First total synthesis of β-carboline alkaloid trigonostemine G and its derivatives

Article abstract of DOI:10.1080/14786419.2019.1613401

The β-carboline core is the base structure of several biologically active natural and unnatural compounds. Herein, we report the first total synthesis of trigonostemine G, which is a newly isolated natural β-carboline alkaloid from the twigs of Trigonostemon filipes. Synthesis of two structurally close derivatives of trigonostemine G is also reported. Key step of the syntheses involves a nucleophilic addition of 5-{[tert-butyl(dimethyl) silyl]oxy}-1H-indole to 1-formyl-β-carboline building blocks.

Full text of DOI:10.1080/14786419.2019.1613401

Natural Product Research
Formerly Natural Product Letters
ISSN: 1478-6419 (Print) 1478-6427 (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20
First total synthesis of β-carboline alkaloid
trigonostemine G and its derivatives
Tímea Szabó, András Dancsó, Balázs Volk & Mátyás Milen
To cite this article: Tímea Szabó, András Dancsó, Balázs Volk & Mátyás Milen (2019): First total
synthesis of β-carboline alkaloid trigonostemine G and its derivatives, Natural Product Research,
DOI: 10.1080/14786419.2019.1613401
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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2019.1613401
First total synthesis of b-carboline alkaloid
trigonostemine G and its derivatives
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ꢀ ꢀ
Tımea Szabo, Andras Dancso, Balazs Volk and Matyas Milen
Egis Pharmaceuticals Plc., Directorate of Drug Substance Development, Budapest, Hungary
ABSTRACT
ARTICLE HISTORY
Received 11 March 2019
Accepted 24 April 2019
The b-carboline core is the base structure of several biologically
active natural and unnatural compounds. Herein, we report the
first total synthesis of trigonostemine G, which is a newly isolated
natural b-carboline alkaloid from the twigs of Trigonostemon
filipes. Synthesis of two structurally close derivatives of
trigonostemine G is also reported. Key step of the syntheses
KEYWORDS
Total synthesis;
b-carbolines; indoles;
trigonostemine G;
natural products
involves
a
nucleophilic addition of 5-f[tert-butyl(dimethyl)
silyl]oxyg-1H-indole to 1-formyl-b-carboline building blocks.
1. Introduction
b-Carboline alkaloids, major representatives of natural products, are widespread in the
plant kingdom, and among mammals, insects and marine organisms (Love 1996;
McNulty and Still 2000; Rosillo et al. 2008). Both natural and synthetic b-carboline
derivatives exhibit a broad spectrum of biological and pharmacological activities (Cao
ꢁ
et al. 2007; Patel et al. 2012; Laine et al. 2014; Laviīa et al. 2016). Very recently, trigo-
nostemine G (1a, Figure 1) has been isolated from the twigs of Trigonostemon filipes
and it showed weak cytotoxicity against K562 human cancer cell line (Wang et al.
2018). Trigonostemon filipes belongs to the plants of the Trigonostemon genus
(Euphorbiaceae family) and so far eight indole alkaloids have been isolated from it (Li
et al. 2012; Xu and Yue 2014; Wang et al. 2018). In a very recent publication, we have
described an efficient preparation of the versatile synthetic building blocks, 1-formyl-
9H-b-carboline derivatives (2a–c), using easily available starting materials and reagents
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(Szabo et al. 2019). These building blocks (2a–c) have been successfully applied in the
ꢀ ꢀ
CONTACT Matyas Milen
milen.matyas@egis.hu
Egis Pharmaceuticals Plc., Directorate of Drug Substance
Development, 1475 Budapest, Budapest, Hungary P.O.B. 100.
Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1613401.
ß 2019 Informa UK Limited, trading as Taylor & Francis Group

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T. SZABO ET AL.
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Figure 1. Structure of natural and synthetic b-carbolines.
Scheme 1. Direct synthetic approach for the preparation of the hydroxy intermediate of trigonoste-
mine G (8).
first total synthesis of trigonostemine A (3) and trigonostemine B (4), and in a new
ꢀ
total synthesis of pityriacitrin (5) and hyrtiosulawesine (6) (Szabo et al. 2019). By con-
tinuing and extending of the research in the field of b-carboline chemistry (Milen
ꢀ
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et al. 2016; Abranyi-Balogh et al. 2018) we herein report the first total synthesis of the
lately discovered trigonostemine G (1a) and two closely related compounds (1b,c).
