A Highly Convergent and Biomimetic Total Synthesis of Portentol

An efficient total synthesis of the unusual polyketide portentol is reported. Three boron aldol reactions were used to assemble the linear carbon chain of the natural product, which contains two challenging <i>anti</i>−<i>anti</i> stereotriads. A biomimetic double cyclization cascade, triggered by an oxidation, then afforded portentol and its known dehydration product, anhydroportentol. The biosynthesis of portentol and the biosynthetic relevance of our key step are discussed

Concise Synthesis of Glycerophospholipids

Glycerophospholipids are major components of cellular membranes and provide important signaling molecules. Besides shaping membrane properties, some bind to specific receptors to activate biological pathways. Untangling the roles of individual glycerophospholipids requires clearly defined molecular species, a challenge that can be best addressed through chemical synthesis. However, glycerophospholipid syntheses are often lengthy due to the contrasting polarities found within these lipids. We now report a general strategy to quickly access glycerophospholipids via opening of a phosphate triester epoxide with carboxylic acids catalyzed by Jacobsen’s Co(salen) complex. We show that this method can be applied to a variety of commercially available fatty acids, photoswitchable fatty acids, and other carboxylic acids to provide the corresponding glycerophosphate derivatives

Asymmetric Synthesis of the Antiviral Diterpene Wickerol A

Wickerol A (<b>1</b>) is an unusual diterpene with remarkable activity against the H1N1 influenza virus. Its tetracyclic skeleton contains three quaternary carbons and is marked by several <i>syn</i>-pentane interactions which force a six-membered ring into a twist-boat conformation. We present an asymmetric synthesis of wickerol A (<b>1</b>) that is based on a Jung Diels–Alder reaction, an intramolecular alkylation to complete the 6–5–6–6 ring system, and a conjugate addition, all of which overcome considerable steric strain. During the synthesis, we isolated an unexpected cyclopropane that presumably stems from a carbonium ion intermediate

Concise Synthesis of Glycerophospholipids

Glycerophospholipids are major components of cellular membranes and provide important signaling molecules. Besides shaping membrane properties, some bind to specific receptors to activate biological pathways. Untangling the roles of individual glycerophospholipids requires clearly defined molecular species, a challenge that can be best addressed through chemical synthesis. However, glycerophospholipid syntheses are often lengthy due to the contrasting polarities found within these lipids. We now report a general strategy to quickly access glycerophospholipids via opening of a phosphate triester epoxide with carboxylic acids catalyzed by Jacobsen’s Co(salen) complex. We show that this method can be applied to a variety of commercially available fatty acids, photoswitchable fatty acids, and other carboxylic acids to provide the corresponding glycerophosphate derivatives

Thiocarbonyl Ylide Chemistry Enables a Concise Synthesis of (±)-Hippolachnin A

Hippolachnin A (<b>1</b>) is an antifungal polyketide that bristles with ethyl groups mounted onto a caged heterotricyclic core. It has shown potent activity against Cryptococcus neoformans, a yeast that can affect immunocompromised patients as an opportunistic pathogen. Herein we describe a concise, diversifiable, and scalable synthesis of (±)-hippolachnin A (<b>1</b>). It features a powerful photochemical opening step, a diastereoselective addition of an ethyl cuprate and an unusual strategy to install two additional ethyl groups that makes use of a thiocarbonyl ylide generated <i>in situ</i>

Selective Synthesis of Divergolide I

Divergolide I (<b>1</b>) is a naphthoquinone ansamycin that exhibits broad antibacterial activity. Its tetracyclic ring system is believed to be biosynthetically assembled via ring contraction of a macrocyclic precursor (<i>proto</i>-divergolide) that is both a macrolactone and a macrolactam. We here report a convergent and enantioselective synthesis that delivers the target molecule in less than 20 linear steps. Our work establishes the absolute configuration of divergolide I, confirms its relative configuration, and demonstrates that the biomimetic cyclization of a <i>proto</i>-divergolide can be surprisingly selective

Furans as Versatile Synthons: Total Syntheses of Caribenol A and Caribenol B

Two complex norditerpenoids, caribenols A and B, were accessed from a common building block. Our synthesis of caribenol A features the diastereoselective formation of the seven-membered ring through a Friedel–Crafts triflation and a late-stage oxidation of a furan ring. The first synthesis of caribenol B was achieved using an intramolecular organocatalytic α-arylation. An unusual intramolecular aldol addition was developed for the assembly of its cyclopentenone moiety, and the challenging <i>trans</i>-diol moiety was installed through a selective nucleophilic addition to a hydroxy 1,2-diketone. Our overall synthetic strategy, which also resulted in a second-generation synthesis of amphilectolide, confirms the usefulness of furans as powerful nucleophiles and versatile synthons

Azomethine Ylide Cycloaddition Approach toward Dendrobine: Synthesis of 5‑Deoxymubironine C

A concise route to the azatricyclo­[6.2.1.0^4,11]­undecane core of (−)-dendrobine and (−)-mubironine C is described wherein an unstabilized azomethine ylide cycloaddition provides the complete carbon framework of the natural products. The cyclization precursor is made in short order from (<i>R</i>)-carvone through an unconventional high-pressure Ireland–Claisen reaction. Attempts to install a final hydroxyl group through an intramolecular lactonization strategy and the observation of an unexpected and highly complex enal–ene product are also reported

Total Synthesis of Lycopladine A and Carinatine A via a Base-Mediated Carbocyclization

A concise, enantioselective synthesis of lycopladine A and carinatine A is presented. Our synthetic approach hinges on the recently developed mild carbocyclization of ynones to furnish the hydrindane core of the alkaloids. Their pyridine ring was efficiently installed using the Ciufolini method. Both heterocycles of carinatine A, a rare naturally occurring nitrone, were formed in a single operation

Intramolecular Vinyl Quinone Diels–Alder Reactions: Asymmetric Entry to the Cordiachrome Core and Synthesis of (−)-Isoglaziovianol

A short and asymmetric entry to the core structure of the cordiachromes has been developed, allowing access to (−)-isoglaziovianol in seven steps. Our synthesis includes a Trost asymmetric allylic alkylation and a reaction cascade triggered by a vinyl quinone Diels–Alder reaction and followed by intramolecular nucleophilic interception