letters (Elsevier), each with three articles.Meanwhile, the publishers with the most journals are Elsevier and Bentham, each with four journals.However, more articles are published in Elsevier journals than Bentham (6 versus 5).Nevertheless, considering the number of citations of published papers, publishing an article in the Journal of Organic Chemistry (American Chemical Society) is advantageous because it shows the highest chance of obtaining multiple citations (86 citations from 1 article) Complete data is presented in Table II.Further analysis based on keywords from each article shows exciting results, with several keywords with prominent link strength outside the search keywords (Microwave-assisted OR Microwave, Synthesis, and Flavanone).The keyword 'flavonoids' shows the highest occurrences (18) and link strength (300).However, 'microwave' and 'microwave-assisted' only showed 5 and 1 occurrences and 94 and 17 link strengths, respectively.The most popular keyword related to microwave technique is 'microwave irradiation' with 17 occurrences and 277 link strengths.In other words, the term 'microwave irradiation' seems more popular than 'microwave-assisted'. Another interesting point is that all the lead compounds used are written using IUPAC names, none of which are written in the title, abstract, and keywords using the trivial name of the compound.In addition, an analysis of the various lead compounds also showed that most of the well-known flavanones, such as pinostrobin, pinocembrin, or hesperetin, did not appear in search terms.Naringenin (in 6-prenylnaringenin or 8-prenylnaringenin) and sanggenol F are the only well-known flavanones that appear.Moreover, most authors focus on synthesizing flavanone compounds with starting materials such as chalcone rather than synthesizing existing flavanones.Even if there is, the majority use reflux method, as reported by Sinyeue et al 9 .Thus, the microwave-assisted synthesis of flavanone derivatives has been shown to offer a tremendous novelty opportunity due to the lack of previous studies, at least those published in Scopus-indexed journals, as shown in Figure 1.

Authors and co-authorship relations
Author institutional analysis with the Scopus database was not carried out due to inconsistent institutional writing due to non-harmonized institutional indexation on Scopus 8 .Instead, the analysis was performed on the authors and their agencies only.The analysis was performed based on the citation results of the entire document because these parameters can diversify each author instead of a direct author analysis (which only counts one author per article).The analysis results show that 13 authors show link strength above 500, but only six have citations above 10.The six authors were then identified with the most significant influence on the topics studied, especially those published in Scopus-indexed journals.The author with the most citations (26) is Rajender S. Varma from Technická Univerzita v Liberci, Czech Republic, with 758 link strength and last published an article on the related topic in 2007, indicating that this researcher is the most considered regarding this topic.However, the author with the most documents is Dongamanti Ashok from Osmania University, India, with five documents that were last published in 2019, as shown in Figure 2. Thus, these two researchers deserve to be role models for research on microwave-assisted synthesis of flavanone derivatives 10 .

Country of study location
Finally, the analysis is carried out on the country of origin of the researcher, or in other words, the country of origin of the researcher's institution.The 33 documents were published by researchers from 12 countries, both individually and in collaboration between countries, as shown in Figure 3.There is only one document produced by cross-country collaboration: between the US (US Environmental Protection Agency) and Hungary (University of Debrecen and University of Kaposvár).India produced the most articles on this topic, with 13 documents, followed by the US and Portugal, with four documents each.Of the 13 documents, six were published by researchers from Osmania University, Hyderabad, the same affiliate as Dongamanti Ashok, the researcher with the most documents on the topic.In other words, the institution is the global epicenter of research on microwave-assisted synthesis of flavanone derivatives.

Table I .
Articles on Scopus with the keywords "Microwave-assisted OR Microwave", "Synthesis", and "Flavanone".Articles in red indicate discontinued status in the Scopus database

Table II .
Comparison of each journal and publisher with the keywords "Microwave-assisted OR Microwave", "Synthesis", and "Flavanone".Journals in red indicate discontinued status in the Scopus database