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The Pictet-Spengler reaction of N-hydroxytryptamine (6) with various aldehydes was examined. Reduction of 3-(2-nitroethyl) indole (5) with aluminum amalgam gave 6, which was not so stable and was readily oxidized to the azoxy compound (10) in solution under an oxygen atmosphere. Reaction of 6 with saturated aldehydes gave the corresponding nitrones (11b, c) without an acid catalyst at room temperature, while the reaction with α, β-unsaturated aldehydes provided nitrones (11d, e, f) in the presence of trifluoroacetic acid. Cyclization of the nitrones with trifluoroacetic acid in methylene chloride gave the 2-hydroxy-1, 2, 3, 4-tetrahydro-β-carbolines (2) in good yields. The cyclization of the saturated nitrones proceeded rapidly, whereas the similar reaction of the unsaturated nitrones was slow. Direct Pictet-Spengler reaction of 6 with aldehydes in methylene chloride in the presence of trifluoroacetic acid gave 2a, b, c in excellent yields. Dehydration of the 2-hydroxy-β-carboline (2b) with trifluoroacetic anhydride in benzene gave the 3, 4-dihydro-β-carboline (15). 6-Bromo-5-methoxy-N-hydroxytryptamine (25) was prepared from 3-bromo-4-methyoxyaniline (17) via the indole (22). The Pictet-Spengler reaction of 25 with isovaleraldehyde gave the 2-hydroxy-tetrahydro-β-carboline (26).

Three marine β-carboline alkaloids, eudistomin H, I, and P (5, 4, and 6), were synthesized by Bischler-Napieralski reaction

Alkylation of 3,4-dihydro-β-carboline has been accomplished with organo-copper and -lithium reagents by activation of BF3·OEt2 or trimethylsilyl trifluoromethanesulphonate.

Bicyclic 5-hydroxy-2-pyrrolidinones (2a - f) were synthesized with high enantioselectivity by the reduction of meso-cyclic-1,2-dicarboximides (1a - f) with lithium aluminum hydride (LiAlH 4 )-methanol (MeOH)-1,1'-bi-2-naphthol complex (BINAL-H). Treatment of 2a - f with triethylsilane (Et 3 SiH) and trifluoroacetic acid(CF 3 CO 2 H) gave optically active 2-pyrrolidinones (3a - f) in quantitative yields. For the absolute configuration correlation, 2a - d were converted into known lactones (4a - d)

Efficient methods for the Michael addition reactions of N-arylsulfonyl-3-phenylthiopiperidones (1) with both the protected amidoacrylates (4, 9) and the simple acrylates (12) have been developed. These reactions offer an efficient route to the 3-alkyl-substituted dihydropyridinones (3, 11), the dienophiles employed in the natural product synthesis

The first total synthesis of symbioramide 1 has been accomplished by the coupling of D-erythro-dihydro-sphingosine with an unusual, chiral α-hydroxy-βγ-unsaturated fatty acid prepared from L-ascorbic acid, and simultaneously established the complete stereostructure of 1 to be (2S, 2′R, 3R, 3′E)-N-(2′-hydroxyoctadec-3′-enoyl)dihydrosphingosine.

The Pictet-Spengler reaction of the imine (9) with chloro (-)-diisopinocamphenylborane yielded optically spiroindolines (14) and (15), providing a new evidence for the presence of a spiroindolenium intermediate

(-)Eudistomin F was synthesized in optically pure form from 6-bromo-5-methoxy-N b -hydroxytryptamine and D-cysteinal

Various hydroisoquinolines have been synthesized via the Diels-Alder reactions of 5,6-dihydro-2-pyridinones with Danishefsky diene

Indole reacted with (propargyl alcohol)Co 2 (CO) 6 complex 1 to give 3-(1,1-dimethylpropargyl)indole 3, whereas N'-methoxycarbonyltryptamine 7 gave the corresponding N-substituted derivative 11. The reaction of 7 with (propargyl acetate)Co 2 (CO) 6 complex 23 provided 3a-(1,1-dimethylpropargyl)hexahydropyrroloindole cobalt complex 9. Oxidative demetalation of 3, 11, and 9 with Fe(NO 3 ) 3 gave 5,13, and 27, respectively. Hydrogenation of 5 afforded the corresponding 3-(1,1-dimethylallyl)indole 6

A new sphingosine derivative (1) from Anemonia sulcata has been synthesized and the L-erythro configuration determined.

