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This review seeks to offer an overview of the history, biology, chemistry, and complete synthesis of Aflavinines, as well as information on specific aspects of each. The discovery and structural elucidation of this molecule by Clardy and colleagues in 1980 may be traced back to its discovery and characterization. The majority of previously published complete syntheses were addressed in a concise overview, with the most important features of each study being underlined. Furthermore, a number of Aflavinines congeners with antiinsectant and antiviral properties are discussed. To the best of our knowledge, this evaluation is nearly the first in the field of Aflavinine themes, and it covers all elements in brief.

Its isolation, structural elucidation, biological activity, synthetic technique, and a brief summary of its chemistry are all discussed in this section. In spite of the fact that its primary biological activity has been found as an insecticide [2-7], this section discusses various biological activities focused on antiviral and anticancer drugs. We hope that the current critical review will energise researchers to capture the most up-to-date information about Aflavinines history, chemistry, biology, and recent achievements in order to investigate further potential activities of this interesting and synthetically challenging molecule for possible applications in further drug discovery purposes in the near future.

Fig 1. Some Selected Aflavinine Family Members

1. EXPERIMENTAL FACTOR

The study is analyzed on the basis of diverse factors related to the study and its area and also on the reviews of the diverse scholars on the Aflavinine. These are:

1.1 Chemsitry Historical Aspect

The Aflavinine family consists of six or seven stereogeniccentres with two vicinal quaternary carbons, with the exception of the anominine (panel 6 of Fig. 1). The anominine is the only member of the family that differs from the others in this regard. Fig. 2 depicts the overall numbering of Aflavinine in a graphical format. Various Aflavinine congeners have been discovered and reported over the course of history. Because of the tightly fused ring structure with 6 to 7 stereogenic centers, it becomes a significant problem for synthetic chemists to place the hydroxyl group in the C(15) and C(20) neighboring locations to the vicinal quaternary centers on a majority of the occasions. This complicated structure possesses anticancer and antiviral properties; however its antiinsectant activity is primarily restricted to insects.

Because of the limited availability of Aflavinine in natural goods, synthetic obstacles have developed in order to provide it conveniently through commercial manufacture up to this point in time. When it comes to mycotoxin and other closely related fungal metabolites, Stefan and co-workers explore the chemistry and biology of these compounds in their review study. Rank and colleagues investigated the differences and similarities in the chemistry of Aspergillusflavus and Aspergillusoryzae. Soudo and colleagues revealed the findings of their research on the sclerotic of various species of the Aspergillus genus. The literature also contains discussions on numerous other secondary metabolites produced by Aspergillusflavus.

Fig 2 Aflavinines Numbering

1.2  The First Total Synthesis by Danishefsky and coworkers in 1985

Danishefsky and colleagues published the first complete synthesis of 3-desmethyl Aflavinine, an Aflavinine analogue, in 1985, marking the first time that this had been done (Fig. 3.) [22]. The one-pot procedure of forming a sterically congested tricyclic framework by (2 + 2 + 2) annulation is the most notable feature of its synthesis to date. Unfortunately, this strategy of synthesising natural Aflavinine (panel 1 of Fig. 1) was not successful due to undesirable stereochemical results at the C(4) position.

Fig 3 Synthesis of 3-Desmethylafflavinine

Total Synthesis of Anominine and its Congener Tubingensin A by Li and Co-workers in 2012

It was announced by Li and colleagues in 2012 that the whole synthesis of anominine (panel 6 of fig 1) and its congener tubingensin A (panel 9 of fig 4), which is the parent molecule of the Aflavinine family, had been completed. They are able to synthesis the anominine and tubingensin from a common intermediate (fig. 4) that contains all of the required stereogeniccentres in this manner. For this purpose, they used the Sc(OTf)₃-mediated Mukalyamaaldol reaction in conjunction with the Ueno-Stork radical cyclization procedure to generate the stereocontrolled C-C bonds as a first step in assembling the crucial intermediate. A CuOTf-promoted -electrocyclization is used to generate the core of the pentacyclic scaffold in the case of tubingensin A, whereas a radical deoxygenation followed by side-chain installation is used in the case of anominine synthesis.

Fig 4 Overall Syntheses of Anominie (6) and Tubingensin A (9)

1.3 Kwak and Others A Method to Get to the Core of the Alfavinine Framework

A tandem intra-molecular Diels-Alder cyclo-addi on involving an alkynone linked to two 1,3-butadienes under Lewis acid-promoted reaction conditions has been described by Goldberg and colleagues. They employed the intra-molecular Diels-Alder cycloaddi on notion between two separate electron-rich furan rings coupled to an electron-deficient alkyne dienophile to get to the heart of Aflavinine synthesis, and they were successful (Fig. 5). We were able to accomplish stereocontrol by shielding the free alcohol with a large TIPS (triisopropylaminosilyl) group, which stimulated the formation of allylic1,3-strain and favoured the critical cycloaddition step. Because of the presence of a functional group and other substitution sites in this Aflavinine core, the structural chemistry of this Aflavinine core demonstrates an effective method for the synthesis of numerous synthetic analogues.

Fig 5 Tandem intramolecular Diels-Alder cycloddition synthesizes aflavinine

structural cores

Aflavinine to find the most up-to-date information from the time of its first appearance in literature in 1975 to the date of its last appearance in literature in 2020 March 02, among other search engines. Following the discovery of Aflavinine in 1980 Gloer and colleagues from Aspergillus discovered a number of structurally diverse congeners, including 10,11-dihydro-11,12-dehydro-20-hydroxy Aflavinine, 24,25-dehydro-10,11-dihydro-20-hydroxy Aflavinine, aflavazole, and anominine (panels 3-6 of Fig. 1). On the other hand, Nakadate and colleagues discovered 17-hydroxyeujindole (panel 7 of Fig. 1), as well as its dehydrated congener, which has a distinct ring fusion pattern.

Overall synthesis has been achieved, and continuing total synthesis together with reported biological activity and more testing has piqued researchers interests, as can be seen from this synopsis of the research. Aflavinines 46-year history reveals a gap between the first total synthesis approach and the second total synthesis, but its biological importance is rising as it is isolated from natural sources and its many congeners and analogues are isolated. Aflavinine's structural complexity is a major factor in why its synthesis has been delayed and commercial supply is still lacking. But the tale behind the entire synthesis of Aflavinine may also be an appreciative reflection of the art and craft of organic synthesis. That's what we'd want to see happen to Aflavinine, which is a very intriguing compound, after reading this brief assessment.

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