11-Step Total Synthesis of Araiosamines

A concise route to a small family of exotic marine alkaloids known as the araiosamines has been developed, and their absolute configuration has been assigned. The dense array of functionality, high polarity, and rich stereochemistry coupled with equilibrating topologies present an unusual challenge for chemical synthesis and an opportunity for innovation. Key steps involve the use of a new reagent for guanidine installation, a remarkably selective C–H functionalization, and a surprisingly simple final step that intersects a presumed biosynthetic intermediate. Synthetic araiosamines were shown to exhibit potency against Gram-positive and -negative bacteria despite a contrary report of no activity

Switching Off the Charge Transfer and Closing the S₁–T₁ ISC Channel in Excited States of Quinolizinium Derivatives: A Theoretical Study

Excited states of benzo­[<i>b</i>]­quinolizinium (<b>BQ</b>) derivatives that show efficient pH-responsive fluorescence switching properties were studied quantum-chemically by employing the CASSCF/CASPT2 and TD-DFT methods. Protonation of aminophenyl-<b>BQ</b> at the electron-donor amine moiety converts the nitrogen lone pair into a σ bond and the HOMO into a lower-lying orbital that is no longer involved in the excitation, thereby rationalizing the suppression of the charge transfer. An S₁–T₁ seam between the vertically excited Franck–Condon (FC) point and the S₁ equilibrium geometry favors intersystem crossing (ISC). The T₁ state of the protonated form remains well below S₁ (1.5 eV) because of favorable exchange interactions, whereas the T₁ state of the unprotonated form does not experience any analogous stabilization because of the difference in the spatial domains of the singly occupied orbitals in the S₁ and T₁ states. The S₁ surface from the FC point until the equilibrium geometry for the protonated species is energetically downhill. Calculations on models and available experimental data suggest design principles for similarly functioning pH-responsive species, namely, an amine lone pair as the electron donor and a cationic ring of moderate size as the electron acceptor that are structurally separated by virtue of a spacer

Stereochemical Determination of the Leupyrrins and Total Synthesis of Leupyrrin A₁

The stereochemical determination of the potent antifungal agents leupyrrin A₁ and B₁ and the total synthesis of leupyrrin A₁ are reported. The relative and absolute configuration was determined by a combination of high field NMR studies, molecular modeling, and chemical derivatization. The expedient total synthesis involves a one-pot sequential Zr-mediated oxidative diyne-cyclization/regioselective opening sequence for preparation of the unique dihydrofuran ring, a highly stereoselective one-pot approach to the butyrolactone, a challenging sp²–sp³ Suzuki coupling and a high-yielding Shiina macrolactonization