Tandem Reductive Cyclization–Dehydration Approach for the Synthesis of Cryptolepine Hydroiodide and Its Analogues

Abstract

A new and convenient synthesis of the indoloquinoline alkaloid cryptolepine hydroiodide is described through a tandem reductive cyclization–dehydration approach. This methodology employs a C–C bond formation through the C‐2 lithiation of a benzenesulfonyl‐protected indole and a C–N bond formation through a nitrene intermediate, which is produced from different organophosphorus reagents, to give a fused tetracyclic compound. The versatility of this method is demonstrated by the syntheses of a series of cryptolepine salts with substituents on the indole as well as the quinoline ring.

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…A four-step synthesis of 59 from N-sulfonylindole was developed through a tandem reductive cyclization/dehydration reaction followed by methylation (Scheme 9). 34 The total synthesis of isocryptolepine (60) was accomplished by Hibino's and Butin's groups. Butin's approach featured a facile construction of the indole ring by the acidinduced reaction of 2-furylaniline with 2-nitrobenzaldehyde followed by the reductive cyclization of 2-nitrophenylindole (Scheme 10).…”

A Compilation of Synthetic Strategies to Access the Most Utilized Indoloquinoline Motifs

“…Interestingly, under different nitrene generation conditions employing P(OEt) 3 in solvent‐free conditions at 150–160 °C, the same substrate was converted to indoloquinoline 2 in 26% along with indoloquinoline 1 in 8% (pathway D, Scheme 16). [40] …”

“…Interestingly, under different nitrene generation conditions employing P(OEt) 3 in solvent-free conditions at 150-160 °C, the same substrate was converted to indoloquinoline 2 in 26% along with indoloquinoline 1 in 8% (pathway D, Scheme 16). [40] In addition, cyclocondensation of 2-hydroxymethylenecycloketone 72 and corresponding nitroenamines 73 could lead to the formation of 3-nitropyridines 74. Then, cyclization reactions were performed using Mo(VI)-catalyzed Cadogan reaction to afford a series of δ-carbolines 75 with a fused cyclohexane ring which was then oxidized using Pd on charcoal under heating conditions to give the desired product 2 (Scheme 17).…”

Intramolecular trapping of an iminium salt: rapid construction of quindoline derivatives

“…31 A series of elegant methods for quindoline synthesis have been reported, however, they generally suffer from disadvantages such as requiring multiple steps, giving low yields, and requiring harsh reaction conditions. [32][33][34][35][36][37] Therefore, more efficient, convenient methods for quindoline synthesis remain elusive. Among the numerous known methods, those involving the efficient construction of the pyridine ring have been the focus of considerable attention (Scheme 1a).…”