Modifications to the Vilsmeier‐Haack formylation of 1,4‐dimethylcarbazole and its application to the synthesis of ellipticines

Abstract

An improved method for the preparation of 3‐formyl‐1,4‐dimethylcarbazole, a key intermediate in the synthesis of ellipticine, is presented. Conditions of the Vilsmeier‐Haack reaction have been modified to facilitate the production of 3‐formyl‐1,4‐dimethylcarbazole as a major product leading to an overall improvement in yield of ellipticine from 3% to 14%. This approach was also applied to the synthesis of 6‐methylellipticine and 9‐methoxyellipticine. J. Heterocyclic Chem., (2011).

Indole alkaloid ellipticine as efficient multitarget compound

“…The most convenient synthetic pathway to ellipticine (5,11-dimethyl-6H-pyrido[4,3-b]carbazole, 10) was proposed by Cranwell and Saxton [21] with later modifications [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44] (see Figure 2). We supposed that it might be possible to further improve the overall procedure by improving the synthesis of 1,4-di-methylcarbazole 2, the Vilsmeier-Haack formylation, and the cyclization steps.…”

“…Generally, synthetic strategies leading to the target molecule are classified according to assembly of the last ring as B, C, D, and B + C types (Passemar et al, 2011) [10] (see Figure 1). Among the different synthetic routes available [21][22][23][24][25][26][27][28][29], the method originally proposed by Cranwell and Saxton appears to be the most practical one [21,30]. It consists of a five-stage ''D-type'' procedure starting from appropriately substituted indoles or carbazoles.…”

Inhibitory Properties of Aldehydes and Related Compounds against Phytophthora infestans—Identification of a New Lead

“…m.p 205–206 °C (Lit. m.p 202–204 °C) [ 61 ]; IR ν max /cm −1 : 2921, 2852, 1588, 1476, 1449, 1241, 1102, 806; δ H (300 MHz, DMSO- d 6 ): 3.03 (3H, s, CH 3 -5), 3.19 (3H, s, CH 3 -11), 4.13 (3H, s, NCH 3 ), 7.31 (1H, overlapping ddd, J 8.0, 6.4, 1.5, H-9), 7.58 (1H, dd, J 8.0, 1.5, H-8), 7.62 (1H, d, J 1.5, H-7), 7.99 (1H, d, J 6.0, H-4), 8.37 (1H, d, J 8.0, H-10), 8.45 (1H, d, J 6.0, H-3), 9.68 (1H, s, H-1); m / z (ESI + ) 261 [(M + H) + , 100%].…”

Total Synthesis of Olivacine and Ellipticine via a Lactone Ring-Opening and Aromatization Cascade

“…Since 1960s, total synthesis of olivacine and ellipticine has been a subject of many publications, as discussed in several review articles. ,,,− The majority of the methods for their syntheses rely on the late-stage D-ring cyclization, − whereas the late-stage C-ring − and B-ring cyclization strategies have been rarely reported. In their report in 1962, Cranwell and Saxton presented an effective and concise synthesis of ellipticine through the late-stage cyclization of the D-ring from lower rim .…”

“…In their report in 1962, Cranwell and Saxton presented an effective and concise synthesis of ellipticine through the late-stage cyclization of the D-ring from lower rim . Cranwell–Saxton synthesis of ellipticine was later frequently utilized for the generation of ellipticine derivatives. , However, the scope of Cranwell–Saxton methodology is limited to the synthesis of ellipticine and its some derivatives because it depends on the use of hexane-2,5-dione as the starting material. On the other hand, Schmutz and Wittwer as well as Wenkert and Dave introduced the late-stage cyclization of D-ring from the upper rim for the synthesis of olivacine, in early 1960s.…”