Integrating Biomass into the Organonitrogen Chemical Supply Chain: Production of Pyrrole and d-Proline from Furfural

Article abstract of DOI:10.1002/anie.202006315

Production of renewable, high-value N-containing chemicals from lignocellulose will expand product diversity and increase the economic competitiveness of the biorefinery. Herein, we report a single-step conversion of furfural to pyrrole in 75 % yield as a key N-containing building block, achieved via tandem decarbonylation–amination reactions over tailor-designed Pd?S-1 and H-beta zeolite catalytic system. Pyrrole was further transformed into dl-proline in two steps following carboxylation with CO₂ and hydrogenation over Rh/C catalyst. After treating with Escherichia coli, valuable d-proline was obtained in theoretically maximum yield (50 %) bearing 99 % ee. The report here establishes a route bridging commercial commodity feedstock from biomass with high-value organonitrogen chemicals through pyrrole as a hub molecule.

Full text of DOI:10.1002/anie.202006315

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: Integrating Biomass into Organonitrogen Chemical Supply Chain:
Production of Pyrrole and D-Proline from Furfural
Authors: Song Song, Vincent Fung Kin Yuen, Lu Di, Qiming Sun, Kang
Zhou, and Ning Yan
This manuscript has been accepted after peer review and appears as an
Accepted Article online prior to editing, proofing, and formal publication
of the final Version of Record (VoR). This work is currently citable by
using the Digital Object Identifier (DOI) given below. The VoR will be
published online in Early View as soon as possible and may be different
to this Accepted Article as a result of editing. Readers should obtain
the VoR from the journal website shown below when it is published
to ensure accuracy of information. The authors are responsible for the
content of this Accepted Article.
To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202006315
Link to VoR: https://doi.org/10.1002/anie.202006315

10.1002/anie.202006315
Angewandte Chemie International Edition
COMMUNICATION
Integrating Biomass into Organonitrogen Chemical Supply Chain:
Production of Pyrrole and D-Proline from Furfural
Song Song, Vincent Fung Kin Yuen, Lu Di, Qiming Sun, Kang Zhou,* and Ning Yan*
Abstract: Production of renewable, high-value N-containing
chemicals from lignocellulose will expand product diversity and
increase the economic competitiveness of biorefinery. Herein, we
report a single-step conversion of furfural to pyrrole in 75% yield as a
key N-containing building block, achieved via tandem
decarbonylation-amination reactions over tailor-designed Pd@S-1
and H-beta zeolite catalytic system. Pyrrole was further transformed
into DL-proline in two steps following carboxylation with CO2 and
In the downstream side of the organonitrogen chemical supply
chain, L/D-proline[6] is a representative example extensively
used either directly,[7] or as precursor for pharmaceuticals. Its
market is expected to grow at an annual rate of 5.3% over the
next five years, and to reach US$ 310 million in 2025.[8]
Industrially, L-proline is produced via fermentation with glucose
as the substrate.[9] However, no fermentation process has been
reported for direct D-proline production. Racemic proline can be
hydrogenation over Rh/C catalyst. After treating with Escherichia coli, chemically synthesized from petroleum-based diethyl malonate
valuable D-proline was obtained in theoretically maximum yield
(50%) bearing 99% ee. The report here establishes a route bridging
commercial commodity feedstock from biomass with high-value
organonitrogen chemicals through pyrrole as a hub molecule.
with acrylonitrile through complex processes with at least 5
steps. At present, renewable and cost-effective method for D-
proline production is scarce. Since D-proline is a critical
precursor for important chemicals such as (-)-secu’amamine A
and (R)-harmicine,[10] and is a useful catalyst to access many
chiral molecules,[11] new protocols for producing D-proline from
renewable starting materials is desirable.
