A detailed account of an asymmetric Nazarov cyclization that leads to α‐hydroxycyclopentenones bearing either vicinal, all‐carbon quaternary centers, or vicinal quaternary and tertiary centers is given. The all‐aliphatic examples represent the greatest challenge, as the dienone starting materials are not activated toward cyclization by an aryl group. The rational design and optimization of the substrates in parallel with optimization of the chiral Brønsted acid catalyst is also described, as well as a series of diastereoselective transformations of a fully substituted cyclopentenone product.

We have developed robust, operationally simple syntheses of fluorenes and of dibenzo [g,p]chrysenes through oxidative cascade processes. These structures that are commonly encountered in optoelectronic materials, dyes, and pharmaceutical products are accessible from 1,4-dioxaspiro[4.5]decan-8-one. The reactions are conducted open to air with inexpensive, safe CuBr 2 or CuCl 2 .

A convergent synthesis of dibenzochrysenes and diindenochrysenes that proceeds from difluorofluorenes and acetoxyenone 15 has been used to prepare 5,6,11,12-tetrabromosemibuckminsterfullerene (31). The synthesis is highly modular and is distinguished by proceeding through an unsymmetrical intermediate. Our work will enable the straightforward preparation of semibuckminsterfullerenes from diindenochrysenes that lack bilateral symmetry using common reagents and nonpyrolytic conditions.

Dysregulated gene expression programs and redox and metabolic adaptations allow cancer cells to survive under high oxidative burden. These mechanisms also represent therapeutic vulnerabilities. Using triple-negative breast cancer (TNBC) as a model, we show that compared to normal human breast epithelial cells, the TNBC cells, MDA-MB-231 and MDA-MB-468 that harbor constitutively active STAT3 also express higher glucose-6-phosphate dehydrogenase (G6PD), thioredoxin reductase (TrxR)1, NADPH, and GSH levels for survival. Present studies discover that the natural product, R001, targets these adaptation mechanisms. Treatment of TNBC cells with R001 inhibited constitutively active STAT3, STAT3-regulated gene expression, and the functions of G6PD and TrxR1. Consequently, in the TNBC, but not normal cells, R001 suppressed GSH levels, but raised NADPH levels, reflective of a loss of mitochondrial respiration and which led to reactive oxygen species (ROS) induction, all of which led to loss of viable cells and inhibition of anchorage-dependent and independent growth. R001 treatment further led to early pyroptosis and late DNA damage, cell cycle arrest, and apoptosis only in the TNBC cells. Oral administration of 5 mg/kg R001 inhibited MDA-MB-468 xenografts growth in mice, with reduced pY705-STAT3, G6PD, TrxR1, and GSH levels. R001 serves as a therapeutic entity that targets the vulnerabilities of TNBC cells to inhibit tumor growth in vivo.

A practical synthesis of 1,8-difluorofluorenone and of its (2,7)-dibromo and (2,4,5,7)-tetrabromo derivatives has been developed. Fluorinated fluorenones are the starting materials for polyhalogenated dibenzochrysenes as well as for geodesic hydrocarbons....