2. Results and discussion
First, the reaction of 1-formyl-7-methoxy-b-carboline (2a) and 5-hydroxyindole (7) were investi-
gated to synthesise hydroxy derivative 8, a potential key intermediate of trigonostemine G
(1a, Scheme 1). This reaction was carried out in the presence of NaOH at room temperature,
ꢀ
similarly to the earlier preparation of analogous secondary alcohols (Szabo et al. 2019).
However, the desired nucleophilic addition at the indole C(3) position did not take place and
only the starting materials could be detected in the reaction mixture after 48 hours.
The earlier synthetic pathway applying unprotected indole 7 proved to be
unsuccessful therefore we tried to use a 5-hydroxyindole derivative bearing a t-butyldi-
methylsilyl (TBS) protecting group (Ito et al. 2011). Aldehydes 2a–c were treated with
5-f[tert-butyl(dimethyl)silyl]oxyg-1H-indole (9) under slightly alkaline conditions (to
increase the nucleophilicity of 9) to give hydroxy compounds 10a–c in moderate
yields (37–45%, Scheme 2). Reaction in much more alkaline medium or the addition of
excess amount of indole derivative was not considered as beneficial because of the
formation of disubstituted two indole containing side products (Deb and Bhuyan
2006; Deb et al. 2017). The next step of the synthesis was the oxidation of the second-
ary alcohols (10a–c) using activated MnO2 in boiling 1,4-dioxane. Ketone intermediates
11a–c were obtained in excellent yields (98–99%). The protecting group removal was
investigated with two reagents. The reaction with tetrabutylammonium fluoride (TBAF)
also provided the deprotected products, however they were contaminated by TBAF

NATURAL PRODUCT RESEARCH
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Scheme 2. Total synthesis of trigonostemine G (1a) and its isomeric (1b) and demethoxy (1c)
derivatives.
residues and the purification proved to be odd. Finally, the tert-butyl(dimethyl)silyl
(TBS) protecting group was easily removed from the compounds 11a–c with CsF in
acetonitrile at room temperature (Marino et al. 2011). By this method trigonostemine
G (1a), its isomer derivative (5-hydroxy-1H-indol-3-yl)(6-methoxy-9H-b-carbolin-1-yl)me-
thanone (1b), and demethoxy trigonostemine G (1c) were prepared from the appropri-
ate 1-formyl-9H-b-carbolines (2a–c) in 39, 39, and 34% overall yield, respectively.
The structures of the synthesised products were characterised by IR, 1H and 13C
NMR spectroscopy, as well as high-resolution mass spectrometry. The NMR data of the
prepared trigonostemine G (1a) are identical to the natural product described by
Wang and co-workers (Table S1, Wang et al. 2018).
3. Experimental
3.1. General experimental procedures
€
€
All melting points were determined on a Buchi–Boetius microapparatus and are uncor-
rected. IR spectra were obtained on a Bruker Alpha FT-IR spectrometer in KBr pellets
1
or film. H NMR and 13C NMR spectra were recorded in DMSO-d6 or CDCl3 solution in

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T. SZABO ET AL.
4
5 mm tubes at room temperature, on a Bruker Avance III HD 600 (600 and 150 MHz for
1H and 13C NMR spectra, respectively) or a Bruker Avance III 400 (400 and 100 MHz for
1H and 13C NMR spectra, respectively) spectrometer with the deuterium signal of the
solvent as the lock and TMS as the internal standard. Chemical shifts (d) and coupling
constants (J) are given in ppm and in Hz, respectively. The following abbreviations are
used to designate multiplicities: s ¼ singlet, d ¼ doublet, t ¼ triplet, m ¼ multiplet,
br ¼ broad. Mass spectra were recorded on a Bruker O-TOF MAXIS Impact mass spec-
trometer coupled to a Dionex Ultimate 3000 RS HPLC system with a diode array
detector. Reactions were monitored by thin-layer chromatography (TLC) carried out on
silica gel plates (60 F254) using UV light as visualizing agent. Purifications by flash col-
umn chromatography were carried out using Merck 107736 silica gel 60 H with a
hexane–CH2Cl2 or CH2Cl2–MeOH solvent system. All reagents were purchased from
commercial sources and used without further purification. Analytical samples of new
compounds were obtained by recrystallization from the solvents or solvent mixtures
given below in parentheses.