Bio-based furans, being commercially available and affordable
(e.g., 1.1-1.3 US$ kg-1 for furfural),[12] are among the most
promising feedstock to establish the organonitrogen chemical
supply chain in biorefinery. The structural similarity of pyrrole
and D-proline with furans prompted us to explore chemical
routes to bridge them. Herein, we communicate the direct
transformation of furfural into pyrrole, which, as a hub molecule,
is further converted into high-value D-proline (Figure. 1). For
pyrrole synthesis, aldehyde groups in furfural are removed and
oxygen in the furan ring is replaced by nitrogen using NH3 via
Lignocellulose is the most abundant and renewable biomass on
Earth. Previous work mainly focused on the production of
various hydrocarbons and oxygen-containing chemicals.[1]
Expanding the product scope beyond C-, O-, H- bearing
compounds will diversify the biorefinery economy. Nitrogen-
containing chemical synthesis via C-N bond formation
represents a new opportunity in biomass valorization due to the
nitrogen deficient nature of lignocellulose. There have been
excellent advances along this direction in recent years,[2] but
more remain to be developed considering the large number of
organonitrogen chemicals used in industry and daily life.
The main pathway to make organonitrogen chemicals in
current industry involves C-H activation of hydrocarbons to
introduce oxygen functionality followed by incorporation of
nitrogen functionalities to obtain N-containing chemicals. These
primary organonitrogen chemicals serve as building blocks for a
broad range of downstream products. Pyrrole is an important
primary N-containing chemical extensively used as precursors
for fine chemicals, drugs, catalysts and materials.[3] The classic
protocol for pyrrole synthesis is through oxidation of 1,3-
butadiene into furan followed by an additional amination
reaction.[4] Starting from chitin, pyrrole was also obtained but the
yield was only around 10%.[5]
one-step decarbonylation-amination reaction over
a tailor-
designed catalytic system. Following carboxylation using CO2
and hydrogenation of the furan ring, racemic proline was
obtained in high yield, which was kinetically resolved with E. coli
to produce pure D-proline.
[*]
Dr. S. Song, V. Fung, Dr. Q. Sun, Prof. Dr. K. Zhou, Prof. Dr. N. Yan
Department of Chemical & Biomolecular Engineering
National University of Singapore
4 Engineering Drive 4, Singapore 117585 (Singapore)
E-mail: ning.yan@nus.edu.sg
E-mail: kang.zhou@nus.edu.sg
Dr. L. Di
School of Materials Science and Engineering
Nankai University
38 Tongyan Road, Haihe Educational Park, Tianjin 300350 (P. R.
China)
Supporting information for this article is given via a link at the end of
the document.
Figure 1. A simplified overview of how organochemicals are made from
petroleum resources, the proposed organonitrogen chemical supply chain in
biorefinery, and the scope of current work.
This article is protected by copyright. All rights reserved.

10.1002/anie.202006315
Angewandte Chemie International Edition
COMMUNICATION
furfural decarbonylation, the furan ring was strongly adsorbed on
the Pd surface. However, the preferential adsorption of aldehyde
group on Pd surface may be enhanced after NH3 injection, which
increased the hydrodeoxygenation of furfural to 2-methylfuran.[14]
Scheme 1. Reaction network for single-step conversion of
furfural to pyrrole in the presence of NH3 and H2.
To our knowledge, single-step decarbonylation-amination of
furfural into pyrrole in the presence of NH3 and H2 (Scheme 1)
has not been achieved so far. Previously, Pd-based catalysts
have been reported effective for furfural decarbonylation to
furan,[13] but the effect of NH3 remains unknown. Thus, we
started by comparing furfural decarbonylation in the absence
and presence of NH3. Several commercial and home-made Pd-
catalysts (Pd/TiO2, Pd/SiO2, Pd/Al2O3, Pd/AC and Pd@S-1)
were tested. The major difference between the first four
catalysts and the last Pd@S-1 catalyst is that Pd NPs are
exposed on the exterior surface of supports in the former, while
encapsulated and confined in the zeolite pores in the latter (see
graphic views in Figure 2a-2b). In the absence of NH3, >90%
furfural conversion and ~90% furan selectivity were observed
over Pd/SiO2, Pd/Al2O3, Pd/AC and Pd@S-1 catalysts under
optimized condition, while Pd/TiO2 provided substantially lower
conversion (41%) and exclusive formation of 2-methylfuran as
an undesired product (Figure 2c, S1 and Scheme S1). The
strong metal-support interaction (SMSI) over Pd/TiO2, as
observed in XPS analysis (Figure S2), may change the furfural
adsorption mode, thereby switching the reaction pathway from
decarbonylation to hydrodeoxygenation (Figure 2c).
