Formal synthesis of schulzeines B and C: A new route to Gurjar's lactams

Article abstract of DOI:10.1002/jccs.202000216

Described is a formal synthesis of racemic schulzeines B and C that intercepts intermediates developed by Gurjar and co-workers. The synthetic sequence features an annulative coupling of a ketimine and acrylic acid enabling the construction of the benzoquinolizidine nucleus in a highly convergent manner. We also examined a continuous-flow version of the thermal aza-annulation, which proved less practical as compared to the batch processes.

Full text of DOI:10.1002/jccs.202000216

Received: 21 May 2020
Accepted: 15 July 2020
DOI: 10.1002/jccs.202000216
S P E C I A L I S S U E P A P E R
Formal synthesis of schulzeines B and C: A new route to
Gurjar's lactams
Chu-En Chou | Yi-An Chen | Yi-Ching Lin | Shih-Chieh Kao |
Chieh-Yu Chang
| Yen-Ku Wu
Department of Applied Chemistry,
Abstract
National Chiao Tung University, Hsinchu,
Taiwan
Described is a formal synthesis of racemic schulzeines B and C that intercepts
intermediates developed by Gurjar and co-workers. The synthetic sequence
features an annulative coupling of a ketimine and acrylic acid enabling the
construction of the benzoquinolizidine nucleus in a highly convergent man-
ner. We also examined a continuous-flow version of the thermal aza-annula-
tion, which proved less practical as compared to the batch processes.
Correspondence
Yen-Ku Wu, Department of Applied
Chemistry, National Chiao Tung
University, 1001 University Road,
Hsinchu 30010, Taiwan.
Email: yenkuwu@nctu.edu.tw
Funding information
K E Y W O R D S
Ministry of Science and Technology,
Taiwan, Grant/Award Number:
MOST108-2636-M-009-003
2-piperidone, aza-annulation, benzoqionolizidine, marine alkaloid, schulzeine
1 | INTRODUCTION
into the synthesis of 1–3 and their derivatives. In the past
decades, a number of approaches have been successfully
α-Glucosidase is a hydrolase enzyme that selectively
degrades carbohydrates to release glucose, and hence
plays a vital role in oligosaccharide metabolism, glyco-
protein processing, and other biological pathways.[1] Evi-
dently, small molecules displaying potent inhibitory
activities against α-glucosidase have been considered of
enormous therapeutic potential for treating diabetes.[2]
While the iminosugar-based α-glucosidase-inhibiting
drugs have been developed such as acarbose, miglitol,
and voglibose, the search for the new chemotypes endo-
wed with an improved pharmacological profile is still
highly desirable.[3] In 2004, Fusetani and co-workers
reported that schulzeines A (1), B (2), and C (3) possess
potent inhibitory activities against α-glucosidase
(48–170 nM).[4] Compounds 1–3 are a new class of
marine alkaloids isolated from extracts of the marine
sponge Penares schulzei. The structure of schulzeines
implemented to construct the tricyclic core of these alka-
loids.[5] The design plans of these syntheses underscore
the strategic uses of Pictet-Spengler-type cyclization,
Bischler-Napieralski reaction, asymmetric allylic addi-
tion, aza-Claisen rearrangement, or dehydrative ami-
nation. The research endeavors devoted in the
aforementioned works has provided us a great inspiration
in formulating our synthesis plan. In order to facilitate
further structure–activity-relationship (SAR) studies, we
envisioned a facile and modular route to these bio-
medicinally relevant alkaloids is definitely advantageous.
Herein, we describe a formal synthesis of schulzeines B
(2) and C (3) by intercepting lactams 4 and 5 established
by Gurjar and co-workers.[5]
In our retrosynthesis design (Scheme 1), Gurjar's
lactams 4 and 5 were derived from a common achiral
intermediate A through a two-step process involving an
comprises of
a
benzo[a]quinolizidine framework
α-amination and
a
hydrogenation reaction. We
appending with a tri-O-sulfated C28 fatty acid side chain
(Figure 1). The promising bioactivities coupled with their
unique structural features have drawn research efforts
envisioned that a formal (3 + 3) aza-cycloaddition of a
ketimine B and acrylic acid derivatives could give rise to
the
benzo[a]quinolizidine
ring
system.[6]
The
J Chin Chem Soc. 2020;1–6.
http://www.jccs.wiley-vch.de
© 2020 The Chemical Society Located in Taipei & Wiley-VCH GmbH
1

2
CHOU ET AL.