3.2. Synthesis of 5-f[tert-butyl(dimethyl)silyl]-1H-indole (9)
5-Hydroxyindole (7, 18.78 mmol) and tert-butyldimethylsilyl chloride (19.72 mmol) were
dissolved in DMF (25 mL). Then imidazole (40 mmol) was gently added to the reaction
mixture and the black solution was stirred at room temperature for 24 hours. After the
reaction was complete, Et2O (60 mL) was added and the mixture was stirred. The reac-
tion mixture was washed with 1 M HCl solution and water, dried over Na2SO4, filtrated
and evaporated under reduced pressure. The crude residue was purified by flash col-
umn chromatography (hexane–EtOAc) to afford product 9.
3.3. General procedure for the preparation of (5-f[tert-butyl(dimethyl)silyl]oxyg-
1H-indole-3-yl)(9H-b-carbolin-1-yl)methanols (10a–c)
The appropriate formyl-b-carbolines (2a–c, 2.55 mmol) and protected indole (9,
2.55 mmol) were dissolved in the mixture of CH2Cl2 (37 mL) and EtOH (27 mL) and an
aqueous solution of NaOH (1.27 mmol in 0.2 mL water) was added to the reaction. The
reaction mixture was stirred at room temperature for 48 h. The reaction mixture was
dried over Na2SO4 and evaporated to silica gel. Products 10a–c were obtained by flash
column chromatography using CH2Cl2–MeOH gradient.
3.3.1. (5-f[Tert-butyl(dimethyl)silyl]oxyg-1H-indole-3-yl)(7-methoxy-9H-b-carbolin-1-
yl)methanol (10a)
Yield: 0.543 g (45%). C27H31N3O3Si, brown crystals. Mp 127–130 ꢀC (hexane–EtOAc); IR
(KBr): ꢀmax 3451, 2928, 1632, 1474, 1265, 1215, 803 cm–1; 1H NMR (DMSO-d6,
400 MHz): d 10.98 (s, 1H), 10.56 (d, J ¼ 2.0 Hz, 1H), 8.17 (d, J ¼ 5.2 Hz, 1H), 8.02 (d,
J ¼ 8.8 Hz, 1H), 7.84 (d, J ¼ 5.2 Hz, 1H), 7.39 (d, J ¼ 2.4 Hz, 1H), 7.19 (d, J ¼ 2.0 Hz, 1H),
7.12 (d, J ¼ 8.4 Hz, 1H), 7.00 (d, J ¼ 2.4 Hz, 1H), 6.59 (dd, J1 ¼ 2.4, Hz, J2 ¼ 8.8 Hz,
1H), 6.27 (d, J ¼ 3.6 Hz, 1H), 6.16 (d, J ¼ 4.0 Hz, 1H), 3.84 (s, 3H), 0.87 (s, 9H), 0.02
(s, 3H),

NATURAL PRODUCT RESEARCH
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ꢁ0.01 (s, 3H) ppm; 13C NMR (DMSO-d6, 100 MHz): d 160.2, 147.7, 147.0, 142.3, 136.9,
132.5, 132.2, 128.9, 126.3, 123.9, 122.3, 117.2, 115.1, 114.4, 112.9, 111.7, 109.12, 109.10,
95.3, 71.1, 55.4, 25.8, 18.1, –4.51, –4.46 ppm; HRMS calcd. for C27H32N3O3Si [M þ H]þ
474.2213; found 474.2208.
3.3.2. (5-f[Tert-butyl(dimethyl)silyl]oxyg-1H-indole-3-yl)(6-methoxy-9H-b-carbolin-1-
yl)methanol (10b)
Yield: 0.531 g (44%). C27H31N3O3Si, pale brown crystals. Mp 118–120 ꢀC (CH3CN); IR
1
(KBr): ꢀmax 3398, 2923, 1600, 1473, 1208, 1147, 719 cm–1; H NMR (DMSO-d6, 600 MHz):
d 10.97 (s, 1H), 10.75 (d, J ¼ 2.3 Hz, 1H), 8.18 (d, J ¼ 5.3 Hz, 1H), 8.95 (d, J ¼ 5.3 Hz, 1H),
7.71 (d, J ¼ 2.5 Hz, 1H), 7.61 (s, 1H), 7.60 (d, J ¼ 0.2 Hz, 1H), 7.40 (d, J ¼ 2.5 Hz, 1H),
7.11–7.17 (m, 2H), 7.00 (d, J ¼ 2.4 Hz, 1H), 6.53 (dd, J1 ¼ 2.4 Hz, J2 ¼ 8.5 Hz, 1H), 6.30
(dd, J1 ¼ 0.5 Hz, J2 ¼ 4.0 Hz, 1H), 6.18 (d, J ¼ 4.0 Hz, 1H), 3.84 (s, 3H), 0.88 (s, 9H), 0.02
(s, 3H), 0.01 (s, 3H) ppm; 13C NMR (DMSO-d6, 150 MHz): d 153.3, 147.79, 147.77, 136.0,
135.6, 132.9, 132.2, 128.4, 126.3, 123.9, 120.9, 118.0, 117.1, 115.1, 113.7, 113.5, 111.8,
109.1, 103.2, 71.1, 55.8, 25.9, 18.1, –4.41, –4.41 ppm; HRMS calcd. for C27H32N3O3Si
[M þ H]þ 474.2213; found 474.2208.
