Current Organic Chemistry - Volume 25, Issue 4, 2021

Indoxamycins A-F, a novel class of polyketides, were isolated from the saline culture of marine-derived actinomyces by Sato et al. in 2009. Intriguing stereochemical complexity involving tricyclic [5.5.6] cage-like structures with six consecutive chiral centers challenged many organic chemists. Chemical ingenuity, implementation of pioneered reactions along with fine chemical transformations allowed not only the rapid construction of the central core but also allowed minor structural revision and paved the information to delineate the absolute stereostructures of these complex polyketide marine natural products. To achieve the central core structure in indoxamycins A-F, reactions like the Ireland-Claisen rearrangement, an enantioselective 1,6-enyne reductive cyclization, and one-pot cascade reactions of 1,2- addition/oxa-Michael/methylenation were employed. Using the chiral pool approach, the readily available R-carvone was employed as a cost-effective starting material to achieve the concise total syntheses of (-)-indoxamycins A and B, in which Pauson-Khand, Cu-catalyzed Michael addition and tandem retro-oxa-Michael addition/1,2-addition/oxa-Michael addition reactions were employed. The antipodes, (+)-indoxamycins can be easily accessed by simply switching to S-carvone as the starting material. Synthetically prepared indoxamycins A-F are devoid of antiproliferative properties, which disagree with the work reported by Sato and co-workers for (-)- indoxamycins A and F. Nevertheless, ready access to such complex natural products allows probing the untapped potential biological activities of these polyketides including cytotoxicity. A concise overview of interesting, key chemical transformations including named reactions in establishing the architecture of indoxamycins was compiled to inspire organic chemists and help reinvigorate novel strategies for the asymmetric synthesis as well as the development of novel derivatives of indoxamycins with unique physicochemical and biological properties.

Seven membered heterocyclic Azepine and its derivatives have great pharmacological and therapeutic implications. In this review, the literature of the last fifty years has been exploited for the synthesis, reaction, and biological properties of these seven-member heterocyclic compounds. Most of the mechanisms involved the ring expansion of either five or six-membered compounds using various methods such as thermally, photo-chemically, and microwave irradiation. The systematically designed schemes involve the synthesis of different derivatives of azepine, azepinone, azepane, etc., using similar moieties by various researchers. However, there is much work yet to be done in the biological section, as it is not explored and reported in the literature; therefore, N-containing seven-membered heterocycles still have much scope for the researchers.

The ocean supplies abundant active compounds, including small organic molecules, proteins, lipids, and carbohydrates, with diverse biological functions. The high-value transformation of marine carbohydrates primarily refers to their pharmaceutical, food, and cosmetic applications. However, it is still a big challenge to obtain these marine carbohydrates in well-defined structures. Synthesis is a powerful approach to access marine oligosaccharides, polysaccharide derivatives, and glycomimetics. In this review, we focus on the chemical synthesis of marine acidic carbohydrates with uronic acid building blocks such as alginate, and glycosaminoglycans. Regioselective sulfation using a chemical approach is also highlighted in the synthesis of marine oligosaccharides, as well as the multivalent glycodendrimers and glycopolymers for achieving specific functions. This review summarizes recent advances in the synthesis of marine acidic carbohydrates, as well as their preliminary structure activity relationship (SAR) studies, which establishes a foundation for the development of novel marine carbohydrate-based drugs and functional reagents.

C-1 substituted tetrahydroisoquinolines have emerged as important scaffolds in pharmaceutical and medical research. Although various methods for α-substitution on tetrahydroisoquinolines have been discovered, the introduction of the azole group at C-1 position remains a challenge. Recently, direct C-H activation methods and multicomponent reactions have been employed towards the synthesis of azole containing tetrahydroisoquinolines. A summary of such synthetic strategies is presented here as these promising methods can help in developing more efficient synthetic routes. This minireview covers the available synthetic methods and their mechanistic pathways for the preparation of C-1 azole substituted tetrahydroisoquinolines.

The regioselectivity of the reaction of 2,5-dihydroxy-[1,4]-benzoquinone (DHBQ) with diamines could not be explained satisfactorily so far. In general, the reaction products can be derived from the tautomeric ortho-quinoid structure of a hypothetical 4,5-dihydroxy- [1,2]-benzoquinone. However, both aromatic and aliphatic 1,2-diamines form phenazines, in some cases, formally by diimine formation on the quinoid carbonyl groups, and in other cases, the corresponding 1,2-diamino-[1,2]-benzoquinones by nucleophilic substitution of the OH groups; the regioselectivity apparently does not follow any discernible pattern. The reactivity was now explained by an adapted theory of strain-induced bond localization (SIBL). Here, the preservation of the "natural" geometry of the two quinoid C–C double bonds (C3=C4 and C5=C6) as well as the N–N distance of the co-reacting diamine are crucial. A decrease of the annulation angle sum (N–C4–C5 + C4–C5–N) is tolerated well and the 4,5-diamino-ortho-quinones, having relatively short N–N spacings, are formed. An increase in the angular sum is energetically unfavorable, so that diamines with a larger N–N distance afford the corresponding ortho-quinone imines. Thus, for the reaction of DHBQ with diamines, exact predictions of the regioselectivity and the resulting product structure can be made on the basis of simple computations of bond spacings and product geometries.