Significant catalyst deactivation was observed over all four
supported Pd catalysts after the injection of NH3 (Figure 2d). The
furfural conversion decreased from 92%, 100% and 100% to
65%, 80% and 97% over Pd/SiO2, Pd/Al2O3 and Pd/AC catalysts,
respectively, after 3 h time-on-stream (TOS), and decreased
further after 6 h TOS (Figure S3). The loss in catalytic activity is
partially attributed to competitive adsorption of NH3 as
suggested by in situ FTIR study using CO as a probe molecule
(Figure S4), and partially to the increase of coke formation in the
presence of NH3, as evidenced by thermogravimetric analysis
(TGA) (Figure S5). The amount of coke formation in Pd/SiO2
catalyst in the presence of NH3 was almost 3 times higher
compared to that without NH3. Similarly, the coke amount
increased around 30% over Pd/Al2O3 catalyst after introducing
NH3. The product distributions also changed significantly. When
NH3 was added, 2-furonitrile and 2-methylfuran appeared as
main side products over Pd/TiO2, Pd/SiO2, Pd/Al2O3 and Pd/AC
catalysts (Figure 2d). The formation of 2-furonitrile could be due
to the loss in decarbonylation activity and consequently the
unconverted furfural reacted with NH3 to form imine and finally
nitriles. The selectivity toward 2-methylfuran increased after
introducing NH3, especially for the Pd/AC catalyst. During
Figure 2. Graphic view of Pd@S-1 and other Pd-based catalysts.
a) Pd@S-1; b) Pd on other supports. NH3 effect on conversion
(dots) and product distribution (bars) for gas-phase furfural
decarbonylation. c) No NH3; d) With NH3. Reaction conditions:
catalyst 100 mg, furfural weight hourly space velocity (WHSV) =
0.2 h-1, NH3 0 or 4 ml/min, H2 20 ml/min, T = 350 °C, 1 bar, TOS
= 3 h.
Encapsulation of ultra-small metal nanoparticles inside zeolite
channels to form core-shell structures (metal@zeolite) is an
effective strategy for synthesizing highly selective and active
metal catalysts.[15] In opposition to the fast deactivation and low
selectivity of commercial Pd catalyst in furfural decarbonylation
in the presence of NH3, NH3 had little influence on the catalytic
performance of Pd@S-1 (Figure 2c, 2d). The furan yield
remained >90%. TGA results showed that Pd@S-1 catalyst was
highly resistant against coke formation (< 1%) regardless of the
NH3 concentration in the feed, which explains the stable catalytic
activity (Figure S5). The lower coke formation over Pd@S-1
catalyst was mainly attributed to the negligible acidity nature of
the silica support, the suitable pore channel structure for furans
to diffuse,[13a] and its exceptional NH3-resistant activity. The high
selectivity towards furan in the presence of NH3 may also due to
the pore confinement effect.[13a] No obvious Pd metal particle
aggregation was observed after reaction or regeneration (Figure
S6). From above, Pd@S-1 is a robust and suitable catalyst for
furfural decarbonylation to furan under NH3 atmosphere
compared to common, commercially available Pd catalysts.
Next, we studied the one-step conversion of furfural to pyrrole.
Considering the amination of furan to pyrrole is promoted by
acids, different types of solid acid catalysts, including γ-Al2O3,
SiO2-Al2O3, HZSM-5, H-beta and H-USY, were chosen and
combined with Pd@S-1 to demonstrate the viability of the single-
This article is protected by copyright. All rights reserved.

10.1002/anie.202006315
Angewandte Chemie International Edition
COMMUNICATION
Table 1: Conversions and product distributions over different catalyst combinations for one-step furfural to pyrrole.
