Enantiospecific total synthesis of the hapalindoles, fischerindoles, and welwitindolinones via a redox economic approach.
Full details are provided for the total synthesis of several members of the hapalindole family of natural products, including hapalindole Q, 12-epi-hapalindole D, 12-epi-fischerindole U, 12-epi-fischerindole G, 12-epi-fischerindole I, and welwitindolinone A. Use of the recently developed direct indole coupling enabled an efficient, practical, scalable, and protecting-group-free synthesis of each of these natural products. The original biosynthetic proposal is reviewed, and a revised biosynthetic hypothesis is suggested, validated by the above syntheses. The syntheses are also characterized by an adherence to the concept of "redox economy". Analogous to "atom economy" or "step economy", "redox economy" minimizes the superfluous redox manipulations within a synthesis; rather, the oxidation state of intermediates linearly and steadily increases throughout the course of the synthesis.
Richter
Jeremy M
JM
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Ishihara
Yoshihiro
Y
Masuda
Takeshi
T
Whitefield
Brandon W
BW
Llamas
Tomás
T
Pohjakallio
Antti
A
Baran
Phil S
PS
D000470:Alkaloids / Q000096:biosynthesis / Q000138:chemical synthesis*; D040761:Biomimetic Materials / Q000737:chemistry; D026121:Indole Alkaloids; D007211:Indoles / Q000138:chemical synthesis*; D009570:Nitriles / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D013237:Stereoisomerism
D000470:Alkaloids; D026121:Indole Alkaloids; D007211:Indoles; D009570:Nitriles; C491991:fischerindole; C438931:hapalindole Q; C507638:welwitindolinone A