A divergent approach to the synthesis of the yohimbinoid alkaloids venenatine and alstovenine.
The yohimbinoid alkaloids continue to receive considerable attention from the synthetic community because of their interesting chemical structures and varied biological activity. Although there are several elegant syntheses of certain members of this group of alkaloids, a truly unified approach has yet to be developed. In short, general approaches to this compound class are hampered by a lack of complete control in setting the C(3) stereocentre at a late stage. Herein, we report that a functionalized hydrindanone enables a divergent strategy that builds on existing precedent to address this long-standing challenge. Utilizing an aminonitrile intermediate, the stereochemistry at C(3) of the yohimbinoid skeleton can be controlled effectively in a Pictet-Spengler reaction. We applied this approach to the first total syntheses of the C(3) epimeric natural products venenatine and alstovenine.
Department of Chemistry, University of California, Berkeley, Berkeley, California                 94720, USA.
Terry P
TP
Lebold
Jessica L
JL
Wood
Josh
J
Deitch
Michael W
MW
Lodewyk
Dean J
DJ
Tantillo
Richmond
R
Sarpong
D000470:Alkaloids / Q000138:chemical synthesis*; D006358:Hot Temperature; D008958:Models, Molecular; D015394:Molecular Structure; D013237:Stereoisomerism; D014050:Toluene; D015016:Yohimbine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry*
D000470:Alkaloids; C579638:alstovenine; C425296:venenatine; D015016:Yohimbine; D014050:Toluene