Eine neue Synthese von Bufotenin und verwandten Oxy‐tryptaminen. 40. Mitteilung über Mutterkornalkaloide

Abstract

Es wird eine rationelle Synthese für das Bufotenin und andere ω‐N‐substituierte 5‐Oxy‐tryptamine angegeben. Folgende neue Verbindungen aus der Reihe der Oxy‐tryptamine werden beschrieben: 5‐Oxy‐ω‐N‐methyl‐tryptamin, 5‐Oxy‐ω‐N‐äthyl‐tryptamin, 5‐Oxy‐ω‐N, N‐diäthyl‐tryptamin, 5‐Oxy‐ω‐N‐β‐aminoäthyl‐tryptamin, N‐[β‐(5‐Oxy‐indolyl‐(3))‐äthyl]‐piperidin, sowie zwei Stellungsisomere des Serotonins, das 4‐Oxy‐tryptamin und das 6‐Oxy‐tryptamin.

Synthetic Studies of Psilocin Analogs Having Either a Formyl Group or Bromine Atom at the 5- or 7-Position.

“…1-tert-Butoxycarbonyl-4-tert-butoxycarbonyloxy-5-formyl-N,N-dimethyltryptamine (11) from 9 A solution of 9 (10.4 mg, 0.045 mmol), DMAP (5.6 mg, 0.046 mmol), and Boc 2 O (0.04 ml, 0.17 mmol) in CH 2 11) (42.2 mg, 0.13 mmol) was added to a solution of 1a (22.4 mg, 0.11 mmol) in CH 2 Cl 2 (3 ml) and AcOH (0.3 ml), and the mixture was stirred at room temperature for 5 h. After evaporation of the solvent under reduced pressure, the residue was column-chromatographed repeatedly on SiO 2 with CHCl 3 -MeOH-28% aq. NH 3 (46 : 5 : 0.5, v/v) to give quite unstable 15 (6.3 mg, 16%), a mixture (13.8 mg, 44%) of unstable 13 and 14 (in a ratio of 1 : 9, calculated by 1 H-NMR) and unreacted 1a (3.1 mg, 14%) in the order of elution.…”

“…The reaction mixture was filtered through SiO 2 to remove Pd-C and the filtrate was evaporated under reduced pressure to leave a crystalline solid, which was recrystallized from CHCl 3 -MeOH to give 22 (70.6 mg). The mother liquor was purified by p-TLC on SiO 2 , and the mixture was stirred at room temperature for 24 h. After addition of brine, the whole was extracted with AcOEt. The extract was washed with brine, dried over Na 2 SO 4 , and evaporated under reduced pressure to leave a crystalline solid, which was column-chromatographed on SiO 2 with CHCl 3 -hexane (7 : 3, v/v) Compound 25 from 24 A solution of benzyl bromide (64.1 mg, 0.38 mmol) in DMF (1 ml) was added to a suspension of 24 (16.0 mg, 0.067 mmol) and K 2 CO 3 (29.8 mg, 0.22 mmol) in DMF (1 ml), and the mixture was stirred at room temperature for 24 h. After addition of brine, the whole was extracted with AcOEt.…”

“…When the reaction temperature was raised from room temperature to 58°C (entry 5), the yield of 10 was slightly improved to 26%, while the recovery of 1a was still observed. Another interesting finding is that the yield of 9 seems to be almost constant irrespective of the examined reaction conditions (entries [2][3][4][5].…”

“…2) With an aim to carry out their structure-activity relationship studies, several efforts have thus far been reported. 3,4) In 1959, Hofmann and co-workers, 3) and in 1985, Repke and co-workers 4) had undertaken syntheses of psilocin analogs.…”

“…For the structural confirmations of 9 and 10, they were converted to 5-formyl-(11) and 7-formyl-1-tert-butoxycarbonyl-4-tert-butoxycarbonyloxy-N,N-dimethyltryptamine (12) in 78 and 66% yields, respectively, by treating with excess di-tert-butyl dicarbonate [(Boc) 2 …”