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Indolditerpen eaflavi nine (panel 1 of Fig. 1, colorless needles, melting point 102oC) is a fascinating molecule with a remarkable history that can be traced back to 1980 when the Clardy and co-workers performed the first isolation from sclerotia of Aspergillusflavus and elucidated the structure of the compound (Fig 1, different Aflavinines). Its biological activities and numerous uses have been investigated extensively over the years, and the results of these studies are summarised in this article. Efforts to investigate the biological activity of Aflavinine and to find other Aflavinine congeners have continued following the isolation and determination of the Aflavinine structural formula in the laboratory. Following the discovery of the structure, many total synthesis procedures have been carried out, which are briefly discussed below.

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.

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