Remote oxidation of steroids by photolysis of attached benzophenone groups

The application of small molecules as catalysts for the diversification of natural product scaffolds is reviewed. Specifically, principles that relate to the selectivity challenges intrinsic to complex molecular scaffolds are summarized. The synthesis of analogs of natural products by this approach is then described as a quintessential “late-stage functionalization” exercise wherein natural products serve as the lead scaffolds. Given the historical application of enzymatic catalysts to the site-selective alteration of complex molecules, the focus of this review is on the recent studies of non-enzymatic catalysts. Reactions involving hydroxyl group derivatization with a variety of electrophilic reagents are discussed. C–H bond functionalizations that lead to oxidations, aminations, and halogenations are also presented. Several examples of site-selective olefin functionalizations and C–C bond formations are also included. Numerous classes of natural products have been subjected to these studies of site-selective alteration including polyketides, glycopeptides, terpenoids, macrolides, alkaloids, carbohydrates and others. What emerges is a platform for chemical remodeling of naturally occurring scaffolds that targets virtually all known chemical functionalities and microenvironments. However, challenges for the design of very broad classes of catalysts, with even broader selectivity demands (e.g., stereoselectivity, functional group selectivity, and site-selectivity) persist. Yet, a significant spectrum of powerful, catalytic alterations of complex natural products now exists such that expansion of scope seems inevitable. Several instances of biological activity assays of remodeled natural product derivatives are also presented. These reports may foreshadow further interdisciplinary impacts for catalytic remodeling of natural products, including contributions to SAR development, mode of action studies, and eventually medicinal chemistry.

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“…A shorter tether length forces oxidation at C15, while a longer tether allows the benzophenone oxidant to reach C17–H. 192–194 …”

Section: Figurementioning

confidence: 99%

Applications of Nonenzymatic Catalysts to the Alteration of Natural Products

2017

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“…The aglycone of pavoninin-4 (24) can be also be synthesized from diosgenin 7 via (25R)-26-hydroxycholesterol (15) [33], using Breslow's remote functionalization [34] strategy, as shown in Scheme 2.…”

Section: Scheme 1 Synthesis Of the C15a Hydroxylated Steroid 14mentioning

confidence: 99%

Biological Activities and Syntheses of Steroidal Saponins: the Shark‐Repelling Pavoninins

Williams¹,

Gong²

2006

Lipids

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Steroidal saponins are complex compounds that have a steroid attached to a carbohydrate moiety. They are natural surfactants and detergents and exhibit a number of biological effects. Steroidal saponins have shown membrane-permeabilizing, hypocholesterolemic, immunostimulant, and anticancer properties. They have also been found to affect the growth, food intake and reproductive capabilities of animals. Furthermore, they have been shown to act as antiviral and antifungal agents. They have been isolated from many plants and some animals, especially sea cucumbers and starfish. Fish belonging to the species Pardachirus pavoninus excrete a mixture of six steroidal N-acetylglucosaminides, pavoninins 1-6, with shark-repelling properties. We report syntheses of the C-15alpha pavoninin-4 by both direct synthesis from diosgenin and by remote functionalization. A general solution for the glycosylation of hindered alcohols was developed using glycosyl fluorides as good glycosyl donors. The syntheses of two C-16beta structural analogs of OSW-1 are described.

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“…This inspired us to develop processes we called remote oxidation, in which we attached reagents and templates to substrates that could reach far from their attachment point (from ring A of the steroid all the way to ring D at the other end) and perform selective reactions on particular spots because of the geometry imposed by our attached reagent or template (12,13). In more recent work, we have learned how to imitate the enzyme more fully, achieving geometrically controlled turnover catalysis (14 -16).…”

mentioning

confidence: 99%