Epoxide-Based Synthetic Approaches toward Polypropionates and Related Bioactive Natural Products

Abstract

Polypropionate units are a common structural feature of many of the natural products in polyketides, some of which have shown a broad range of antimicrobial and therapeutic potential. Polypropionates are composed of a carbon skeleton with alternating methyl and hydroxy groups with a specific configuration. Different approaches have been developed for the synthesis of polypropionates and herein we include, for the first time, all of the epoxide-based methodologies that have been reported over the years by several research groups such as Kishi, Katsuki, Marashall, Miyashita, Prieto, Sarabia, Jung, McDonald, etc. Several syntheses of polypropionate fragments and natural products that employed epoxides as key intermediates have been described and summarized in this review. These synthetic approaches involve enatio- and diastereoselective synthesis of epoxides (epoxy-alcohols, epoxy-amides, and epoxy-esters) and their regioselective cleavage with carbon and/or hydride nucleophiles. In addition, we included a description of the isolation and biological activities of the polypropionates and related natural products that have been synthetized using epoxide-based approaches. In conclusion, the epoxide-based methodologies are a non-aldol alternative approach for the construction of polypropionate.

Exploring the synthetic potential of epoxide ring opening reactions toward the synthesis of alkaloids and terpenoids: a review

“…Similarly, Bugarin and allies, provided a review on the syntheses of polypropionates and other bioactive natural products by using epoxide chemistry in 2023. 51 Our review focuses on the formation of alkaloids and terpenoids due to the comprehensive work reported on the syntheses of these natural products by involving epoxide ring opening reaction as one of the key steps, reported within the past decade (2014–2023).…”

Extraction, Isolation, Characterization, and Bioactivity of Polypropionates and Related Polyketide Metabolites from the Caribbean Region

“…This reaction produces poly-β-keto chains (Figure 2) catalyzed by the multifunctional enzymes polyketide synthases (PKSs) [2]. In this review, we will focus on the discussion of the polypropionates group that can be classified into subgroups, including macrolides, and linear and cyclic polyethers (Figure 2) [3,4]. Type I PKS is responsible for polypropionate macrolide biosynthesis, where the Claisen condensation employs either acetyl-CoA or, normally, propionyl-CoA (C 3 -units), or both [1].…”

Azetidine synthesis by La(OTf)3-catalyzed intramolecular regioselective aminolysis of cis-3,4-epoxy amines

“…Arranging specific polar functional groups in three-dimensional space is a basic strategy for imparting a specific bioactive function to organic molecules and is universally found in nature and used in medicinal chemistry. The regioselective nucleophilic ring opening of epoxides is an efficient strategy for constructing contiguous chiral centers, and many methods have been developed to achieve this reaction ( Caron and Sharpless, 1985 ; Faiz and Zahoor, 2016 ; Wang, 2017 ; Rodríguez-Berríos et al, 2023 ). Aminolysis of epoxides is a useful reaction for the synthesis of sterically complex nitrogen-containing compounds such as alkaloids.…”