Preparation of Tricyclic Analog as CDE Ring Model of Renieramycin Marine Natural Product by Novel Photo-Induced Transformation of 6-Methoxy-1,2,3,4-Tetrahydroisoquinoline-5,8-dione

Abstract

2-Acetyl-6-[(benzyloxy)methyl]-9-methoxy-8-methyl-11,11adihydro-2H-pyrazino[1,2-b]isoquinoline-1,4,7,10(3H,6H)-tetraone (11a) was prepared as the CDE ring model of renieramycins, and its novel photo-induced transformation was demonstrated to construct a 1,3-dioxol ring. PCC (2.0 eq.) CH 2 Cl 2 rt, 1.5 h Me HO OMe O OBn 19 MeO Me OBn HN NAc O O 14 (1.0 eq.) 1 M t BuOK/ t BuOH (1.2 eq.) CH 2 Cl 2 , rt, 2.5 h 24 81% H 2 , 10% Pd-C EtOH : DMF (1 : 1) rt, 1.5 h 98% MeO Me OH HN NAc O 25 O 91% 2 steps from 21 H 2 , Pd/C, EtOH, DMF, 94%

Photochemical reaction of renieramycins and evaluation of cytotoxicity against lung cancer cells

“…Structural comparison of saframycins, ecteinascidin 743 and renieramycins (1) Figure 8 Semi-synthesis of renieramycins derivative from renieramycin M (27) Table 1 Cytotoxicity of potent renieramycin M derivatives against H292 and H460 non-small-cell lung cancer cell lines (16,29) Therefore, it is interesting to modify the renieramycin M (1) structure to contain the [1,3]-dioxole ring by using specific reaction such as photochemical reaction, which was recently reported (Figure 9) (35,36) . The synthesis of [1,3] 2.3 ± 0.4 5.1 ± 0.5 was succeeded by using the photo-induced ring-closing reaction.…”

“…Table 1 H NMR (400 MHz) spectral data of compound 6, 7 and 10 in CDCl 3 (44) .......... 1 Table 13 C NMR (100 MHz) spectral data of compound 6, 7 and 10 in CDCl 3 (44) [1,3]-dioxole ring by photo-induced ring-closing reaction of quinone moiety (35,36) [1,3]-dioxole ring by hydrogenation of the quinone group (37,38) ...…”

“…The synthesis of [1,3] 2.3 ± 0.4 5.1 ± 0.5 was succeeded by using the photo-induced ring-closing reaction. The photochemical reaction and mechanism were revealed and applied to the total synthesis of ecteinascidins and renieramycin T (4) marine natural products (35) . Based on the reported data, synthesis of [1,3]-dioxole using the photo-induced ring-closing reaction with one-pot acetylation gave the improved reaction yield (Figure 9 [1]) (35) .…”

“…The photochemical reaction and mechanism were revealed and applied to the total synthesis of ecteinascidins and renieramycin T (4) marine natural products (35) . Based on the reported data, synthesis of [1,3]-dioxole using the photo-induced ring-closing reaction with one-pot acetylation gave the improved reaction yield (Figure 9 [1]) (35) . In addition, using tetrahydrofuran (THF) as a solvent under photochemical reaction with blue light showed the optimum yields (Figure 9 [2] and [3]) (36) .…”

“…This treatment facilitated the formation of a fivemembered ring, producing compound 21 with a yield of 44% (38) (Figure 10). Figure 9 Synthesis of [1,3]-dioxole ring by photo-induced ring-closing reaction of quinone moiety (35,36) Figure 10 Synthesis of [1,3]-dioxole ring by hydrogenation of the quinone group (37,38) Recently, Yokoya and his research team reported on the photoredox reactions of compounds in the 1,2,3,4-tetrahydroisoquinoline group, achieving 5hydroxy-tetrahydroisoquinol [1,3]-dioxoles in excellent yields (39) . They also adjusting the concentration of the starting material to 2 or 4 mM, the reaction time significantly decreased to a range of 3 to 8 hours (39) .…”