Pictet-Spengler reaction of L-tryptophan methyl ester (9) and 6-methoxy-L-tryptophan methyl ester (40) with isovaleraldehyde (10) in methylene chloride in the presence of trifluoroacetic acid gave the cis-tetrahydro-β-carboline (11, 41) as the major isomer. The condensation of 11 and 41 with N-benzyloxycarbonyl-L-proline followed by deprotection gave the cis-cis-pentacycles (27, 44) which contain the parent ring system of fumitremorgins. The trans-cis(28), the cis-trans (29, 30) and the trans-trans (31) pentacycles were similarly prepared. Isopentylation of 27 and 44 gave the Na-isopentyl derivatives (52, 53) accompanied with epimerization at the 12-position. Oxidation of 52 and 53 with dichlorodicyano-p-benzoquinone (DDQ) gave the 12, 13-dehydro derivatives (54, 55) which provided demethoxy-13-epi-tetrahydrofumitremorgin B (57) and 17-bromo-13-epi-tetrahydro-fumitremorgin B (58) by N-bromosuccinimide (NBS)-oxidation in aqueous dimethoxyethane. Debromination of 58 gave 13-epi-tetrahydrofumitremorgin B (59).

Synthesis of four diastereomeric ceramides including the aglycone of cerebroside B 1b ( 1b ) was described. The crucial step in the synthesis of cerebroside B 1b consists in a regio- and stereoselective formation of the erythro-sphingosine moiety by the reaction of dienal 4 with 2-nitroethanol followed by resolution with optically active α-hydroxypalmitic acids.

The Pictet-Spengle P-S reaction of Nb-hydroxytryptamines 5 and cysteinals 6 in the presence of trifluoroacetic acid(TFA) at room, temperature gave the tetracyclic compounds 7 α as well as the corresponding Nb-hydroxy-β-carbolines 8. The optically active nitrones 9, isolated from the similar reaction of 5 and optically active 6, gave optically active 7 α and 8.

Selective Na-alkylation, 5-chlorination, 5-bromination, and 5-nitration of tryptophan derivatives were achieved. The alkylation of the cyclic tautomer 2 of Nb-methoxycarbonyl-DL-tryptophan methyl ester (1) with alkyl halides in acetone-K2CO3 gave the Na-alkyl derivatives (3a and 4) in excellent yields. The chlorination of the cyclic tautomer 3b with NCS-AcOH gave the 5-chloro derivative (5b) in 89% yield, and this was readily converted to the 5-chlorotryptophan derivatives (7a, 7b, 9). The similar chlorination of 12 gave the 5-chloro derivatives (13a, 15a) and the 3a-chloropyrroloindole derivative (17). On the other hand the bromination of 12 with NBS-AcOH gave the 5-bromo derivative (13b) in good yield, and this was readily converted to 15d and further to 15c. The nitration of 3b and 12 with fuming nitric acid also gave the 5-nitro derivatives (5c, 7c, 13c, 15e) in excellent yields.

Optically active pentacycles ( 13–18 ) were synthesized from L- and D-tryptophans, two of which ( 13 and 15 ) were alkylated and dehydrogenated to 21 and 22 , respectively.

The 5-hydroxytryptophan derivative 12 was prepared in 60% yield from the tryptophan derivative 8 by selective oxidation of the cyclic tautomer 9 with Fremy's salt or Pb (OAc)4-CF3COOH to the p-quinoneimine 10, followed by reduction and ring-opening. By analogous oxidation, serotonin was prepared from tryptamine. On the other hand, the oxidation of the Na-acetyl-cyclic tautomers (16 and 22) with Pb (OAc)4-CF3COOH followed by methylation gave the 5-and 6-methoxy derivatives (17, 18, 23, and 24) in 20-40% yields. These compounds were readily converted to the 5-and 6-methoxytryptophan derivatives (20, 21) by acid treatment. These methods are the first practical hydroxylation procedures to be reported for tryptophans.

