Total synthesis of marine natural products without using protecting groups.
The field of organic synthesis has made phenomenal advances in the past fifty years, yet chemists still struggle to design synthetic routes that will enable them to obtain sufficient quantities of complex molecules for biological and medical studies. Total synthesis is therefore increasingly focused on preparing natural products in the most efficient manner possible. Here we describe the preparative-scale, enantioselective, total syntheses of members of the hapalindole, fischerindole, welwitindolinone and ambiguine families, each constructed without the need for protecting groups--the use of such groups adds considerably to the cost and complexity of syntheses. As a consequence, molecules that have previously required twenty or more steps to synthesize racemically in milligram amounts can now be obtained as single enantiomers in significant quantities in ten steps or less. Through the extension of the general principles demonstrated here, it should be possible to access other complex molecular architectures without using protecting groups.
Baran
Phil S
PS
Department of Chemistry, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037, USA. pbaran@scripps.edu
Maimone
Thomas J
TJ
Richter
Jeremy M
JM
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods*; D000458:Cyanobacteria / Q000737:chemistry; D026121:Indole Alkaloids; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D009570:Nitriles / Q000138:chemical synthesis / Q000737:chemistry; D012623:Seawater / Q000382:microbiology
D000470:Alkaloids; D001688:Biological Products; D026121:Indole Alkaloids; D007211:Indoles; D009570:Nitriles; C518616:ambiguine H; C491991:fischerindole; C518617:hapalindole U; C507638:welwitindolinone A