Total Synthesis of Phaeantharine

Abstract

Mitte der fiinfziger Jahre wurde nach umfangreichen Untersuchungen im Arbeitskreis v. Bruchhausen')z) fiir das von Sant0.3~) isolierte Alkaloid Phaeantharin die Struktur 1 abgeleitet. Zusammen mit Weirich4) sollte diese Struktur durch Synthese bewiesen werden. Nachdem einige Vorarbeiten hierzu abgeschlossen waren, erhielten wir Kenntnis, dal3 ein hollandischer Arbeitskreis') aufgrund spektroskopischer Untersuchungen von Phaeantharin und Vergleichssubstanzen statt unserer Fonnell f i r Phaeantharin, die Formel 2 postulierte, in der sich anstelle der Etherbriicke im Isochinolinteil in 7'-Stellung eine Methoxygruppe befindet . OCH3 H,C-N\ 0 0 1 2 \ / OCH, Wir wollten daraufhin die Synthese von 2 in Angriff nehmen, und m a r sollte sie analog der geplanten Synthese von 14") nach Schema 1 erfolgen. Schema 1 BrBr

Bisbenzylisoquinoline Alkaloids

“…TLC: 0.37 (Si gel 60 PF254; EtOAc-iPrOH-NH4OH ([9:7:2]) (86) [a]25D: -7.6°(c=0.38, MeOH) (86) UV: 275,285 (86) 'H nmr: NCH3 2.60, N+0"CH3 3.32, OCH3 3.42 (2), 3.84(2), ArH 4.31 (2H)(d)(/= 10 Hz), 5.81 (2H) (dd) (/=2.7, 8.5 Hz), 6.27 (2H) (dd) (7=2.0, 8.5 Hz), 6.58 (2H) (dd) (7=2.7, 8.5 Hz), 7.10 (2H) (dd) (7=2.0, 8.5 Hz) (86) MS(EI): M+638(3), 622 (55), 607 (8), 313 (23), 312 (100), 311 (35), 204 (25), 190(15), 174(9) (86) MS(FD): M+638 (100), 622 (40) (86) SOURCES: Synclisia scabrida Miers (Menispermaceae) (86) DERIVATIVES: Cycleanine (Cycleanine N-0xide+H2S03) (tic, color reactions) (86) PREPARATION: Via oxidation (3% H202) of cycleanine tic (86) 233 N-DESMETHYLCYCLEANINE C37H40O6N2:608.2886 Type XX (R,R) 6,7,8*, 12+-6,7,8+, 12* MP: 102-103°(MeOH) (65) [o¡]32D: (65) nmr: NCH3 2.51, OCH3 3.40, 3.45, 3.80, 3.85, A1H 2.65-3.40 (m, 12H), 4.23 (m)(H-l), 4.62 (m) ( -1'), ArH 5.77 (dd) (1H) (7=2, 8 Hz) (H-13 or H-13'), 5.81 (dd) (1H) (7=2, 8 Hz) (H-13'or H-13), 6.25 (dd) (1H) (7=2, 8 Hz) (H-14 or H-14'), 6.30 (dd) (1H) (7= 2, 8 Hz) (H-14' or H-14), 6.54 (dd) (1H) (7=2, 8 Hz) (H-ll or H-ll'), 6.55 (s) (2H) H-5 and H-5'), 6.57 (dd) (1H) (7= 2, 8 Hz)(H-l 1' or H-ll), 7.03 (dd)(lH)(7=2, 8 Hz) (H-10 or H-10'), 7.23 (dd)(lH) (7=2, 8 Hz) (H-10' or H-10) (65) 13C nmr: 56.71 (C-1 or C-l'), 60.9 (C-1' or C-l), 42.66 (C-3 or C-3'), 44.84 (C-3' or C-3), 24.93 (C-4 or C-4'), 26.64 (C-4' or C-4), 128.73 (C-4a or C-4a'), 128.98 (C-4a' or C-4a), 108. C-5'), 109.56 (C-5'or C-5), 152.04 (C-6 or C-6'), 153-46 (C-6'orC-6), 139.14 (C-7 or C-7'), 140.26 (C-7' or C-7), 143.76 (C-8 or C-8'), 143.97 (C-8' or C-8), 125.36 (C-8a or C-8a'),…”

“…145.1 (C-8), 122.2(C-8a), 38.0(C-a), 119.9(C-9), 143.5 (C-10), 141.5 (C-ll), 152.3 (C-12), 101.5 (C-13), 121.7 (C-14), 64.1 (C-V), 44.9 (C-3'), 24.9 (C-4'), 128.1 (C-4a'X 112.0 (C-5'), 148.1 (C-6'), 149.1 (C-7'), 126.4 (C-8'), 128.1 (C-8a'X 42.3 (C-'), 133.1 (C-9'), 129.6 (C-10' 157.2 (C-l V), 120.6 (C-12'), 132.5 (C-13'), 133.1 (C-14'), 39.4 (N-2 NCH3), 40.1 (N-2' NCH3), OCH3 signals not reported (96) [Note: These assignments were based on the original structure proposed for thalibrunine (110) and not the revised structure (111)] 120 TILIAMOSINE (C36H3606N2:592.2573) MP: 167-170°( CHCI3/MeOH) (amorph.) (120) [a]25D: +267°(r=0.48, CHC13) (120) UV: 235 (sh) (4.70), 290 (3.98) NCH3 2.32, OCH3 3.83, 3.94, 3.98, ArH 6.66, 6.97 (d) (1H) <J=8.5 Hz), 7.00 (d) (1H) (/=8.5 Hz), 7.32 (dd)(lH) (/=2.2, 8.1 Hz), 7.35 (dd) (1H) (7=2.2, 8.5 Hz), 7.62(d)(lH) (1.8 Hz), 7.69 (d) (1H) (7=2.2 Hz), 8.13 (120) MS: M+ 592, 591, 366, 365, 351, 211, 183 (100) (120) DERIVATIVES: N, O-Diacetyltiliamosine (Tiliamosine+Ac20+pyridine) (120) MP: 182-184°( CHC13) (120) [a]25D: +423°(c=0.35, CHC13) (120) UV: 236 (sh) (4.59), 291 (3.79) (120) IR(KBr): 1765, 1645 (120) nmr: OCOCH3 2.13, NCH3 2.24, NCOCH3 2.24, OCH3 3.81 (s) (6H), 3.84, ArH 6.61, 6.79- 7.95 (m) (6H), 8.05 (120) MS: M+676, 634, 408, 393, 366, 365, 211, 183 (100) (120) 130 deriva...…”

β-Phenylethylamines and the isoquinoline alkaloids

“…or-Narcotinediol, on heating with potassium tbutoxide and benzophenone, has been found to give the base (69) rat her than the an hyd ro-diol, without racemization at the benzylic centre. I 50 14-Methoxy-8,13-dioxocanadine (70), on pyrolysis, has been found to give 35% of the ester (71) and 15% of the lactone (72), which has been N-methylated and reduced to (+-)-aand ( +)-p-hydrastine.IS1 P-Alkoxyphenylethylamines have been shown to react with (dimethylaminomethy1ene)phthalides to give phthalide-isoquinolines, which may be N-methylated; in this way, (*)-…”