FIGURE 1 Structures of schulzeines A (1), B (2), and
C (3) and Gurjar's lactams 4 and 5
SCHEME 2 Gram-scale synthesis of dihydroisoquinoline 9
Napieralski reaction furnished dihydroquinoline 9. Over-
all, this four-step sequence is scalable, efficient, and oper-
ationally simple.
We next investigated the key aza-annulation reaction by
exploiting Compound 9 and acrylic acid as the coupling
partners. Initially, we observed no noticeable reactions
occurred in refluxing ethanol, acetonitrile, or dioxane.
When the thermal reaction was conducted in p-xylene, the
desired annulation product 10 and a regioisomer 11 were
successfully obtained in 31 and 13% yields, respectively
(Table 1, entry 1). The yield of the 1,2-piperidinone could
be increased to 42% by using 2 equiv. of acrylic acid
(Entries 2–4). Interestingly, methyl acrylate, in lieu of
acrylic acid, proved to be an inferior three-carbon donor in
the transformation (entries 5 and 6). We also surveyed a
range of Lewis-acid additives (1 equiv. of ZnI2, FeCl3, SnCl4,
Sc[OTf]3, CeCl3, AgNO3, or LiClO4) in an attempt to alter
the ratio of 10 to 11, but the bond-forming events were
mostly terminated in these trials. This scenario implies that
the Lewis acids play a detrimental role in this reaction by
taming the nucleophilic nitrogen. A plausible mechanism
to account the formation of 10 and 11 was depicted in
Scheme 3. We presumed the enamine (i.e., the tautomer of
9) could engage with acrylic acid in two different reaction
pathways leading to the isomeric piperidone products.
Over the last decade, continuous flow technology has
proven highly relevant and beneficial to the production
of specialty chemicals and active pharmaceutical ingredi-
ents.[8] Even by comparing with laboratory-scale batch
processes, merits of the flow synthesis have been widely
acknowledged. Since enhanced heat transfer is one of the
commonly recognized features, we sought to examine a
flow edition of the thermal aza-annulation reaction with
a simple tubular reaction system (Scheme 4). Although
SCHEME 1 Retrosynthetic analysis of 4 and 5
intermediate B could be prepared from readily available
3,5-dialkoxybenzaldehyde, nitromethane, and an acyl
donor through a short sequence of reactions.
2 | RESULTS AND DISCUSSION
We commenced conducting the Henry reaction between
nitromethane and 3,5-dibenzyloxybenzaldehyde at 80ꢀC
(Scheme 2). However, we found the reaction is difficult
to scale up; the product was produced only in moderate
yields (50–70%) along with a fair amount of intractable
material. To our delight, the application of
ultrasonication greatly improved the reaction efficiency
whereby the gram-scale synthesis of nitrostyrene 6 could
be reproducibly achieved (92% yield).[7] An exhaustive
reduction of 6 with lithium aluminum hydride led to the
formation of the corresponding primary amine 7 in excel-
lent yield. An N-acetylation followed by a Bischler-

CHOU ET AL.
3
TABLE 1 Survey of conditions for the aza-annulationa
Time
(hr)
Yield%b
of 10
Yield%b
of 11
Entry
R
m
1
1
2
3
4
5
6
H
6
31
13
16
23
24
0
H
2
6
42
H
5
6
30
H
10
2
6
17
Me
Me
6
Trace
29
7
41
9
aThe reaction was conducted with 2.0 mmole of 9 under a nitrogen
SCHEME 5 Synthesis of Gurjar's lactams 4 and 5
atmosphere.
bIsolated yields.
The successful reduction of enamide 10 with sodium
cyanoborohydride[9] set the stage for the key α-amination
of the benzo[a]quinolizidine core (Scheme 5). Following
a procedure developed by Heimgartner et al.,[10] Boc-
amino group was smoothly introduced at the α-position
in moderate diastereoselectivity (~2.5:1 by crude NMR
analysis), furnishing a separable mixture of the titled
1
lactams. The spectral data (IR, H NMR, 13C NMR and
mass spectra) of 4 and 5 are consistent with those
reported by the Gurjar group, and therefore the formal
synthesis of schulzeines B and C was achieved.[5]
SCHEME 3 Proposed reaction courses to 10 and 11
3 | CONCLUSIONS
In conclusion, we have established the formal synthesis of
schulzeines B and C from simple building blocks. Taking
advantage of ultrasonication technique, the formation of
side products was notably suppressed in the Henry reaction.
