Anti-AIDS agents 73: Structure–activity relationship study and asymmetric synthesis of 3- O-monomethylsuccinyl-betulinic acid derivatives

Abstract

3- O-3′(or 2′)-Methylsuccinyl-betulinic acid (MSB) derivatives were separated by using recycle HPLC. The structures of four isomers were assigned by NMR and asymmetric synthesis. 3- O-3′ S-Methylsuccinyl-betulinic acid (3′ S-MSB, 4) exhibited potent anti-HIV activity with an EC 50 value of 0.0087 μM and a TI value of 6.3 × 10 3, which is comparable to the data for bevirimat (DSB, PA-457), a current clinical trials drug that was also derived from betulinic acid. The anti-HIV potency of 4 was slightly better than that of AZT.