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., cis-pinonic acid) are typically used as surrogates to quantify both monomeric and dimeric SOA constituents. Here, we synthesize a series of enantiopure, pinene-derived carboxylic acid and dimer ester homologues. We find that the ()ESI efficiencies of the dimer esters are 19-36 times higher than that of cis-pinonic acid, demonstrating that the mass contribution of dimers to monoterpene SOA has been significantly overestimated in past studies. Using the measured ()ESI efficiencies of the carboxylic acids and dimer esters as more representative surrogates, we determine that molecular products measureable by LC/()ESI-MS account for only 21.8  2.6% and 18.9  3.2% of the mass of SOA formed from ozonolysis of -pinene and -pinene, respectively. The 28-36 identified monomers (C 7-10 H 10-18 O 3-6) constitute 15.6-20.5% of total SOA mass, whereas only 1.3-3.3% of the SOA mass is attributable to the 46-62 identified dimers (C 15-19 H 24-32 O 4-11). The distribution of identified pinene and -pinene SOA molecular products is examined as a function of carbon number (n C), average carbon oxidation state (C), and volatility (C*). The observed order-of-magnitude OS difference in ()ESI efficiency between monomers and dimers is expected to be broadly applicable to other biogenic and anthropogenic SOA systems analyzed via () or (+) LC/ESI-MS under various LC conditions, and demonstrates that the use of unrepresentative surrogates can lead to substantial systematic errors in quantitative LC/ESI-MS analyses of SOA.

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 to complete the total synthesis. File list (3) download file view on ChemRxiv ScabrolideAManuscriptFinalDraft.pdf (479.10 KiB) download file view on ChemRxiv TOCGraphic.pdf (129.56 KiB) download file view on ChemRxiv ScabrolideSIFinal.pdf (13.10 MiB)

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. In this work we show that the antioxidant properties of TBHQ are not responsible for the inhibition of HA-mediated entry. In addition, we have performed a structure-activity relationship (SAR) analysis of TBHQ derivatives. We find that the most promising compound, 3-tert-butyl-4-methoxyphenol, exhibits enhanced potency (IC = 0.6 μM), decreased toxicity (CC = 340 μM), and increased stability (t > 48 h). Finally, we have characterized the binding properties of 3-tert-butyl-4-methoxyphenol using NMR and molecular dynamics to guide future efforts for chemical optimization.

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. A challenging Zn-mediated Barbier allylation then forges the final C–C bond and also establishes two vicinal stereogenic centers. Finally, a Cu-catalyzed aerobic oxidation facilitates the formation of the β-hydroxybutanolide to complete the total synthesis.

In this study we revisit one of the simplest RO2 + RO2 reactions: the self-reaction of the ethene-derived hydroxyperoxy radical formed via sequential addition of OH and O2 to ethene....