Total synthesis and preliminary biological evaluation of cis-solamin isomers.
An efficient total synthesis of cis-solamin (1) has been achieved in 21% overall yield and with a longest linear sequence of just 11 steps from aldehyde 8. A key feature of the approach was the use of asymmetric permanganate-promoted oxidative cyclization to introduce four of the five required stereocenters in a single step. The use of robust and chemoselective methodology meant that the use of protecting groups could be avoided during the assembly of cis-solamin (1) from the three fragments 23, 6, and 4. The methodology was also applied to the synthesis of three further cis-solamin isomers 2, ent-1, and ent-2. Cytotoxicity and hemolytic properties of cis-solamin isomers and synthetic intermediates are reported.
Cecil
Alex R L
AR
Department of Chemistry, The University of Southampton, Highfield, UK.
Hu
Yulai
Y
Vicent
María J
MJ
Duncan
Ruth
R
Brown
Richard C D
RC
D000818:Animals; D001558:Benzethonium / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003500:Cyclization; D004852:Epoxy Compounds / Q000138:chemical synthesis; D020128:Inhibitory Concentration 50; D007536:Isomerism; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D004852:Epoxy Compounds; D001558:Benzethonium