Asymmetric Total Syntheses of Aetheramides and Their Stereoisomers: Stereochemical Assignment of Aetheramides.
The concise total syntheses of the potent HIV inhibitors aetheramides A and B (IC50 values of 15 and 18 nM), as well as three pairs of their stereoisomers, were achieved, which allowed the complete stereochemical assignment of aetheramides for the first time. With a longest linear sequence of 15 steps, the convergent, fully stereocontrolled route provided aetheramides A and B in 5.3% and 3.6% yields, respectively. The synthetic strategy features efficient Stille coupling for macrocyclization, asymmetric aldol reactions to establish the ambiguous stereochemistries at C-17 and C-26, and implementation of mild conditions to avoid the epimerization of the sensitive polyketide moiety and the migration of the labile lactone.
School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University , 55 Daxuecheng South Road, Shapingba, Chongqing 401331, P. R. China.
Na
N
Qi
School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University , 55 Daxuecheng South Road, Shapingba, Chongqing 401331, P. R. China.
Srinivasa Rao
SR
Allu
School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University , 55 Daxuecheng South Road, Shapingba, Chongqing 401331, P. R. China.
Zhanlong
Z
Wang
School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University , 55 Daxuecheng South Road, Shapingba, Chongqing 401331, P. R. China.
Qiang
Q
Liu
School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University , 55 Daxuecheng South Road, Shapingba, Chongqing 401331, P. R. China.
Jian
J
Guo
School of Pharmaceutical Sciences and Innovative Drug Research Centre, Chongqing University , 55 Daxuecheng South Road, Shapingba, Chongqing 401331, P. R. China.
Yun
Y
He