Cuban and Brazilian red bee propolis (CRP and BRP), a waxy red substance made by bees and found on the outside of beehives, has been used for thousands of years in folk medicine to treat a wide range of ailments. Hundreds of compounds have been isolated from CRP and BRP, however, very little is known about the individual components and their contributions to the biological activity of the propolis as a whole. Of the compounds isolated, many are simple isoflavans, complex isoflavanoids, or dimeric isoflavanoids. Herein, we report the total syntheses of isoflavanoid natural products isolated from Cuban and Brazilian red bee propolis: neovestitol, retusapurpurin A, and retusapurpurin B, as well efforts towards the total synthesis of the dimeric isoflavanoid propolone B. The synthetic strategies described will allow for biological testing on these natural products, as well unnatural analogs.
Neovestitol, a simple isoflavan, has displayed interesting anti-inflammatory activity in mice. However, to the best of our knowledge, no syntheses of the natural product have been reported. Herein, we report the development of a [4 + 2] cycloaddition to access the neovestitol core. Furthermore, we developed a dynamic acylative kinetic resolution that led to the synthesis of enantiopure (S)-neovestitol. The asymmetric synthesis allowed for confirmation of the absolute stereochemistry of the isolated natural product, which had previously only been assigned based on analogy with related isoflavans.
Retusapurpurins A and B are complex isoflavanoids that are often attributed with giving red bee propolis a red color. Additionally, these compounds contain a neovestitol subunit. In this thesis, we describe the development of a novel annulation promoted by bis(trifluoromethane)sulfonimide that enabled us to construct the retusapurpurin core. This methodology was used to synthesize a small library of unnatural retusapurpurin analogs.
More recently, a new class of dimeric isoflavanoids were reported, propolones A-D, propolonones A-C, and propolol A. Of the eight compounds, propolones A-C and propolonones A and B contain a neovestitol subunit. Herein, we describe our efforts towards using a platinum(II)-catalyzed migratory cycloisomerization that would allow for access to these eight natural products, as well as unnatural analogs. / 2025-09-18T00:00:00Z
| Identifer | oai:union.ndltd.org:bu.edu/oai:open.bu.edu:2144/46936 |
| Date | 18 September 2023 |
| Creators | Marrs, Mackenzie |
| Contributors | Porco, Jr., John A. |
| Source Sets | Boston University |
| Language | en_US |
| Detected Language | English |
| Type | Thesis/Dissertation |
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