Product selectivity [%]
Carbon
Conv. [%]
Entry
Cat. 1
Cat. 2
balance [%]
Others
1[a]
2[b]
3[b]
4[b]
5[b]
6[b]
Pd@S-1
Pd@S-1
Pd@S-1
Pd@S-1
Pd@S-1
Pd@S-1
None
100
100
100
100
100
100
0
91
74
81
13
23
45
0
0
0
0
6
7
9
90
89
87
89
86
83
SiO2-Al2O3 (1.8)[c]
γ-Al2O3
11
5
15
14
12
11
6
H-beta (25)[c]
H-ZSM-5 (25)[c]
H-USY (14)[c]
75
60
42
[a] Reaction conditions: 100 mg catalyst 1, furfural WHSV = 0.2 h-1, H2 20 ml/min, T = 350 °C, 1 bar, TOS = 3 h. [b] Reaction conditions: 100 mg catalyst 1, 100
mg catalyst 2, furfural WHSV = 0.1 h-1, NH3 12 ml/min, H2 20 ml/min, T = 460 °C, 1 bar, TOS = 3 h. [c] SiO2/Al2O3 ratio.
step conversion strategy. Furan amination required 400-450 °C
to occur,[16] but higher temperature (> 350 °C) was not suitable
for furfural decarbonylation. Almost 40% carbon was lost when
the reaction temperature was 400 °C (Figure S1). Hence,
Pd@S-1 and solid acid catalysts were loaded into two different
zones in the fixed-bed reactor to satisfy reaction conditions
To demonstrate biomass derived pyrrole could serve as a hub
molecule to access more value-added chemicals, we designed a
two-step protocol to convert pyrrole into DL-proline (Figure 3).
The first step is base-promoted carboxylation using CO2, which
has been studied but the product yield was around 40%.[17] We
tested the effectiveness of different inorganic bases (Table S5,
required for each step, with detailed scheme shown in Figure S7. entries 1-8), and the best activity was observed when K2CO3
With the adoption of dual layers in which the solid acid catalyst
layer has a higher temperature than the Pd@S-1 layer, the
carbon balance reached ~90% (Table 1). No pyrrole was
observed in the absence of acid catalyst (Table 1, entry 1), while
its selectivity was only 5% and 11% over γ-Al2O3 and SiO2-Al2O3
catalysts, respectively (Table 1, entries 2-3). Zeolites exhibited
much higher activities than γ-Al2O3 and SiO2-Al2O3 (Table 1,
entries 4-6). Based on the NH3 temperature-programmed
desorption, zeolites were more acidic than γ-Al2O3 and SiO2-
Al2O3 (Figure S8) explaining the better performance. Indole was
detected as a side product when HZSM-5 or HUSY was used,
which formed via the Diels-Alder and dehydration reactions
between furan and pyrrole. The highest pyrrole selectivity (75%)
was observed over H-beta, possibly due to its medium acidity
among the selected solid acid catalysts. In a continuous test of
12 h, furfural conversion was stable and pyrrole selectivity
decreased slightly from 75% to 60% over the Pd@S-1/H-beta
multifunctional catalytic system. After regeneration at 550 °C for
4 h in air, the system fully resumed its original catalytic activity
(Figure S9).
was used, affording 21% pyrrole-2-carboxylic acid after 3 h at
120 °C under 40 bar CO2. Prolonging the reaction time to 24 h,
the yield increased to 32% (Table S5, entry 9). The effect of
reaction temperature and initial CO2 pressure were further
evaluated (Table S5, entries 9-15). The product yield increased
from 32% to 36% upon reducing the temperature from 120 °C to
100 °C, but dropped to 20% when further decreasing
temperature to 80 °C. A volcano-type activity trend was also
observed for initial CO2 pressure (Table S5, entries 11-15). At 20
bar, the yield of pyrrole-2-carboxylic acid was 28%. Increasing
the pressure to 55 bar and 70 bar, 45% and 63% yields were
obtained, respectively. The yield decreased to 38% when
increasing the initial CO2 pressure to 90 bar. Thus, the highest
yield of pyrrole-2-carboxylic acid obtained from the carboxylation
of pyrrole with CO2 was 63%. Following that, quantitative yield of
racemic DL-proline (98%) was obtained by hydrogenation using
a commercial Rh/C catalyst.
