Systematic Route to Construct the 5-5-6 Tricyclic Core of Furanobutenolide-Derived Cembranoids and Norcembranoids.

Herein, we present a highly efficient method for constructing the intricate 5-5-6 fused ring system commonly found in the polycyclic furanobutenolide-derived cembranoid and norcembranoid natural product family with remarkable diastereoselectivity, utilizing an intramolecular Diels-Alder reaction as the cornerstone. Notably, employing a propargyl ether tether as the dienophile yields significant enhancements in the transformation process compared to its propargyl ester counterpart, as demonstrated in our previous total synthesis of havellockate. This advancement holds promising implications for future investigations, offering a streamlined pathway for rapidly assembling the tricyclic core characteristic of this diverse family of natural products.

Particle-phase accretion forms dimer esters in pinene secondary organic aerosol.

Secondary organic aerosol (SOA) is ubiquitous in the atmosphere and plays a pivotal role in climate, air quality, and health. The production of low-volatility dimeric compounds through accretion reactions is a key aspect of SOA formation. However, despite extensive study, the structures and thus the formation mechanisms of dimers in SOA remain largely uncharacterized.

Total synthesis of (-)-scabrolide A and (-)-yonarolide.

The complete account of the total syntheses of scabrolide A and yonarolide is disclosed. This article describes an initial approach involving a bio-inspired macrocyclization/transannular Diels-Alder cascade, which ultimately failed due to undesired reactivity during macrocycle construction. Next, the evolution of a second and third strategy, which both involve an initial intramolecular Diels-Alder reaction followed by a late-stage closure of the seven-membered ring of scabrolide A are detailed.

Asymmetric Total Synthesis of Havellockate.

The first total synthesis of the furanobutenolide-derived cembranoid diterpenoid havellockate is disclosed. Our convergent strategy employs a Julia-Kocienski olefination to join two enantioenriched fragments to produce a diene that is subsequently used in a propiolic acid esterification/Diels-Alder cascade. This sequence generates the fused carbocyclic core of the natural product in short order.

Investigations of an Unexpected [2+2] Photocycloaddition in the Synthesis of (-)-Scabrolide A from Quantum Mechanics Calculations.

We utilize ab initio quantum mechanics calculations to evaluate a range of plausible mechanistic pathways for the unexpected formation of a [6-4-4] ring system from an enone-olefin photocycloaddition in the synthesis of (-)-scabrolide A, previously reported by our group. We present a mechanistic analysis that is consistent with all current experimental observations, including the photoexcitation, the C-C bond formation, and the associated chemo- and diastereoselectivity.

Catalytic enantioselective synthesis of carbocyclic and heterocyclic spiranes a decarboxylative aldol cyclization.

The synthesis of a variety of enantioenriched 1,3-diketospiranes from the corresponding racemic allyl β-ketoesters an interrupted asymmetric allylic alkylation is disclosed. Substrates possessing pendant aldehydes undergo decarboxylative enolate formation in the presence of a chiral Pd catalyst and subsequently participate in an enantio- and diastereoselective, intramolecular aldol reaction to furnish spirocyclic β-hydroxy ketones which may be oxidized to the corresponding enantioenriched diketospiranes. Additionally, this chemistry has been extended to α-allylcarboxy lactam substrates leading to a formal synthesis of the natural product (-)-isonitramine.

Synthesis of Carboxylic Acid and Dimer Ester Surrogates to Constrain the Abundance and Distribution of Molecular Products in α-Pinene and β-Pinene Secondary Organic Aerosol.

Liquid chromatography/negative electrospray ionization mass spectrometry [LC/(-)ESI-MS] is routinely employed to characterize the identity and abundance of molecular products in secondary organic aerosol (SOA) derived from monoterpene oxidation. Due to a lack of authentic standards, however, commercial terpenoic acids (e.g.

The Total Synthesis of (-)-Scabrolide A.

The first total synthesis of the norcembranoid diterpenoid scabrolide A is disclosed. The route begins with the synthesis of two chiral pool-derived fragments, which undergo a convergent coupling to expediently introduce all 19 carbon atoms of the natural product. An intramolecular Diels-Alder reaction and an enone-olefin cycloaddition/fragmentation sequence are then employed to construct the fused [5-6-7] linear carbocyclic core of the molecule and complete the total synthesis.

Stabilization and Improvement of a Promising Influenza Antiviral: Making a PAIN PAINless.

The viral envelope protein hemagglutinin (HA) plays a critical role in influenza entry and thus is an attractive target for novel therapeutics. The small molecule tert-butylhydroquinone (TBHQ) has previously been shown to bind to HA and inhibit HA-mediated entry with low micromolar potency. However, enthusiasm for the use of TBHQ has diminished due to the compound's antioxidant properties.