2 research outputs found
Rotationally Hindered Biphenyls and Terphenyls: Synthesis, Molecular Dynamics, and Configurational Assignment
Sterically hindered
naphthalene-substituted biphenyls and terphenyls
were synthesized in good yields, by Michael addition of a conjugate
base of core-substituted phenylacetones to substituted 2-oxo-2<i>H</i>-pyran-3-carbonitriles at room temperature under alkaline
conditions. These diversely functionalized benzenes (1,2-teraryls
or 1,3-teraryls), bearing naphthyl and substituted aryl rings, show
the phenomenon of atropisomerism, with one or two stereogenic biaryl
axes. The resolution of the respective four atropisomers of the naphthalene-substituted
biphenyls and terphenyls bearing 1,2-type or 1,3-type chiral biaryl
axes was achieved by HPLC on a chiral phase. The absolute stereostructures
of <b>6a</b> and <b>9a</b> were determined by the combination
of experimental electronic circular dichroism (ECD) investigations
and quantum-chemical circular dichroism (QC-CD) calculations. For
the atropisomerization of (1<i>M</i>,6<i>M</i>)-<b>6a</b> and (1<i>M</i>,5<i>M</i>)-<b>9a</b> to their (<i>M</i>,<i>P</i>)- and (<i>P</i>,<i>M</i>)-diastereomer, respectively, the possible
transition states were investigated and the interconversion barriers
(Δ<i>G</i><sup>‡</sup>) were theoretically
predicted. This study provides a general protocol for the synthesis,
resolution, and stereochemical characterization of rotationally hindered
naphthalene-substituted biphenyls and terphenyls. The strategy may
be applied to investigate other, similarly hindered biaryl or teraryl
systems either derived from natural sources or prepared through synthetic
approaches
Uncertainties and controversies in axillary management of patients with breast cancer
The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 250 breast surgeons, patient advocates and radiation oncologists from 60 countries. Subsequently, a global virtual consensus panel considered available data, ongoing studies and resource utilization. It agreed that research should no longer be prioritized for standardization of axillary imaging, de-escalation of axillary surgery in node-positive cancer and risk evaluation of modern surgery and radiotherapy. Instead, expert consensus recommendations for clinical practice should be based on current evidence and updated once results from ongoing studies become available. Research on de-escalation of radiotherapy and identification of the most relevant endpoints in axillary management should encompass a meta-analysis to identify knowledge gaps, followed by a Delphi process to prioritize and a consensus conference to refine recommendations for specific trial designs. Finally, treatment of residual nodal disease after surgery was recommended to be assessed in a prospective register.</p