An official website of the United States government
Abstract Tetradecaphenyl‐p‐terphenyl (2) was synthesized from 2,3,5,6‐tetraphenyl‐1,4‐diiodobenzene (11) by two methods. Ullmann coupling of11with pentaphenyliodobenzene (9) gave compound2in 1.7 % yield, and Sonogashira coupling of11with phenylacetylene, followed by a double Diels‐Alder reaction of the product diyne12with tetracyclone (6), gave2in 1.5 % overall yield. The latter reaction also gave the monoaddition product 4‐(phenylethynyl)‐2,2′,3,3′,4′,5,5′,6,6′‐nonaphenylbiphenyl (13) in 4 % overall yield. The X‐ray structures of compounds2and13show them to possess core aromatic rings distorted into shallow boat conformations. Density functional calculations indicate that these unusual structures are not the lowest energy conformations in the gas phase and may be the result of packing forces in the crystal. In addition, while uncorrected DFT calculations indicate that the strain energy in compound2is approximately 50 kcal/mol, dispersion‐corrected DFT calculations suggest that it is essentially unstrained, due to compensating, favorable, intramolecular interactions of its many phenyl rings. An attempted synthesis of tetradecaphenyl‐o‐terphenyl (4) by reaction of diphenylhexatriyne (14) with three equivalents of tetracyclone at 350 °C gave only the diadduct 2‐(phenylethynyl)‐2′,3,3′,4,4′,5,5′,6,6′‐nonaphenylbiphenyl (15) in 17 % yield. Even higher temperatures failed to produce4and lowered the yield of15, perhaps due to rapid decomposition of the starting materials. Ullmann coupling of 3,4,5,6‐tetraphenyl‐1,2‐diiodobenzene (16) and compound9also failed to give compound4.
more »
« less
An oxidative photocyclization approach to the synthesis of Securiflustra securifrons alkaloids
Securines and securamines are cytotoxic alkaloids that contain reactive alkene and heterocyclic residues embedded in skeletons comprising four to six oxidized rings. This structural complexity imparts a rich chemistry to the isolates but has impeded synthetic access to the structures in the nearly three decades since their isolation. We present a flexible route to eight isolates that exemplify the three skeletal classes of metabolites. The route proceeds by the modular assembly of the advanced azides38and49(13 steps, 6 to 10% yield), sequential oxidative photocyclizations, and late-stage functional group manipulations. With this approach, the targets were obtained in 17 to 19 steps, 12 to 13 purifications, and 0.5 to 3.5% overall yield. The structure of an advanced intermediate was elucidated by microcrystal electron diffraction (MicroED) analysis. The route will support structure-function and target identification studies of the securamines.
more »
« less
- Award ID(s):
- 1954319
- PAR ID:
- 10498062
- Publisher / Repository:
- American Association for the Advancement of Science
- Date Published:
- Journal Name:
- Science
- Volume:
- 383
- Issue:
- 6685
- ISSN:
- 0036-8075
- Page Range / eLocation ID:
- 849 to 854
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Abstract This computational study explores the copper (I) chloride catalyzed synthesis of (E)‐1‐(2,2‐dichloro‐1‐phenylvinyl)‐2‐phenyldiazene (2Cl‐VD) from readily available hydrazone derivative and carbon tetrachloride (CCl4).2Cl‐VDhas been extensively utilized to synthesize variety of heterocyclic organic compounds in mild conditions. The present computational investigations primarily focus on understanding the role of copper (I) andN1,N1,N2,N2‐tetramethylethane‐1,2‐diamine (TMEDA) in this reaction, TMEDA often being considered a proton scavenger by experimentalists. Considering TMEDA as a ligand significantly alters the energy barrier. In fact, it is only 8.3 kcal/mol higher compared to the ligand‐free (LF) route for the removal of a chlorine atom to form the radical·CCl3but the following steps are almost barrierless. This intermediate then participates in attacking the electrophilic carbon in the hydrazone. Crucially, the study reveals that the overall potential energy surface is thermodynamically favorable, and the theoretical turnover frequency (TOF) value is higher in the case of Cu(I)‐TMEDA complex catalyzed pathway.more » « less
-
Abstract We report a facile synthesis of diindeno‐fused dibenzo[a,h]anthracene derivatives (DIDBA‐2Cl,DIDBA‐2Ph, andDIDBA‐2H)with different degrees of non‐planarity using three substituents (chloro, phenyl, and hydrogen) of various sizes. The planarization of their cores, as evidenced by the decreased end‐to‐end torsional angles, was confirmed by X‐ray crystallography. Their enhanced energy gaps with twisting were investigated by a combination of spectroscopic and electrochemical methods with density functional theory, which showed a transition from singlet open‐shell to closed‐shell configuration. Moreover, their doubly reduced states,DIDBA‐2Ph2−andDIDBA‐2H2−, were achieved by chemical reduction. The structures of dianions were identified by X‐ray crystallographic analysis, which elucidated that the electron charging further distorted the backbones. The electronic structure of the dianions was demonstrated by experimental and theoretical approaches, suggesting decreased energy gaps with larger non‐planarity, different from the neutral species.more » « less
-
Abstract Photolyses oftrans‐Fe(CO)3(P((CH2)n)3P) (n=10 (a), 12 (b), 14 (c), 16 (d), 18 (e)) in the presence of PMe3provide the first economical and scalable route to macrobicyclic dibridgehead diphosphines P((CH2)n)3P (1). These are isolated as mixtures ofin,in/out,outisomers that equilibrate with degeneratein,out/out,inisomers at 150 °C via pyramidal inversion at phosphorus. For the entire series, VT31P NMR data establish or boundKeq, rates, and activation parameters for a variety of phenomena, many of which involve homeomorphic isomerizations, topological processes by which certain molecules can turn themselves inside out (e. g.,in,in⇌out,out). This provides the first detailed mapping of such trends in homologous series of aliphatic bicyclic compounds XE((CH2)n)3EX with any type of bridgehead. Isomeric diborane adducts1 a,d ⋅ 2BH3are also characterized. Crystal structures ofout,out‐1 aandin,in‐1 a ⋅ 2BH3aid isomer assignments and reveal unusual cage conformations.more » « less
-
Abstract Fusobacterium varium has been generally overlooked in cattle rumen microbiome studies relative to the presumably more abundant liver abscess-causing Fusobacterium necrophorum. However, F. varium was found to be more abundant in the rumen fluid of cattle and under culture conditions tailored to enrich F. necrophorum. Using near-full length 16S ribosomal ribonucleic acid sequencing, we demonstrate that F. varium grows under restrictive conditions commonly used to enumerate F. necrophorum, suggesting that previous F. necrophorum abundance assessment may have been inaccurate and that F. varium may be an underestimated member of the ruminal bacterial community. Fusobacterium varium were not as susceptible as F. necrophorum to in-feed antibiotics conventionally used in feedlots. Exposure to tylosin, the current gold standard for liver abscess reduction strategies in cattle, consistently hindered growth of the F. necrophorum strains tested by over 67% (P < 0.05) relative to the unexposed control. In contrast, F. varium strains were totally or highly resistant (0%–13% reduction in maximum yield, P < 0.05). Monensin, an ionophore antibiotic, had greater inhibitory activity against F. necrophorum than F. varium. Finally, preliminary genomic analysis of two F. varium isolates from the rumen revealed the presence of virulence genes related to those of pathogenic human F. varium isolates associated with active invasion of mammalian cells. The data presented here encourage further investigation into the ecological role of F. varium within the bovine rumen and potential role in liver abscess development, and proactive interventions.more » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1126/science.adl6163