The key aza-annulation was implemented in either batch
or flow mode; the batch process stands out as a reliable
access to the benzo[a]quinolizidine skeleton. The synthetic
efforts pave a way for a rapid assembly of a library of
schulzeine analogues, and have prompted an ongoing SAR
investigation. The results will be disclosed in due course.
SCHEME 4 Continuous-flow synthesis of 10 and 11
the conversion of 9 is rather fast, we found that Com-
pound 10 was isolated in low yield, and only a trace
amount of 11 was detected in the crude mixture by H
NMR. A quick survey of different residence times failed
to improve the results; no further optimization of the pro-
cess was performed. We presumed the enhanced heat
transfer under flow conditions unfavorably accelerates
the oligomerization of acrylic acid, thus hampering the
desired aza-annulation.
4 | EXPERIMENTAL
4.1 | General information
1
All air-sensitive reactions were carried out using oven-
dried glassware under N2 atmosphere. tetrahydrofuran,
toluene, and dichloromethane were purified by passage
over activated alumina using a commercial solvent

4
CHOU ET AL.
1
purification system. All other solvents and commercially
obtained reagents were used without further purification.
Reactions were monitored by TLC on silica gel 60 Å F254
plates visualized by UV and ceric ammonium molybdate
or potassium permanganate staining solution. Flash chro-
matography was performed on silica gel (particle size
40–63 μm). Melting points are uncorrected. NMR spectra
3467, 1,595 cm−1; H NMR (400 MHz, CDCl3) δ 7.49–7.29
(m, 10H), 6.52 (s, 1H), 6.48 (s, 2H), 5.04 (s, 4H), 2.95
(t, J = 6.8 Hz, 2H), 2.70 (t, J = 6.8 Hz, 2H); 13C NMR
(100 MHz, CDCl3) δ 160.09, 142.30, 137.00, 128.66, 128.06,
127.63, 108.19, 99.92, 70.12, 43.34, 40.39; HRMS (EI, [M]+)
for C22H23NO2 calcd. 333.1723, found: 333.1714.
1
were measured at 500 MHz for H spectra and 125 MHz
for 13C spectra and calibrated from residual solvent sig-
4.4 | Synthesis and spectral
characterization of Compound 8
1
nals (chloroform at 7.26 ppm for H spectra; chloroform
at 77.16 ppm for 13C spectra). Infrared spectra were mea-
sured on KBr salt plates. High-resolution mass spectros-
copy (HRMS) was performed on a TOF instrument with
EI in positive ionization mode.
Under N2 atmosphere, to a stirring solution of Compound
7 (2.01 g, 5.31 mmol) and Et3N (0.89 ml, 6.37 mmol) in
CH2Cl2 (15 ml) was slowly added acetic anhydride
(0.6 mmol, 3 equiv.). After stirring at room temperature for
3 hr, the resulting mixture was washed with water (20 ml
×2), and the water layers were separated and back-extracted
with EtOAc (20 ml ×3). The combined organic layers were
washed with brine, dried over anhydrous MgSO4, filtered,
and concentrated under reduced pressure. The residue was
purified by flash chromatography (CH2Cl2/MeOH = 50:1)
to afford 8 as a white solid (1.87 g, 95%). Rf = 0.2 (hexanes/
EtOAc = 1:1). IR (film): 3292, 1,651 cm−1; 1H NMR
(400 MHz, CDCl3) δ 7.46–7.28 (m, 10H), 6.51 (br s, 1H),
6.44 (s, 2H), 5.03 (s, 4H), 3.49 (q, J = 6.6 Hz, 2H), 2.74
(t, J = 6.6 Hz, 2H), 1.91 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 170.12, 160.02, 141.30, 136.73, 128.48, 127.90,
127.41, 107.81, 100.04, 69.89, 40.35, 35.75, 23.10; HRMS (EI,
[M]+) for C24H25NO3 calcd. 375.1829, found: 375.1822.
