Chemoenzymatic Synthesis of the Antifungal Compound (–)‐Pestynol by a Convergent, Sonogashira Construction of the Central Yne‐Diene

Abstract

A total synthesis of the fungal‐derived natural product pestynol is reported via a convergent chemoenzymatic approach from the readily available precursors geranyl bromide, ethyl acetoacetate, trimethylsilylacetylene, and bromobenzene. Synthetic (–)‐pestynol proved to be identical in all respects to the natural material, allowing confirmation of the structure including absolute stereochemistry.

Regio‐ and Enantioselective Synthesis of Sulfone‐Bearing Quaternary Carbon Stereocenters by Pd‐Catalyzed Allylic Substitution

“…Recognizing the synthetic importance of these enantioenriched quaternary center‐containing sulfones, we applied this newly established method to a concise total synthesis of the antimicrobial and antifungal agent (+)‐Agelasidine A ( 6 ) . To achieve this goal, we focused on the reaction of vinyl cyclic carbonate ( 1 h ), synthesized from ( E )‐geranylacetone, and sodium 2‐acetoxyethane‐1‐sulfinate ( 2 w ). To our delight, we were happy to find that vinyl cyclic carbonate ( 1 h ) can be coupled with 2 w to provide the desired tertiary allylic sulfone 3 hw in 65 % isolated yield with high selectivity (92 % ee , >19:1 b/l) under our standard conditions (Table , Entry 1).…”

Bypassing Biocatalytic Substrate Limitations in Oxidative Dearomatization Reactions by Transient Substrate Mimicking

“…The product 3,5-diene-1,2-diol structural portion can be further modified at the diol (e.g., by Claisen rearrangements) and the diene (e.g., by oxidative cleavage and (cyclo-)­addition reactions), thus providing versatile precursors for natural product synthesis. Because of this synthetic value of dioxygenase products, these enzymes have since been exploited in many total syntheses. , Another important biosynthetic dearomative reaction is the oxidative dearomatization of phenols catalyzed by monooxygenases. Pioneering work by the Cox and Tang groups revealed this transformation as the key step in the biosyntheses of a variety of fungal natural products (Figure ): for example, aldehyde 1 gets oxidatively dearomatized by AzaH to give 2 , which upon cyclization delivers the azaphilone derivative azanigerone E ( 3 ) .…”

Regio‐ and Enantioselective Synthesis of Sulfone‐Bearing Quaternary Carbon Stereocenters by Pd‐Catalyzed Allylic Substitution

“…Notably,i n most cases,the branched allylic products were obtained with excellent regioselectivity (> 19:1). [8c] To achieve this goal, we focused on the reaction of vinyl cyclic carbonate (1h), synthesized from (E)-geranylacetone, [25] and sodium 2-acetoxyethane-1-sulfinate (2w). Theabsolute configuration of sulfone 3ua (R)was confirmed by X-ray analysis ( Table 3, inset at the right).…”