Since D-proline can not be directly obtained via the current
fermentation technologies, the kinetic resolution of DL-proline
was performed to remove L-proline from the mixture. We chose
E. coli for this study as it is a well-studied model micro-organism,
and it has been used to produce organonitrogen chemicals from
renewable feedstocks.[18] L-proline, but not D-proline, can serve
as a sole carbon and nitrogen source for wildtype E. coli.[19] Wild-
type E. coli contains a three-step L-proline utilization pathway,
which oxidises L-proline to L-glutamate. L-proline oxidation to L-
glutamate is catalysed by proline utilization A (PutA) protein,
which has both proline dehydrogenase and L-glutamate-5-
semialdehyde dehydrogenase activities (Figure 4a).[20] L-
glutamate is further deaminated into -ketoglutarate. Here, the
carbon flux can then be further directed to gluconeogenesis and
the pentose phosphate pathway, which are critical in producing
important building blocks for biomass formation. When biomass
Figure 3. Conversion of pyrrole to racemic proline.
Carboxylation reaction condition: pyrrole 2 mmol, K2CO3 10
mmol, H2O 2 mL, initial CO2 70 bar, T = 100 °C, t = 24 h.
Hydrogenation reaction condition: pyrrole-2-carboxylic acid 2
mmol, Rh/C 20 mg, i-PrOH 3 mL, H2 30 bar, T = 100 °C, t = 24 h.
This article is protected by copyright. All rights reserved.

10.1002/anie.202006315
Angewandte Chemie International Edition
COMMUNICATION
accumulates, more PutA are expressed to consume L-proline,
leaving D-proline behind. We inoculated wildtype E. coli
imino acid into DL-proline.[21] We validated the method by using
commercially available DL-proline (yield: 81%; ee >99%; Figure
S13). As such, two kinetic resolution methods are established to
obtain D- and L-proline, respectively.
BL21(DE3) strain in
a chemically defined medium with
commercially available L-proline, D-proline or DL-proline (5 g/L
each) as the sole carbon source (Figure 4b, S10-S11). After a
48-h aerobic incubation at 37 °C, L-proline was fully consumed
and cell density (OD600) of the E. coli strain reached ~3.8, while
the yield of D-proline from the kinetic resolution process was
99.4% (Figure 4b). Acetate, a commonly encountered aerobic
fermentation product, was not detected (detection limit: 0.1 g/L).
Based on materials balance, the consumed L-proline should be
converted into CO2 and biomass (e.g. nucleic acids, proteins
and lipids). As such, an effective kinetic resolution of DL-proline
by using E. coli fermentation is developed.
To summarize, we have developed renewable routes to
produce two value-added nitrogen-containing chemicals pyrrole
and D-proline from biomass-derived furfural via decarbonylation-
amination, carboxylation, hydrogenation and kinetic resolution.
This work showcases the possibility of establishing
organonitrogen chemical supply chain in biorefinery, via the
transformation of biomass derived feedstock into hub
organochemcials that can be diversified into a spectrum of end
products. It also provides an example for recovering original
stereo-structure of biomass, which was lost during the traditional
treatment process. A limitation of the current work is the loss of
CO (20% of carbon) in the first step. We attempted to produce
proline from 2-furoic acid and 2-methylfuran to prevent carbon
loss, but these two routes, so far, have not been successful
under applied conditions (Figure S14).
Acknowledgements
The authors thank the Tier-1 & Tier-2 projects from Singapore
Ministry of Education (R-279-000-462-112, R-279-000-479-112
and R-279-000-594-112) and the C4T Emerging Opportunities
Fund - EOF2 from Cambridge Centre for Advanced Research
and Education in Singapore Ltd (CARES) (R-279-000-604-592).
Dr. L. Di thanks the National Natural Science Foundation of
China (Grant 21905144). We thank Daniel Tan, Jeff Zhou,
Smaranika Panda and You-Kang Lim (NUS) for their
assisstance on the kinetic resolution experiments, as well as
Prof. Alexei A Lapkin and Dr. Zhen Guo (Cambridge & NUS) for
inspirational discussions.
Keywords: furfural • pyrrole • proline • decarbonylation-
amination • kinetic resolution
[1]
a) A. Corma, S. Iborra, A. Velty, Chem. Rev. 2007, 107, 2411-2502; b)
G. W. Huber, S. Iborra, A. Corma, Chem. Rev. 2006, 106, 4044-4098;
c) W. Schutyser, T. Renders, S. Van den Bosch, S.-F. Koelewijn, G.
Beckham, B. F. Sels, Chem. Soc. Rev. 2018, 47, 852-908; d) X. Wu, X.
