Total Synthesis of Hapalindole‐Type Natural Products

Abstract

A unified and bioinspired oxidative cyclization strategy was used in the first total syntheses of naturally occurring 12-epi-hapalindole Q isonitrile, hapalonamide H, deschloro 12-epi-fischerindole I nitrile, and deschloro 12-epi-fischerindole W nitrile, as well as the structural revision of the latter. Hapalindoles H and Q were also synthesized.

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

“…Hapalindole H ( 1 ) acts as a fungicide and also inhibits growth of Staphylococcus aureus , Staphylococcus epidermidis and Staphylococcus pyogenes . Up to now, only two total syntheses of (±)‐hapalindole H are reported in the literature ,. The first total synthesis was achieved by Natsume and co‐workers in 1990 and recently the Li group reported another synthesis using bioinspired oxidative cyclization reaction.…”

Total Synthesis of Rubriflordilactone B

“…[1][2][3] Thecombination of 6p electrocyclization and oxidative aromatization for constructing multisubstituted arenes is of significant advantage from the following aspects:1 )strong driving force,2 )nof unctionalization (e.g., halogenation or metalation) required, 3) separating stereochemical problems from connectivity issues,4 )eliminating torquoselectivity issues, and 5) enhanced convergence.T hus,s uch strategies were creatively applied by an umber of groups in synthesizing natural products containing multisubstituted arenes, [4,5] which recently inspired us to explore this area. [6,7] However, the geometrically controlled formation of the prerequisite triene substrates is ac onsiderable challenge for executing the electrocyclization strategy.P artial-hydrogenation reagents (e.g.,L indlar catalyst, diazene,a ctivated Zn) suffer from incompatibility issues with functionalized diene-ynes and result in poor yields of the desired cis-trienes.P recursors of penta-and hexasubstituted arenes pose even greater difficulties in controlling the geometry of the more substituted olefin substrates.…”

Inverse γ‐Turn‐Inspired Peptide: Synthesis and Analysis of Segetalin A Indole Hemi­aminal

“…[11] The structure of native segetalin A has been well studied by crystal-structure analysis and in solution by NMR spectroscopy. [12,13] In the solid state, segetalin A is characterized by two β turns, one type I (Trp 4 and Ala 5 ) and one type VI (Val 1 and Pro 2 ) with a cis-Pro bond. [12] The structure is fixed by two transannular hydrogen bonds formed between Gly 6 and Val 3 , which results in an overall antiparallel β-sheet structure.…”

“…[1][2][3] A host of natural products contain the indole core in the form of alkaloids and tryptophan derivatives, which creates new challenges for synthetic chemistry and offers new features and surprising reactivity. [4] Indole hemiaminals, which have already proved their antitumor properties in the inhibition of tubuline polymerization, are also interesting as structural motifs. [5,6] In peptide drugs, the indole skeleton is represented by the side chain of tryptophan and is based on the slight reactivity of the indole NH group; this functional group will not react during conventional peptide synthesis.…”