3.3.3. (5-f[Tert-butyl(dimethyl)silyl]oxyg-1H-indole-3-yl)(9H-b-carbolin-1-yl)metha-
nol (10c)
Yield: 0.423 g (37%). C26H29N3O2Si, brown crystals. Mp 136–138 ꢀC (Et2O); IR (KBr): ꢀmax
1
3322, 2817, 1655, 1486, 1387, 1245, 802 cm–1; H NMR (DMSO-d6, 400 MHz): d 11.15 (br
s, 1H), 10.75 (d, J ¼ 2.0 Hz, 1H), 8.23 (d, J ¼ 5.2 Hz, 1H), 8.17 (d, J ¼ 7.8 Hz, 1H), 7.97 (d,
J ¼ 5.2 Hz, 1H), 7.70 (d, J ¼ 8.2 Hz, 1H), 7.51–7.47 (m, 1H), 7.40 (d, J ¼ 2.4 Hz, 1H),
7.21–7.13 (m, 1H), 7.04 (d, J ¼ 8.7 Hz, 1H), 6.75 (d, J ¼ 2.32 Hz, 1H), 6.20 (br s, 1H), 0.87
(s, 9H), 0.01 (s, 3H), –0.01 (s, 3H) ppm; 13C NMR (DMSO-d6, 100 MHz): d 147.8, 147.7,
140.7, 136.6, 132.4, 132.2, 128.6, 127.9, 126.3, 123.9, 121.5, 120.7, 119.2, 117.1, 115.1,
113.6, 112.6, 111.8, 109.1, 71.1, 25.9, 18.1, –4.49, –4.45 ppm; HRMS calcd. for
C26H30N3O2Si [M þ H]þ 444.2107; found 444.2101.
3.4. General procedure for the preparation of (5-f[tert-butyl(dimethyl)silyl]oxyg-
1H-indole-3-yl)(9H-b-carbolin-1-yl)methanones (11a–c)
Secondary alcohols 10a–c (0.45 mmol) were dissolved in 1,4-dioxane and activated
MnO2 (4.51 mmol, 0.392 g) was added. The mixture was stirred at reflux temperature
for 30 minutes. After the reaction was complete, the inorganic solid residue was
removed by filtration. The organic solution was evaporated to afford the appropri-
ate ketones.
3.4.1. (5-f[Tert-butyl(dimethyl)silyl]oxyg-1H-indole-3-yl)(7-methoxy-9H-b-carbolin-1-
yl)methanone (11a)
Yield: 0.209 g (98%). C27H29N3O3Si, yellow semisolid; IR (film): ꢀmax 3344, 2999, 1667,
1496, 1247, 1138, 923 cm–1; 1H NMR (CDCl3, 600 MHz): d 10.70 (br s, 1H), 9.37 (d,
J ¼ 3.1 Hz, 1H), 8.82 (br s, 1H), 8.50 (d, J ¼ 4.9 Hz, 1H), 8.17 (d, J ¼ 2.4 Hz, 1H), 8.01 (dd,
J1 ¼ 2.8 Hz, J2 ¼ 11.0 Hz, 2H), 7.30 (d, J ¼ 8.6 Hz, 1H), 7.04 (d, J ¼ 2.2 Hz, 1H), 6.92 (dd,

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T. SZABO ET AL.