Fan, S. Xie, J. Lin, J. Cheng, Q. Zhang, L. Chen, Y. Wang, Nat. Catal.
2018, 1, 772-780; e) L. Dong, L. Lin, X. Han, X. Si, X. Liu, Y. Guo, F. Lu,
S. Rudic, S. F. Parker, S. Yang, Y. Wang, Chem 2019, 5, 1521-1536.
a) E. M. Karp, T. R. Eaton, V. S. i Nogué, V. Vorotnikov, M. J. Biddy, E.
C. Tan, D. G. Brandner, R. M. Cywar, R. Liu, L. P. Manker, W. E.
Michener, M. Gilhespy, Z. Skoufa, M. J. Watson, O. S. Fruchey, D. R.
Vardon, R. T. Gill, A. D. Bratis, G. T. Beckham, Science 2017, 358,
1307-1310; b) G. Liang, A. Wang, L. Li, G. Xu, N. Yan, T. Zhang,
Angew. Chem. Int. Ed. 2017, 56, 3050-3054; c) M. Pelckmans, W.
Vermandel, F. Van Waes, K. Moonen, B. F. Sels, Angew. Chem. Int. Ed.
2017, 56, 14540-14544; d) W. Deng, Y. Wang, S. Zhang, K. M. Gupta,
M. J. Hülsey, H. Asakura, L. Liu, Y. Han, E. M. Karp, G. T. Beckham, P.
J. Dyson, J. Jiang, T. Tanaka, Y. Wang, N. Yan, Proc. Natl. Acad. Sci.
2018, 115, 5093-5098; e) I. Scodeller, S. Mansouri, D. Morvan, E.
Muller, K. de Oliveira Vigier, R. Wischert, F. Jérôme, Angew. Chem. Int.
Figure 4. Kinetic resolution of DL-proline. a) The schematic
drawing of consuming L-proline from DL-proline in wild-type E.
coli BL21(DE3); b) DL-proline as substrate. The size of the error
bars (SE, n=2) is smaller than the symbol sizes. Experiments
were performed as descirbed in Section 1.5 in SI.
[2]
We further demonstrated the integration of chemical and
biological steps. The isolated DL-proline from pyrrole-2-
carboxylic acid hydrogenation was used in the biological step to
produce D-proline. After 48 h, L-proline was depleted while no
D-proline was consumed, highlighting chemical and biological
transformations established in this study can be seamlessly
combined. (Figure S12).
If the production of L-proline is desired, D-proline can be
converted into L-proline via an imino acid by simultaneously
using a proline oxidase that only accepts D-proline as the
substrate, and sodium cyanoborohydride which reduces the
This article is protected by copyright. All rights reserved.

10.1002/anie.202006315
Angewandte Chemie International Edition
COMMUNICATION
Ed. 2018, 57, 10510-10514; f) A. Afanasenko, T. Yan, K. Barta,
Commun. Chem. 2019, 2, 127; g) C. Xie, J. Song, H. Wu, Y. Hu, H. Liu,
Z. Zhang, P. Zhang, B. Chen, B. Han, J. Am. Chem. Soc. 2019, 141,
4002-4009; h) H. Li, H. Guo, Y. Su, Y. Hiraga, Z. Fang, E. J. Hensen, M.
Watanabe, R. L. Smith, Nat. Commun. 2019, 10, 699; i) Y. Wang, S.
Furukawa, S. Song, Q. He, H. Asakura, N. Yan, Angew. Chem. Int. Ed.
2020, 59, 2289-2293.
c) N. Luo, T. Montini, J. Zhang, P. Fornasiero, E. Fonda, T. Hou, W. Nie,
J. Lu, J. Liu, M. Heggen, L. Lin, C. Ma, M. Wang, F. Fan, S. Jin, F.
Wang, Nat. Energy 2019, 4, 575-584.
[13] a) C. Wang, L. Wang, J. Zhang, H. Wang, J. P. Lewis, F. Xiao, J. Am.
Chem. Soc. 2016, 138, 7880-7883; b) W. Zhang, Y. Zhu, S. Niu, Y. Li, J.
Mol. Catal. A: Chem. 2011, 335, 71-81.