4.2 | Synthesis and spectral
characterization of Compound 6
A
mixture of 3,5-diphenoxybenzaldehyde (2.0 g,
6.3 mmol), ammonium acetate (1.0 g, 12 mmol), and
acetic acid (1.0 ml, 21.1 mmol) in nitromethane (10 ml,
260.8 mmol) was placed at 80ꢀC under sonication
(power = 200 W; operating frequency = 40 KHz). After
7 hr, the solution was cooled to room temperature, and
the excess of nitromethane was removed under reduced
pressure. Methanol was added to the residue, and the
resulting mixture was placed in refrigerator at −20ꢀC for
12 hr to permit a process of recrystallization. After a fil-
tration and rinsing with cold methanol, Compound 6 was
obtained as white crystals (2.09 g, 92%). Rf = 0.5 (hex-
anes/CH2Cl2 = 10:1). IR (film): 1593, 1,374, 1,347 cm−1
;
4.5 | Synthesis and spectral
characterization of Compound 9
1H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 13.6 Hz, 1H), δ
7.50 (d, J = 13.6 Hz, 1H), 7.46–7.29 (m, 10H), δ 6.75 (s,
3H), 5.06 (s, 4H); 13C NMR (100 MHz, CDCl3) δ 160.44,
139.09, 137.58, 136.27, 131.89, 128.79, 128.34, 127.57,
108.25, 105.90, 70.38; HRMS (EI, [M]+) for C22H19NO4
calcd. 361.1309, found: 361.1303.
Under N2 atmosphere, a stirring solution of 8 (1.87 g,
4.99 mmol), phosphoryl chloride (3.26 ml, 35 mmol) in tol-
uene (15 ml) was brought up to 90ꢀC (oil bath), and stirred
for 5 hr. After the reaction mixture was cooled to room
temperature, the solvent was removed under reduced pres-
sure. The resulting mixture was basified with 15%
NaOH(aq) until reaching pH = 10, and then extracted with
EtOAc (10 ml ×2). The combined organic layers were
washed with water (10 ml ×3), dried over anhydrous
MgSO4, filtered, and concentrated under reduced pressure
to afford 9 (1.69 g, 95%) as a dark purple solid. Rf = 0.2
4.3 | Synthesis and spectral
characterization of Compound 7
Under N2 atmosphere, to a suspension of lithium alumi-
num hydride (1.1 g, 28.9 mmol) in THF (12 ml) was added
a solution of 6 (2.09 g, 5.8 mmol) in THF (10 ml) at 60ꢀC
over 2 hr via a syringe pump. After stirring at 60ꢀC for
15 hr, the reaction was cooled to 0ꢀC and then quenched
by adding water (1.1 ml), 15% NaOH(aq) (1.1 ml) and water
(3.3 ml) sequentially at 15 min intervals. The resulting mix-
ture was filtered, dried over anhydrous MgSO4, and con-
centrated under reduced pressure to afford 7 as a yellow oil
(1.77 g, 92%). Rf = 0.5 (hexanes/CH2Cl2 = 10:1). IR (film):
(hexanes/ EtOAc = 1:1). IR (film): 1673 cm−1; H NMR
1
(400 MHz, CDCl3) δ 7.50–7.28 (m, 10H), 6.53 (s, 1H), 6.44
(s, 1H), 5.05 (s, 4H), 3.51 (t, J = 7.1 Hz, 2H), 2.60
(t, J = 7.1 Hz, 2H), 2.47 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 164.83, 161.41, 158.52, 142.60, 136.34, 136.12,
128.73, 128.70, 128.27, 127.71, 127.54, 113.31, 105.56, 99.25,
70.85, 70.20, 45.75, 27.92, 27.63; HRMS (EI, [M]+) for
C24H23NO2 calcd. 357.1723, found: 357.1725.

CHOU ET AL.
5
4.6 | Synthesis and spectral
characterization of Compounds 10 and 11
was basified by adding 15% NaOH(aq) until reaching
pH = 10, and then extracted with EtOAc (10 ml ×2). The
combined organic layers were washed with brine, dried
over anhydrous MgSO4, filtered, and concentrated under
reduced pressure. The residue was purified by flash chro-
matography (CH2Cl2/MeOH = 25:1) to afford 12 as a
brown solid (230 mg, 99%). Rf = 0.4 (hexanes/ EtOAc = 4:1).