6
J1 ¼ 2.2 Hz, J2 ¼ 8.6 Hz, 1H), 6.88 (dd, J1 ¼ 2.4 Hz, J2 ¼ 8.6 Hz, 1H), 3.93 (s, 3H), 1.05 (s,
9H), 0.28 (s, 6H) ppm; 13C NMR (CDCl3, 150 MHz): d 188.8, 161.5, 151.9, 142.7, 137.8,
137.7, 137.3, 136.7, 131.5, 130.9, 128.5, 122.6, 117.4, 116.8, 115.6, 114.5, 112.6, 111.6,
110.0, 94.9, 55.6, 25.8, 18.3, –4.4 ppm; HRMS calcd. for C27H30N3O3Si [M þ H]þ
472.2056; found 472.2050.
3.4.2. (5-f[Tert-butyl(dimethyl)silyl]oxyg-1H-indole-3-yl)(6-methoxy-9H-b-carbolin-1-
yl)methanone (11b)
Yield: 0.211 g (99%). C27H29N3O3Si, yellow semisolid; IR (KBr): ꢀmax 3379, 2929, 1612,
1492, 1285, 1111, 971 cm–1; 1H NMR (CDCl3, 600 MHz): d 10.61 (br s, 1H), 9.31 (d,
J ¼ 3.1 Hz, 1H), 9.31 (br s, 1H), 8.49 (d, J ¼ 4.9 Hz, 1H), 8.17 (d, J ¼ 2.4 Hz, 1H), 8.06 (d,
J ¼ 5.0 Hz, 1H), 7.58 (d, J ¼ 8.8 Hz, 1H), 7.22–7.29 (m, 2H), 6.87 (dd, J1 ¼ 2.4 Hz, J2 ¼
8.6 Hz, 1H), 3.94 (s, 3H), 1.05 (s, 9H), 0.28 (s, 6H) ppm; 13C NMR (CDCl3, 150 MHz): d
188.7, 154.3, 151.9, 138.4, 137.2, 137.0, 136.8, 135.9, 131.1, 130.8, 128.4, 121.1, 118.7,
117.6, 117.4, 115.5, 112.7, 112.6, 111.5, 103.7, 56.0, 25.8, 18.3, –4.4 ppm; HRMS calcd.
for C27H30N3O3Si [M þ H]þ 472.2056; found 472.2051.
3.4.3.
yl)methanone (11c)
(5-f[Tert-butyl(dimethyl)silyl]oxyg-1H-indole-3-yl)(9H-b-carbolin-1-
Yield: 0.195 g (98%). C26H27N3O2Si, yellow semisolid; IR (KBr): ꢀmax 3442, 3224, 2928,
1595, 1464, 1132, 931 cm–1; 1H NMR (CDCl3, 600 MHz): d 10.75 (br s, 1H), 9.35 (d,
J ¼ 3.1 Hz, 1H), 8.71 (br s, 1H), 8.18 (d, J ¼ 4.9 Hz, 1H), 8.17 (d, J ¼ 2.4 Hz, 1H), 8.14 (dd,
J1 ¼ 0.8 Hz, J2 ¼ 7.8 Hz, 1H), 8.11 (dd, J1 ¼ 0.5 Hz, J2 ¼ 4.9 Hz, 1H), 7.62–7.58 (m, 2H),
7.33–7.30 (m, 1H), 7.29 (dd, J1 ¼ 0.5 Hz, J2 ¼ 8.6, 1H), 6.88 (dd, J1 ¼ 2.4 Hz, J2 ¼ 8.6 Hz,
1H), 1.05 (s, 9H), 0.28 (s, 6H) ppm; 13C NMR (CDCl3, 150 MHz): d 188.7, 151.9, 141.0,
138.3, 137.4, 137.3, 136.5, 131.3, 130.8, 129.0, 128.4, 121.7, 120.8, 120.3, 117.7, 117.5,
115.6, 112.9, 111.9 111.5, 25.8, 18.3, ꢁ4.3 ppm; HRMS calcd. for C26H28N3O2Si [M þ H]þ
442.1951; found 442.1946.
3.5. General procedure for the preparation of 9H-b-carbolin-1-yl(5-hydroxy-1H-
indol-3-yl)methanones (1a–c)
The appropriate ketone (13a–c, 0.34 mmol) was dissolved in CH3CN (15 mL), the mix-
ture was cooled to 0 ꢀC and CsF (0.41 mmol, 1.2 eq) was added in one portion. The
mixture was allowed to warm to room temperature and it was stirred overnight. The
reaction mixture was quenched with an aqueous solution of concentrated NaHCO3
(15 mL) and the organic solvents were evaporated. Water (15 mL) was added to the
residue and the aqueous mixture was extracted with dichloromethane (3 ꢂ 10 mL) The
combined organic layers were dried (Na2SO4), filtered, and evaporated. The product
was purified by recrystallization from CH3CN.
