Enantiospecific Total Syntheses of (+)‐Hapalindole H and (−)‐12‐epi‐Hapalindole U

Abstract

Enantiospecific total syntheses of (+)-hapalindole H and (-)-12-epi-hapalindole U as well as the formal syntheses of (+)-hapalindole Q and (+)-12-epi-fischerindole U isothiocyanate have been described. Key steps of our approach feature expedient, highly regio- and diastereoselective Lewis acid catalyzed Friedel-Crafts reaction of indole with cyclic allylic alcohols and intramolecular reductive Heck reaction. Efficiency of the synthetic route also relies on an alkynyl aluminate complex driven regioselective nucleophilic epoxide opening from a sterically hindered site.

Control of Stereoselectivity in Diverse Hapalindole Metabolites is Mediated by Cofactor‐Induced Combinatorial Pairing of Stig Cyclases

“…In the ambiguine‐producing strain F. ambigua UTEX 1903, FamC1 is known to generate 3 a . It is important to note that Dethe and co‐workers recently reported the structure of synthetic (−)‐12‐ epi ‐hapalindole U, and our optical rotation of (+)‐8.3 is consistent with the stereochemistry of natural product 3 a as C10 S , 11 R , 12 S , and 15 S . As expected, the product of FamC1 was reconfigured to 2 a by adding FamC4 (Figure ).…”

Intramolecular Heck Reaction in Total Synthesis of Natural Products: An Update

“…Compound 61 was then transmuted to another natural product hapalonamide H ( 62 ) in one step. In 2018, Dethe et al [25b] . used intramolecular Heck reaction as an important step to achieve the total synthesis of (+)‐hapalindole H ( 61 ) and its C12‐epimer ( 65 ).…”

Silver Salt-Mediated Allylation Reactions Using Allyl Bromides

“…13 3-(Cyclohex-2-en-1-yl)-1H-indole (5c). 16 Yield: 82%, 48.5 mg. Purified by flash column chromatography through silica gel (dichloromethane/methanol, 25:1). 1 H NMR (500 MHz, CHCl 3 ): δ 7.87 (br.…”