A Stereoselective Synthesis of (−)-Viridiofungin A Utilizing a TiCl₄-Promoted Asymmetric Multicomponent Reaction

A stereoselective synthesis of (−)-viridiofungin A is described. The convergent synthesis utilized a unique highly diastereoselective multicomponent reaction between optically active phenyldihydrofuran and an α-ketoester to provide two chiral centers including a quarternary carbon center in a single step. Other key steps include an acyloxycarbonium ion-mediated tetrahydrofuran ring-opening reaction and a Julia–Kocienski olefination

Enantioselective Syntheses of FR901464 and Spliceostatin A: Potent Inhibitors of Spliceosome

Enantioselective syntheses of FR901464 and spliceostatin A, potent spliceosome inhibitors, are described. The synthesis of FR901464 has been accomplished in a convergent manner in 10 linear steps (20 total steps). The <i>A</i>-tetrahydropyran ring was constructed from (<i>R</i>)-isopropylidene glyceraldehyde. The functionalized tetrahydropyran <i>B</i>-ring was synthesized utilizing a Corey–Bakshi–Shibata reduction, an Achmatowicz reaction, and a stereoselective Michael addition as the key steps. Coupling of <i>A</i>- and <i>B</i>-ring fragments was accomplished via cross-metathesis

Correction to Enantioselective Total Synthesis of (+)-Amphirionin‑4

Correction to Enantioselective Total Synthesis of (+)-Amphirionin‑

Enantioselective Synthesis of Both Epimers at C‑21 in the Proposed Structure of Cytotoxic Macrolide Callyspongiolide

Both epimers at C-21 in the proposed structure of (+)-callyspongiolide have been synthesized in a convergent and enantioselective manner. The 14-membered macrolide with a sensitive C2–C3 <i>cis</i>-olefin functionality was installed by a Yamaguchi macrolactonization of hydroxyl alkynoic acid followed by hydrogenation over Lindlar’s catalyst. The C5 methyl stereocenter was constructed by a ring-closing olefin metathesis followed by addition of methyl cuprate to an α,β-unsaturated δ-lactone. Other key reactions are chiral Corey–Bakshi–Shibata (CBS) reduction and Sonogashira coupling to conjoin the macrocyclic core and side chain

Stereoselective Synthesis of Both Tetrahydropyran Rings of the Antitumor Macrolide, (−)-Lasonolide A

Stereoselective syntheses of both functionalized tetrahydropyran subunits of (−)-lasonolide A are described. These tetrahydropyran rings were constructed using catalytic asymmetric hetero Diels–Alder reactions as the key steps. The C22 quaternary stereocenter present in the upper tetrahydropyran ring was constructed by a stereoselective alkylation, and the C9 hydroxy stereochemistry of the bottom tetrahydropyran was constructed by a stereoselective epoxidation followed by a regioselective epoxide opening reaction

Enantioselective Total Synthesis of Pladienolide B: A Potent Spliceosome Inhibitor

An enantioselective and convergent total synthesis of pladienolide B (<b>1</b>) is described. Pladienolide B binds to the SF3b complex of a spliceosome and inhibits mRNA splicing activity. The synthesis features an epoxide opening reaction, an asymmetric reduction of a β-keto ester, and a cross metathesis strategy for the side chain synthesis

Enantioselective Total Synthesis of (+)-Lithospermic Acid

An enantioselective synthesis of (+)-lithospermic acid, a potent anti-HIV agent, has been accomplished in a convergent manner in nine steps. The synthesis features an enantioselective intramolecular oxa-Michael addition catalyzed by a quinidine derivative, a hypervalent iodine-mediated rearrangement of chromanone to dihydrobenzofuran, an enantioselective α-oxyamination, and an intermolecular C–H olefination

TiCl₄-Promoted Tandem Carbonyl or Imine Addition and Friedel–Crafts Cyclization: Synthesis of Benzo-Fused Oxabicyclooctanes and Nonanes

A new and convenient synthesis of benzo-fused 8-oxabicyclo[3.2.1]octane and 9-oxabicyclo[4.2.1]nonane derivatives are described. The reaction involved a TiCl₄-mediated tandem carbonyl or imine addition followed by a Friedel–Crafts cyclization to provide these functionalized derivatives in good to excellent yields and high diastereoselectivity

TiCl₄-Promoted Tandem Carbonyl or Imine Addition and Friedel–Crafts Cyclization: Synthesis of Benzo-Fused Oxabicyclooctanes and Nonanes

A new and convenient synthesis of benzo-fused 8-oxabicyclo[3.2.1]octane and 9-oxabicyclo[4.2.1]nonane derivatives are described. The reaction involved a TiCl₄-mediated tandem carbonyl or imine addition followed by a Friedel–Crafts cyclization to provide these functionalized derivatives in good to excellent yields and high diastereoselectivity

Total Synthesis of GEX1Q1, Assignment of C‑5 Stereoconfiguration and Evaluation of Spliceosome Inhibitory Activity

An enantioselective total synthesis of GEX1Q1 has been accomplished in a convergent manner. The C-5 asymmetric center has now been assigned through synthesis. GEX1Q1 displayed slightly better spliceosome inhibitory activity over its C-5 epimer. The salient features of this synthesis include an asymmetric hetero-Diels–Alder reaction to construct the tetrahydropyran ring and a Suzuki cross-coupling to assemble the key segments