IBX facilitated the reaction of β-enamino esters with allylic alcohols affording a direct, one-pot and metal free synthesis of functionalized pyridines including 2-substituted nicotinic acids, densely substituted pyridines and precursors of azafluorenones. The methodology also afforded the racemic pyridine core of cyclothiazomycin.

The efficacy of paclitaxel (PTX) is limited due to its poor solubility, poor bioavailability, and acquired drug resistance mechanisms. Designing paclitaxel prodrugs can improve its anticancer activity and enable formulation of nanoparticles. Overall, the aim of this work is to improve the potency of paclitaxel with prodrug synthesis, nanoparticle formation, and synergistic formulation with lapatinib. Specifically, we improve potency of paclitaxel by conjugating it to α-tocopherol (vitamin E) to produce a hydrophobic prodrug (Pro); this increase in potency is indicated by the 8-fold decrease in half maximal inhibitory concentration (IC₅₀) concentration in ovarian cancer cell line, OVCA-432, used as a model system. The efficacy of the paclitaxel prodrug was further enhanced by encapsulation into pH-labile nanoparticles using Flash NanoPrecipitation (FNP), a rapid, polymer directed self-assembly method. There was an 1100-fold decrease in IC₅₀ concentration upon formulating the prodrug into nanoparticles. Notably, the prodrug formulations were 5-fold more potent than paclitaxel nanoparticles. Finally, the cytotoxic effects were further enhanced by co-encapsulating the prodrug with lapatinib (LAP). Formulating the drug combination resulted in synergistic interactions as indicated by the combination index (CI) of 0.51. Overall, these results demonstrate this prodrug combined with nanoparticle formulation and combination therapy is a promising approach for enhancing paclitaxel potency.

Diels-Alder reaction of furan with electron-deficient 3-carbethoxycoumarins gave the Michael-type adducts obtained from the rearrangement of the intermediate Diels-Alder adducts, instead of the Diels-Alder cycloadducts. Trapping of the dipolar intermediate with electron-deficient aromatic aldehydes gave a one-pot access to fused furo[3,2-b]pyranochroman-2-ones with multiple stereogenic centers. Ring opening of the lactone moiety gave a facile route to generate diverse scaffolds.