Synthesis of Necatorone

A Biomimetic Approach to the Discorhabdin Alkaloids: Total Syntheses of Discorhabdins C and E and Dethiadiscorhabdin D

“…The most problematic part of the proposal is the postulated 1,6-addition of the enolate to the nitrogen of the quinonimine, leading to the p -aminophenol 45 and creating the crucial C−N bond. However, this speculative step is precedented in a key step in the Steglich synthesis of nectarone 8 …”

Synthesis of 1-(2-Aminophenyl)isoquinolines and the Biological Activity of Their cis-Dichloro Platinum(II) Complexes

“…6,7-Dimethoxy-1-(5-methoxy-2-nitrophenyl)-3,4-dihydroisoquinoline (8b). The title compound was prepared from amide 7b 16 (64.0 g, 178 mmol) according to the general procedure B. Recrystallization of the crude product from acetone/hexanes/MeOH yielded a yellow powder (56.9 g, 93%): mp 138−139 °C; IR (KBr) 3035 (w), 1605 (m), 1588 (s), 1570 (m), 1515 (s), 1405 (m), 1335 (s), 1295 (m), 1265 (m), 1242 (s), 1122 (m), 1080 (s), 1000 (w), 752 (w) cm -1 ; 1 H NMR (90 MHz, CDCl 3 ) δ 2.83 (t, J = 6.6 Hz, 2H), 3.58 (s, 3H, OCH 3 ), 3.82 (t, J = 6.6 Hz, 2H), 3.87 (s, 6H, OCH 3 ), 6.32 (s, 1H), 6.77 (s, 1H), 6.91−7.11 (m, 2H), 8.08 (d, J = 9.6 Hz, 1H); 13 C NMR (23 MHz, CDCl 3 ) δ 25.5 (C-4), 46.8 (C-3), 56.2 (OCH 3 ), 56.3 (2C, OCH 3 ), 109.5 (CH), 110.7 (CH), 115.5 (CH), 115.7 (CH), 121.2 (C), 127.2 (CH), 131.9 (C), 136.2 (C), 141.1 (C), 147.8 (C), 152.3 (C), 163.9 (C), 165.8 (C); EI-MS m / z (%) = 342 (100) [M + ], 312 (26), 299 (26), 281 (30), 269 (21). Anal.…”

“…Since imines of ortho -donor-substituted benzaldehydes are weak electrophiles and may not be cyclized under classical Pictet−Spengler conditions, all 1-(2-aminophenyl)-1,2,3,4-tetrahydroisoquinolines were synthesized on a highly efficient modified route. The dihydroisoquinolines were obtained by Bischler−Napieralski reactions.…”

Aza-Annulation Strategies in Alkaloid Total Synthesis

“…Another quinolone synthesis that involved a 1,6-addition on an iminoquinone was discovered by Steglich and coworkers. 25 Necatorone (23) is a highly mutagenic compound isolated from the toadstool Lactarius necator by the same research group. 26 The synthesis of necatorone readily delivered advanced intermediate 24 via the Bischler-Napieralski reaction and subsequent reduction of the nitro group to the amine (Scheme 9).…”