Tetrahydro-/i-carboline

Retrosynthetic analysis of hirsutin 108 led to the tetrahydro-/i-carboline (3R)-aldehyde 116, Meldrum s acid 35 and the enol ether 117 via the retrosynthetic intermediates 113-115 (Scheme 5.20) [34]. 

Earlier, a versatile procedure for liquid phase synthesis of l,2,3,4-tetrahydro-/i-carbolines was reported [78], After successful esterification of MeO-PEG-OH with Fmoc-protected tryptophan, one-pot cyclocondensation with a variety of ketones and aldehydes was performed under the action of microwave irradiation (Scheme 16.54). The desired products were released from the soluble support in good yields and high purity. 

Sparteine (Chelidonium majus) (407) lrans-3-Ethylideno-2-pyrrolidone (= corydalac-tame) (Corydalis pallida var. tenuis) (408) Af-Methyltetrahydronorharmane (6-methoxy-2-methyl-1,2,3,4-tetrahydro- i-carboline)... 

These formulae explain the scission products of the two alkaloids and the conversion of evodiamine into rutaecarpine, and were accepted by Asahina. A partial synthesis of rutaecarpine was effected by Asahina, Irie and Ohta, who prepared the o-nitrobenzoyl derivative of 3-)3-amino-ethylindole-2-carboxylic acid, and reduced this to the corresponding amine (partial formula I), which on warming with phosphorus oxychloride in carbon tetrachloride solution furnished rutaecarpine. This synthesis was completed in 1928 by the same authors by the preparation of 3-)S-amino-ethylindole-2-carboxylic acid by the action of alcoholic potassium hydroxide on 2-keto-2 3 4 5-tetrahydro-3-carboline. An equally simple synthesis was effected almost simultaneously by Asahina, Manske and Robinson, who condensed methyl anthranilate with 2-keto-2 3 4 5-tetrahydro-3-carboline (for notation, see p. 492) by the use of phosphorus trichloride (see partial formulae II). Ohta has also synthesised rutaecarpine by heating a mixture of 2-keto-2 3 4 5-tetrahydrocarboline with isatoic anhydride at 195° for 20 minutes. 

The acid-catalyzed conversion of the l,2,3,4-tetrahydro-j8-carboline derivative 337 (R = CHg) into the strychnine-type ring system 338 has been attributed to an equilibrium involving the protonated Schiff s base 339 of tryptamine (i.e., the intermediate in the Pictet-Spengler type synthesis of tetrahydro-j8-carbolines, cf. Section III, A, 1, a), and the a- (337) and the j8-condensation products (340). 

The nitrone 394, prepared from -hy droxytry p tarn i ne 392 and A -BOC- -methyl-D-cysteine 393 <2000JCS(P1)4570>, was treated with trifluoroacetic acid at room temperature to yield the corresponding tetracycle 47 along with the tetrahydro-P-carboline (Scheme 86) <2000J(P1)3487>. 

The (i-carbolinc skeleton with its 9H-pyrido[ 3,4-fr ]indole (29) is frequently encountered in pharmacology due to its activity in the central nervous system at serotonin receptors. It also shows prominent biological properties at the benzodiazepine receptor (BzR) [45]. ZK 93423 (30) remarkably amplifies the agonist activity of such compounds towards BzR. 1,2,3>9-Telrahydro-(>-carbolines are common precursors of (i-carbolines [46]. 1,3.4,9-Tetrahydro-... 

N. Ide, M. Ichikawa, K. Ryu, K. Ogasawara, J. Yoshida, S. Yoshida, T. Sasaoka, S.-I. Sumi, and H. Sumiyoshi, Antioxidants in processed garlic. II. Tetrahydro-b-carboline derivatives identified in aged garlic extract, in G, 2002, 449 150. 

The first-suggested structure of rutaecarpine was based upon an erroneous identification of one of the products of its fission with alkali (2, 3). The fission fragment ultimately proved to be tryptamine (7), and this led to the correct structure (I), since the second fragment had already been recognized as anthranilic acid. An early synthesis was achieved by condensing l-keto-l,2,3,4-tetrahydro-2-carboline with methylanthra-... 

Other examples of tetrahydro-j8-carbolines, (I), prepared by the author are described (3). 

The simplest of the group is the base (13), isolated from Dracontomelum mangiferum and was shown to be in partially racemic form by the synthesis and resolution of the compound. The ( —)-isomer (13) slightly predominates in the natural mixture the absolute configuration was assigned by o.r.d. comparison " with yohimbine and i/ -yohimbine. In fact this is the only simple tetrahydro-jS-carboline alkaloid yet obtained which is not completely racemic. 

The major alkaloid, roxburghine D, has been assigned the structure (96). The U.V. spectrum of this base is a superimposition of the absorptions of two tetrahydro-jS-carbolines and one ) -alkylamino-acrylic ester. The latter is responsible for strong i.r. bands at 1661 and 1613 cm (KBr) and is contained in the... 

The structural state of membranes was studied by EPR-spectroscopy using paramagnetic spin probes [8], Rat and mice blood erythrocytes and mice EAC cells were incubated in the presence of ichfan for 45 min then, probes were inserted. The microviscosity of various membrane sites was measured on an ER 200D-SRC spectrometer (Bruker, Germany). Probe I (2.2.6.6-tetramethyl-4-capryloyl-oxypiperidine-l-oxyl) is localized mainly in the surface lipid bilayer of membrane probe II (5.6-benzo-2.2.6.6-tetramethyl-1.2.3.4-tetrahydro-y-carboline-3-oxyl) permeates into deep-located near-protein sites of the lipid bilayer. From the EPR spectra obtained, using the formula for rapidly rotating probes, the rotation correlation time... 

Figure 1. Dose-response diagram for the effect of ichfan on micro viscosity of the erythrocyte (A), and of the cell of Ehrlich ascitic carcinoma (B). Probe I (light) (2,2,6,6-tetramethyl-4-capryloyl-oxypiperidin-l-oxyl) is localized in the surface layer of the membrane lipid bilayer Probe II (dark) (5,6-benzo-2,2,6,6-tetramethyl-l,2.3,4-tetrahydro-y-carbolin-3-oxyl) in the deep near-protein sites of lipids.

Activation of imines." The electrophilic reaction of imines with organometal-lic reagents such as RMgX, RLi, R2CuLi is promoted by a Lewis acid (BFi OEta). A flexible synthesis of I-substituted l,2,3,4-tetrahydro-)3-carbolines is based on the process. 

Adachi, J., Mizoi, Y., Naito, T., Ogawa, Y., Uetani, Y. and Ninomiya, I. (1991a) Identification of tetrahydro-beta-carboline-3-carboxylic acid in foodstuffs, human urine and human milk. J. Nutr. 121 646-652. 

MethyI-i,2,3,4-TetraHydro-p-carboline (mthc)-I7I-2,176,220 i-methyl-tearahydrocarboline-3-carboxylic acid-194,327... 

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