IR (film): 1705 cm−1; 1H NMR (400 MHz, CDCl3) δ
7.53–7.31 (m, 10H), 6.51 (s, 1H), 6.38 (s, 1H), 5.10–5.02
(m, 4H), 4.97–4.93 (m, 1H), 4.80–4.76 (m, 1H), 2.97–2.35
(m, 6H), 1.86–1.80 (m, 2H), 1.41–1.22 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 170.34, 158.30, 156.67, 138.30, 136.92,
128.79, 128.77, 128.21, 128.13, 127.67, 127.10, 118.61,
106.10, 99.17, 70.19, 70.10, 54.45, 38.68, 31.86, 30.62, 30.11,
19.68; HRMS (EI, [M]+) for C27H27NO3 calcd. 413.1985,
found: 413.1987.
[The Batch Procedure] Under N2 atmosphere, to a
refluxing solution of 9 (1.07 g, 3 mmol) in p-xylene
(30 ml) was added acrylic acid (0.41 ml, 6 mmol) over
1 hr via a syringe pump. After stirring at 150ꢀC for 6 hr,
the resulting mixture was washed with water (20 ml ×2).
The water layers were back-extracted with EtOAc (20 ml
×3). The combined organic layers were washed with
brine, dried over anhydrous MgSO4, filtered, and concen-
trated under reduced pressure. The residue was purified
by flash chromatography (CH2Cl2/MeOH = 25:1) to
afford 10 (520 mg, 42%) and 11 (200 mg, 16%). [The Flow
Procedure] A p-xylene solution (0.1 M, 1 ml) of Com-
pound 9 (0.1 mmol, 35.7 mg), acrylic acid (2 equiv.,
13.7 μl) was prepared and then pumped into a stainless-
steel tubing reactor (flow rate: 1.433 μl/min; volume:
0.086 ml; i.d.: 0.1 cm) that was placed in a sand bath
(130ꢀC). The reaction mixture eluted from the outlet was
discarded for the first 8.3 min (11.9 μl) and the subse-
quent portion was collected for 505.2 min (724 μl). The
crude mixture was purified by flash column chromatog-
raphy (CH2Cl2/MeOH = 25:1) to give 10 (5 mg, 12%). 10:
Brown solid. Rf = 0.4 (hexanes/ EtOAc = 4:1). IR (film):
4.8 | Synthesis and spectral
characterization of Compounds 4 and 5
A solution of lithium diisopropylamide (LDA) was pre-
pared by slowly adding 2.5 M n-butyl lithium (0.2 ml,
0.5 mmol) to a stirring solution of diisopropylamine
(0.08 ml, 0.06 mmol) in THF (5 ml) at −78ꢀC. After
15 min, the LDA solution was transferred to a solution of
10 (0.18 g, 0.5 mmol) at −78ꢀC over 15 min via a syringe
pump. The resulting mixture was stirred at −78ꢀC for
1
1695, 1,645, 1,602 cm−1; H NMR (400 MHz, CDCl3) δ
7.52–7.31 (m, 10H), 6.55 (s, 1H), 6.41 (s, 1H), 6.27
(t, J = 7.3 Hz,) 5.09 (s, 2H), 5.04 (s, 2H), 3.82 (t, J = 5.8 Hz,
2H), 2.79 (t, J = 5.8 Hz, 2H), 2.56 (t, J = 7.3 Hz, 2H), 2.36
(dt, J = 7.3 Hz, 2H); 13C NMR (100 MHz, CDCl3) δ
170.50, 158.65, 157.38, 138.81, 136.74, 136.72, 131.48,
128.81, 128.76, 128.28, 128.14, 127.66, 127.35, 113.78,
107.92, 105.82, 100.24, 70.94, 70.27, 38.90, 31.57, 30.69,
20.09; HRMS (EI, [M]+) for C27H25NO3 calcd. 411.1829,
found: 411.1825. 11: Brown solid. Rf = 0.4 (hexanes/
1
hr. Diphenylphosphoryl azide (DPPA; 0.12 ml,
0.55 mmol) was then added, and the mixture was stirred
for another 0.5 hr. After adding di-tert-butyl dicarbonate
(0.23 ml, 1.0 mmol), the reaction was allowed to warm to
room temperature. After 7 hr, 1 M NH4Cl(aq) (1 ml) was
added to quench the reaction, and the mixture was
extracted with EtOAc (10 ml ×2). The combined organic
layers were washed with brine, dried over MgSO4, fil-
tered, and concentrated under reduced pressure. The resi-
due was purified by flash chromatography (hexanes/
EtOAc = 1:1) to give Compounds 4 (130 mg, 51%) and
5 (50 mg, 19%). 4: Brown solid. Rf = 0.4 (hexanes/
EtOAc = 4:1). IR (film): 3401, 1712, 1,647,1,607 cm−1; 1H
NMR (400 MHz, CDCl3) δ 7.45–7.30 (m, 10H), 6.51 (s,
1H), 6.37 (s, 1H), 5.35 (br s, 1H), 5.03–4.90 (m, 4H),
4.96–4.90 (m, 1H), 4.81–4,78 (m, 2H), 4.13–3.93 (m, 1H),
3.09–2.74 (m, 2H), 2.66–2.42 (m, 3H), 1.87–1.67 (m, 2H),
1.46 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 168.90,
158.32, 156.90, 156.29, 138.03, 136.85, 136.59, 128.80,
128.75, 128.20, 127.63, 127.25, 118.47, 106.21, 99.25,
79.66, 70.30, 70.25, 56.27, 52.89, 39.66, 30.73, 28.50, 28.14;
HRMS (EI, [M]+) for C32H36N2O5 calcd. 528.2619, found:
528.2610. 5: Brown solid. Rf = 0.4 (hexanes/ EtOAc = 4:1).