Reaction of 3-tert-butylindole (1a) with NBS in acetic acid gave 3-tert-butyloxindole (2a) and 6-bromo-3-tert-butylindole (3a) instead of 2-bromo derivative (5a). Reactions of 1-acetyl-(1b) and 1-tert-butyl-(1c) derivatives under similar conditions gave 3-bromooxindole (6b) and the brominated indole (7) respectively. On the other hand reaction of 1a with NBS in boiling carbon tetrachloride in the presence of benzoyl peroxide gave unstable 5a as a main product. Reaction of 1b under similar condition did not proceed, but 1c gave 7 as a main product.

Three marine β-carboline alkaloids, eudistomin H, I, and P (5, 4, and 6), were synthesized by Bischler-Napieralski reaction

Desulfurization of epidithio-2,5-piperazinediones (6 and 7) by triphenylphosphine in THF gave dimeric compounds (8 and 15). In the presence of water or phenol the desulfurization gave 3-hydroxy (9) or 3-phenoxy-2,5-piperazinedione (10). Reaction of 6c with triphenylphosphine in ethyl vinyl ether yielded 2,5-diazabicyclo[2.2.2]octane-3,6-dione (11), indicating the presence of 1,4-dipole (B) as an intermediate of the desulfurization. Similar cycloaddition products (13 and 14) were obtained by the desulfurization of 6c in the presence of benzofuran, indole or skatole. Desulfurization of open chain disulfides (16, 21, 23 and 25) by triphenylphosphine gave reduced products (17, 22 and 26) and an isoxazole (18), but CC bond formation was not observed.

Le compose du titre est prepare a partir d'[indolyl-3]-2' ethylamide de l'acide R-3 thiazolidinecarbothioique-4 acide (R=methoxycarbonyl) par reaction de Bischler Napieralski et reduction suivies de transposition chimique de la [R-3 thiazolidinyl-4]-1 tetrahydro-1,2,3,4 β-carboline obtenue

The reaction of tryptamine with δ-valerolactone in tetralin gave δ-hydroxyamide (3) as the main product and the lactam (4) as the minor product. However, the reaction of 5, 6-dihydro-2-pyrone with tryptamine or aniline afforded a mixture of the corresponding αβ- and βγ-unsaturated lactams, whereas, 2-pyrone did not react with either tryptamine or aniline to give the corresponding pyridone. Cyclization of 3 or 4 by Bischler-Napieralski reaction and followed NaBH4 reduction provided a convement synthesis of 1, 2, 3, 4, 6, 7, 12, 12b-octahydroindolo [2, 3-α] quinolizine (23).

Imidazo [1, 2-a] indole-spirolactone 13, the principal ring system of tryptoquivalines, was successfully synthesized by a new method via oxidative double cyclization of 1-(N-alkoxy-carbonylalanyl)-3-indolepropionic acids (5) with N-bromosuccinimide, which were synthesized by acylation of benzyl 3-indolepropionate (10) with N-alkoxycarbonyl alanine p-nitrophenyl ester (12). The use of KF, 18-crown-6 and (iso-Pr)2NEt in acetonitrile lead to high yields of benzyl 1-(N-methoxycarbonyl-α-methylalanyl)-3-indolepropionates (4). The removal of the protecting group of 13c provided 2. The mechanisms of these reactions are discussed.

First total synthesis of ditryptophenaline 1 is described and the absolute configuration was determined.

First total synthesis of optically active cerebroside B1b (1b) is described. The absolute configuration of 1b was determined to be (2 S ,3 R ,4 E ,8 Z ,2′ R )-1- O -(β-D-glucopyranosyl)- N -(2′-hydroxyhexadecanoyl)-4,8-sphingadienine.

The isolation, structure determination, and reactivity of the tricyclic labile hydroperoxides 10 and 2 obtained by dye-sensitized photooxygenation of L-, D-, and DL-tryptophan and Nb-methoxycarbonyltryptophan ester are reported. The tricyclic hydroperoxide 10, under appropriate conditions, was easily convertible to formylkynurenine. Plausible mechanisms for these transformations are discussed.

