Base-Promoted Nucleophilic Phosphorylation of Benzyl Fluorides via C(sp3)-F Cleavage.

Herein, a transition-metal-free phosphorylation of benzyl fluorides with P(O)-H compounds is disclosed. In the presence of tBuOK, various benzyl fluorides react with P(O)-H compounds to produce the corresponding benzyl phosphine oxides, phosphinates, and phosphonates in good to high yields. This base-promoted phosphorylation reaction offers a facile and general strategy for the construction of a C(sp3)-P bond.

Ni-catalyzed C-F activation to construct C-P bond with P-P(O) and P(O)OR mediation.

Here we developed an efficient Ni-catalyzed C-F bond phosphorylation of aryl fluorides via the crucial intermediates of P-P(O) and P(O)OR. P-P(O) mediated organophosphorus generation is observed for active aryl fluorides, whereas inactive aryl fluorides can also be activated and phosphorylated via a P(O)OR-mediated pathway, which is barely reported yet. Facile scale-up to the gram level and the upgrading of the bioactive molecule make this protocol to have promising applications in synthetic chemistry.

Cholesterol and saturated fatty acids synergistically promote the malignant progression of prostate cancer.

The excessive accumulation of saturated fatty acids and cholesterol have been linked to prostate cancer (Pca). Here, we found that lipoproteins, apolipoproteins, triglycerides and free fatty acids are significantly higher in the peripheral blood of prostate cancer patients than in non-cancer patients. Furthermore, the expression of ACC1, FASN and HMGCR is significantly higher in prostate cancer tissues than that in non-cancer tissues, and positively correlated with the gleason score. Using genetically engineered mouse models, we found that in a mouse model of high grade prostatic intraneoplasia (HGPIN), a combination of fatty acid synthase (FASN) overexpression and cholesterol efflux pump (Abca1) knockout resulted in the progression of prostatic intraneoplasia (PIN) to invasive PCa with 100% penetrance, as well as an increase in prostate cancer stem cell (PCSC)population, accompanied by activation of PGE2 and TGF-ß signaling pathway. Our study suggests that the steady rise in prostate cancer incidence and mortality among Chinese population during the last several decades may be attribute to a combinational effect of fatty acid and cholesterol, and reduction in dietary fat and cholesterol intake could slow down the progression from occult lesions to prostate cancer.