3.5.1. (5-Hydroxy-1H-indol-3-yl)(7-methoxy-9H-b-carbolin-1-yl)methanone (1a)
Yield: 0.107 g (88%). C21H15N3O3, yellow crystals. Mp >300 ꢀC (CH3CN, decomp.); IR
(KBr): ꢀmax 3339, 1601, 1473, 1250, 1142, 916, 757 cm–1; HRMS calcd. for C21H16N3O3
[M þ H]þ 358.1192; found 358.1186.

NATURAL PRODUCT RESEARCH
7
3.5.2. (5-Hydroxy-1H-indol-3-yl)(6-methoxy-9H-b-carbolin-1-yl)methanone (1b)
Yield: 0.108 g (89%). C21H15N3O3, yellow crystals. Mp >300 ꢀC (CH3CN, decomp.); IR
1
(KBr): ꢀmax 3387, 3329, 1494, 1470, 1205, 1130, 800 cm–1; H NMR (DMSO-d6, 600 MHz):
d 11.80 (br s, 2H), 9.13 (br s, 2H), 8.51 (d, J ¼ 4.9 Hz, 1H), 8.37 (d, J ¼ 4.9 Hz, 1H), 7.95
(d, J ¼ 2.2 Hz, 1H), 7.87 (d, J ¼ 2.4 Hz, 1H), 7.75 (d, J ¼ 8.9 Hz, 1H), 7.36 (d, J ¼ 8.5 Hz,
1H), 7.24 (dd, J1 ¼ 2.6 Hz, J2 ¼ 8.9 Hz, 1H), 6.78 (dd, J1 ¼ 2.4 Hz, J2 ¼ 8.6 Hz, 1H), 3.89
(s, 3H) ppm; 13C NMR (DMSO-d6, 150 MHz): d 187.3, 153.9, 153.6, 139.0, 138.0, 136.6,
136.5, 135.6, 130.7, 130.3 128.6, 120.6, 118.8, 118.0, 114.1, 114.0, 112.8 (2 C), 106.6,
103.7, 55.8 ppm; HRMS calcd. for C21H16N3O3 [M þ H]þ 358.1192; found 358.1186.
3.5.3. 9H-b-Carbolin-1-yl(5-hydroxy-1H-indol-3-yl)methanone (1c)
Yield: 0.103 g (93%). C20H14N3O2, yellow crystals. Mp >300 ꢀC (CH3CN, decomp.); IR
(KBr): ꢀmax 3399, 3331, 1599, 1472, 1209, 1187, 1133, 719 cm–1; 1H NMR (DMSO-d6,
600 MHz): d 11.97 (br s, 2H), 9.14 (br s, 2H), 8.56 (d, J ¼ 4.9 Hz, 1H), 8.47 (d, J ¼ 4.9 Hz,
1H), 8.39 (d, J ¼ 7.8 Hz, 1H), 8.31 (d, J ¼ 4.9 Hz, 1H), 7.97–7.96 (m, 1H), 7.86–7.84 (m,
1H), 7.61–7.58 (m, 1H), 7.37 (d, J ¼ 8.5 Hz, 1H), 7.31–7.28 (m, 1H), 6.78 (dd, J1 ¼ 2.4 Hz,
J2 ¼ 8.5, Hz, 1H) ppm; 13C NMR (DMSO-d6, 150 MHz): d 187.2, 153.6, 141.7, 139.0,
138.1, 137.1, 135.2, 130.8, 130.3, 128.8, 128.6, 121.9, 120.3, 120.0, 118.0, 114.1, 113.2,
112.9, 112.8, 106.6 ppm; HRMS calcd. for C20H14N3O2 [M þ H]þ 328.1086;
found 328.1081.
4. Conclusions
In conclusion, the first total synthesis of trigonostemine G and its derivatives are
reported. Using protected 5-hydroxyindole, its reaction with 1-formyl-b-carboline build-
ing blocks can be accomplished, and in further 2 steps oxidation and protecting group
removal among mild condition results in a convenient method for the preparation of
bioactive b-carboline alkaloids.
Disclosure statement
No potential conflict of interest was reported by the authors.
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