Dolutegravir, cabotegravir, and bictegravir are three integrase inhibitors, which were used for HIV-1 in the clinic. In this paper, a continuous three-step synthetic strategy was developed to prepare dolutegravir, cabotegravir, and bictegravir in a better yield, compared to the initial step-by-step procedure. Different solvents, temperature, and times were optimized. In the course of industrial production of active pharmaceutical ingredient (API), this three-step synthetic protocol has several advantages, including low cost, time-saving, and better yield. This process was successfully scaled up to tens of grams. GRAPHICAL ABSTRACT

The aminophosphinoylation of alcohols with amines and H-phosphine oxides provides an efficient and mild approach to access various α-aminoalkylphosphine oxides in good yields with good tolerance of functional groups using H₂O as a clean solvent.

A facile synthetic method was developed for a novel acid-sensitive camptothecin norcantharidin acid ester derivative I . The total yield can reach 71%. This method provides several advantages, including high yield and simple working procedure for the synthesis of analogues. The new synthetic compound I has been shown to exhibit better solubility and similar activity against tumour cell lines.