EtOAc = 4:1). IR (film): 1736, 1,602, 1,580 cm−1 1H
;
NMR (400 MHz, CDCl3) δ 7.44–7.29 (m, 10H), 6.47
(s, 1H), 6.39 (s, 1H), 6.34 (s, 1H), 5.12 (br s, 2H), 4.99
(br s, 2H), 3.60 (m, 2H), 3.28 (m, 2H), 2.84 (m, 2H), 2.54
(m, 2H); 13C NMR (100 MHz, CDCl3) δ 192.36, 160.83,
159.03, 155.65, 140.27, 140.25, 136.16, 136.15, 128.66,
128.21, 127.89, 127.46, 126.82, 112.45, 106.19, 100.44,
100.25, 70.79, 70.07, 51.40, 48.34, 36.19, 30.92; HRMS (EI,
[M]+) for C27H25NO3 calcd. 411.1829, found: 411.1824.
4.7 | Synthesis and spectral
characterization of Compound 12
Under N2 atmosphere, to a stirring solution of 10
(230 mg, 0.66 mmol) in acetic acid (6 ml) was added
sodium cyanoborohydride (0.12 g, 1.98 mmol). After stir-
ring at room temperature for 3 hr, the reaction mixture
IR (film): 3407, 1714, 1,658, 1,608 cm−1
;
1H NMR
(400 MHz, CDCl3) δ 7.45–7.30 (m, 10H), 6.48 (s, 1H), 6.38

6
CHOU ET AL.
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(s, 1H), 5.74 (s, 1H), 5.07 (s, 2H), 5.00 (s, 2H), 4.95–4.87
(m, 1H), 4.77–4.69 (m, 1H), 4.35–4.30 (m, 1H), 2.87–2.48
(m, 5H), 1.46 (s, 9H), 1.41–1.37 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 170.59, 158.43, 155.93, 155.76,
137.28, 136.70, 136.45, 129.75, 128.79, 128.62, 128.13,
128.08, 127.50, 127.13, 117.35, 105.81, 99.01, 79.47, 70.14,
49.76, 48.80, 38.85, 29.72, 28.50, 28.39; HRMS (EI, [M]+)
for C32H36N2O5 calcd. 528.2619, found: 528.2610.
ACKNOWLEDGMENTS
We thank the Young Scholar Fellowship Program by the
Ministry of Science and Technology in Taiwan
(MOST108-2636-M-009-003) for financial support of this
work. We also thank Dr Li-Ching Shen for assistance
with NMR experiments.
ORCID
Chieh-Yu Chang https://orcid.org/0000-0002-5638-
482X
Yen-Ku Wu https://orcid.org/0000-0002-9269-7444
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SUPPORTING INFORMATION
Additional supporting information may be found online
in the Supporting Information section at the end of this
article.
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How to cite this article: Chou C-E, Chen Y-A,
Lin Y-C, Kao S-C, Chang C-Y, Wu Y-K. Formal
synthesis of schulzeines B and C: A new route to
Gurjar's lactams. J Chin Chem Soc. 2020;1–6.
https://doi.org/10.1002/jccs.202000216