[14] a) V. Vorotnikov, G. Mpourmpakis, D. G. Vlachos, ACS Catal. 2012, 2,
2496-2504; b) S. H. Pang, C. A. Schoenbaum, D. K. Schwartz, J. W.
Medlin, Nat. Commun. 2013, 4, 2448.
[3]
[4]
S. Michlik, R. Kempe, Nat. Chem. 2013, 5, 140-144.
K. Hatada, M. Shimada, K. Fujita, Y. Ono, T. Keii, Chem. Lett. 1974, 3,
439-442.
[15] a) N. Wang, Q. Sun, J. Yu, Adv. Mater. 2019, 31, 1803966; b) S. M. Wu,
X. Y. Yang, C. Janiak, Angew. Chem. Int. Ed. 2019, 58, 12340-12354;
c) Y. Chai, W. Shang, W. Li, G. Wu, W. Dai, N. Guan, L. Li, Advanced
Science 2019, 6, 1900299.
[5]
X. Gao, X. Chen, J. Zhang, W. Guo, F. Jin, N. Yan, ACS Sustain. Chem.
Eng. 2016, 4, 3912-3920.
[6]
[7]
L. Szabados, A. Savoure, Trends Plant Sci. 2010, 15, 89-97.
B. List, R. A. Lerner, C. F. Barbas, J. Am. Chem. Soc. 2000, 122, 2395-
2396.
[16] L. Tao, Z. Wang, T. Yan, Y. Liu, H. He, Y. Cao, ACS Catal. 2016, 7,
959-964.
[8]
Marketwatch.com, ‘Global proline market is projected to reach at a
CAGR of 5.3% during 2020-2025: Eon Market Research’, 2020.
[Online]. Available: https://www.marketwatch.com/story/global-proline-
market-is-projected-to-reach-at-a-cagr-of-53-during-2020-2025-eon-
market-research-2020-04-06.
[17] a) E. Smissman, M. Graber, R. Winzler, J. Am. Pharm. Assoc. 1956, 45,
509; b) A. Radhakrishnan, A. Meister, J. Biol. Chem. 1957, 226, 559-
571.
[18] X. Ma, G. Gözaydın, H. Yang, W. Ning, X. Han, N. Y. Poon, H. Liang, N.
Yan, K. Zhou, Proc. Natl. Acad. Sci. 2020, 117, 7719-7728.
[19] a) J. M. Wood, J. Bacteriol. 1981, 146, 895-901; b) H. Sasaki, A. Takaki,
A. Oshima, A. Ishida, S. Nagata, Ann. Microbiol. 2007, 57, 265.
[20] Y. Zhou, W. Zhu, P. S. Bellur, D. Rewinkel, D. F. Becker, Amino Acids
2008, 35, 711-718.
[9]
K. Araki, Y. Takasawa, J. Nakajima, Agric. Biol. Chem. 1975, 39, 1193-
1200.
[10] a) P. Liu, S. Hong, S. M. Weinreb, J. Am. Chem. Soc. 2008, 130, 7562-
7563; b) C. S. Lood, A. M. Koskinen, Eur. J. Org. Chem. 2014, 2014,
2357-2364.
[21] T. M. Beard, N. J. Turner, Chem. Commun. 2002, 3, 246-247.
[11] D. Mandalapu, Synlett 2015, 26, 707-708.
[12] a) R. Mariscal, P. Maireles-Torres, M. Ojeda, I. Sádaba, M. L.
Granados, Energy Environ. Sci. 2016, 9, 1144-1189; b) Y. Nakagawa,
K. Takada, M. Tamura, K. Tomishige, ACS Catal. 2014, 4, 2718-2726;
This article is protected by copyright. All rights reserved.

10.1002/anie.202006315
Angewandte Chemie International Edition
COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
Layout 1:
COMMUNICATION
Nitrogen-containing chemicals:
Production of renewable nitrogen-
containing chemicals (Pyrrole and D-
proline) from biomass-derived furfural
is achieved through a protocol
combining chemical and biological
process.
S. Song, V. Fung, L. Di, Q. Sun, K.
Zhou,* N. Yan*
Page No. – Page No.
Integrating Biomass into
Organonitrogen Chemical Supply
Chain: Production of Pyrrole and D-
Proline from Furfural
This article is protected by copyright. All rights reserved.