Total synthesis of the title compounds is described. The key intermediate, dehydro-pentacyclic 13, is prepared in a sequence involving Pictet-Spengler reaction and DDQ oxidation. The key step in the synthesis was the dihydroxylation of 13 to afford the cis -diol 54, which was performed by direct oxidation with osmium tetroxide, whereas treatment of 13 with N-bromo-succinimide provided the trans -diol 41. Subsequent selective prenylation of 41 and 54 gave 13-epi-fumitremorgin B (45) and fumitremorgin B (1), respectively. 13-Epi-compound 45 is also converted into fumitremorgin B (1) by oxidation followed by reduction.

Halogenation of skatole (1a) and 1-acetyl (1b), 1-benzenesulfonyl (1c), and 1-tosylskatole (1d) with N-bromosuccinimide (NBS) N-chlorosuccinimide (NCS), N-iodosuccinimide (NIS) in acetic acid or carbon tetrachloride has been studied. Bromination of 1a with NBS in carbon tetrachloride in the presence of benzoyl peroxide yielded 2-bromoskatole (2a) in 85% yield. reaction of 1b with NBS (NCS) in acetic acid or in carbon tetrachloride yielded 1-acetyl-2-(1-acetyl-3-indolylmethyl)-3-methylindole (7b) and 2-halo derivative (2b). The reaction of 2b (X=Br) with skatole or 3-methyloxindole gave 1-acetylskatole (1b). Bromination of 1c (1d) with NBS in carbon tetrachloride yielded 3-bromomethyl derivative (6c or 6d). On the other hand the reaction of (1c or 1d) with NBS in acetic acid gave 2-bromo derivative (2c or 2d) and the 3-bromo-oxindole (5c or 5d). Mechanism of the formation of 7b and other products has been discussed.

Oxytryptophans 3 , which are readily obtained by dye-sensitized photooxygenation of tryptophan followed by acid treatment, undergo a facile N,N′-transacylation to give the 3-(2-aminophenyl)-2-pyrrolidones 4 in the absence of oxygen, whereas in the presence of oxygen 3a was oxidized to kynurenine.

Prenylation of Nb-acyltryptamines provided 3a,8-diprenylpyrroloindoles 6 which were rearranged to 1,2-diprenyltryptamines 8 . Dye-sensitized photooxygenation of the tetrahydro derivative 9 gave 3a-hydroxide 11 which was converted to the β-carboline 15 by CF 3 CO 2 H, showing a new method of β-carboline synthesis and also suggesting a new possible biosynthetic pathway of Fumitremorgin B.

Two stereoisomeric cyclic tautomers ( 5 and 6 of cyclo-L-tryptophanyl-L-proline whose stereochemistry was established by x-ray analysis, gave 5- and 6-hydroxytryptophanyl derivatives ( 10 ), 11 , and 19 ) on the hydroxylation with lead tetraacetate in trifluoroacetic acid.

Dye-sensitized photo-oxygenation of L-tryptophan (1) has been studied at various pH and in various buffers. Disappearance of 1 in both acetate and phosphate buffers was rapid at higher pH. The tricyclic hydroperoxide (8) was the sole product in the oxidation of 1 over the range pH 3.6–7.1 in acetate and phosphate buffers. However, the oxidation of 1 in alkaline phosphate and borate buffers (pH 7.7–8.4) gave 5-hydroxyformylkynurenine (10) as the major product. The intermediate, 3a,5-dihydroxypyrroloindole (16), which may be formed from the tricyclic hydroperoxide (8) via the quinoneimine (15), was obtained in good yield by the immediate reduction of the reaction mixture with NaBH4. Molecular oxygen (ground state) oxidation of 16 in the alkaline media provided 10. The similar oxidation and reduction of tryptamine (17a) gave 3a,5-dihydroxypyrroloindole (18b) which was not further oxidized to 5-hydroxyformylkynureamine. On the other hand, dye-sensitized photo-oxygenation of 1 in Na2CO3-AcOH (pH 7) gave formylkynurenine (3) as the major product.

We report the first total synthesis of (+)-tryptoquivaline 1a and of a key precursor, 2,3-dialkylquinazolinone 13b.