Discovery of a novel cathepsin inhibitor with dual autophagy-inducing and metastasis-inhibiting effects on breast cancer cells

Article abstract of DOI:10.1016/j.bioorg.2018.11.025

Drug resistance and cancer cells metastasis have been the leading causes of chemotherapy failure and cancer-associated death in breast cancer patients. In present, various active molecules either exhibiting novel mechanism of action such as inducing autophagy or inhibiting metastasis have been developed to address these problems. However, the compounds exhibiting such dual functions have rarely been described. Previous work in our group showed that TSA, as a synthetic analog of asperphenamate, induced autophagic cell death in breast cancer cells instead of apoptosis. Furthermore, the target enzyme of TSA was predicted to be cathepin L (Cat L) by natural product consensus pharmacophore strategy. Accumulated evidences have shown that cathepsins are closely associated with migration and invasion of breast cancer cells. It seemed likely that TSA-like molecules may possess the dual functions of inducing autophagy and inhibiting metastasis. Therefore, sixty optically active derivatives were firstly designed and synthesized by replacing the A-ring moiety of TSA with other substituted-phenyl sulfonyl groups. Further cathepsin inhibitory activity assay showed that (S, S) and (S, R) isomers displayed no activity against four kinds of cathepsins (L, S, K, B), while all derivatives tested were inactive toward K and B subtypes. Compound 6a with meta-bromo substituent displayed the greatest inhibitory activity, and its inhibitory capability against Cat L and S was 3.9 and 11.5-fold more potent than that of TSA, respectively. Molecular docking also exhibited that 6a formed more hydrogen bonds or π-π contacts with Cat L or S than TSA. In order to determine whether 6a could play dual roles, its anti-cancer mechanism was further investigated. On the one hand, MDC staining experiment and western blotting analysis validated that 6a can induce autophagy in MDA-MB-231 cells. On the other hand, its metastatic inhibitory ability was also confirmed by wound healing and transwell chamber experiment.

Full text of DOI:10.1016/j.bioorg.2018.11.025

Accepted Manuscript
Discovery of a novel cathepsin inhibitor with dual autophagy-inducing and
metastasis-inhibiting effects on breast cancer cells
Lei Yuan, Jun Liu, Wenhui He, Youmei Bao, Lei Sheng, Chunyang Zou,
Baichun Hu, Wentao Ge, Yang Liu, Jian Wang, Bin Lin, Yanchun Li, Enlong
Ma
PII:
S0045-2068(18)31155-6
DOI:
https://doi.org/10.1016/j.bioorg.2018.11.025
YBIOO 2633
Reference:
Bioorganic Chemistry
To appear in:
Received Date:
Revised Date:
Accepted Date:
10 October 2018
5 November 2018
17 November 2018
Please cite this article as: L. Yuan, J. Liu, W. He, Y. Bao, L. Sheng, C. Zou, B. Hu, W. Ge, Y. Liu, J. Wang, B. Lin,
Y. Li, E. Ma, Discovery of a novel cathepsin inhibitor with dual autophagy-inducing and metastasis-inhibiting
effects on breast cancer cells, Bioorganic Chemistry (2018), doi: https://doi.org/10.1016/j.bioorg.2018.11.025
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers
we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and
review of the resulting proof before it is published in its final form. Please note that during the production process
errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Discovery of a novel cathepsin inhibitor with dual autophagy-inducing and
metastasis-inhibiting effects on breast cancer cells
a
b
e
a
c
a
Lei Yuan , Jun Liu a, Wenhui He , Youmei Bao , Lei Sheng , Chunyang Zou , Baichun Hu ,
Wentao Ge a, Yang Liu a, Jian Wang a, Bin Lin a, Yanchun Li d,*, Enlong Ma b,*
a Key Laboratory of Structure-Based Drug Design and Discovery (Shenyang Pharmaceutical University), Ministry
of Education, Shenyang 110016, PR China
b Department of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, PR China
c Department of Pharmacy, Liaoning Vocational College of Medicine, Shenyang 110101, PR China
d GLP Center, Shenyang Pharmaceutical University, Shenyang 110016, PR China
e School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, PR China
Abstract: Drug resistance and cancer cells metastasis have been the leading causes of chemotherapy failure and
cancer-associated death in breast cancer patients. In present, various active molecules either exhibiting novel
mechanism of action such as inducing autophagy or inhibiting metastasis have been developed to address these
problems. However, the compounds exhibiting such dual functions have rarely been described. Previous work in
our group showed that TSA, as a synthetic analog of asperphenamate, induced autophagic cell death in breast
cancer cells instead of apoptosis. Furthermore, the target enzyme of TSA was predicted to be cathepin L (Cat L)
by natural product consensus pharmacophore strategy. Accumulated evidences have shown that cathepsins are
closely associated with migration and invasion of breast cancer cells. It seemed likely that TSA-like molecules
may possess the dual functions of inducing autophagy and inhibiting metastasis. Therefore, sixty optically active
derivatives were firstly designed and synthesized by replacing the A-ring moiety of TSA with other
substituted-phenyl sulfonyl groups. Further cathepsin inhibitory activity assay showed that (S, S) and (S, R)
isomers displayed no activity against four kinds of cathepsins (L, S, K, B), while all derivatives tested were
inactive toward K and B subtypes. Compound 6a with meta-bromo substituent displayed the greatest inhibitory
activity, and its inhibitory capability against Cat L and S was 3.9 and 11.5-fold more potent than that of TSA,
respectively. Molecular docking also exhibited that 6a formed more hydrogen bonds or - contacts with Cat L or
S than TSA. In order to determine whether 6a could play dual roles, its anti-cancer mechanism was further
investigated. On the one hand, MDC staining experiment and western blotting analysis validated that 6a can
induce autophagy in MDA-MB-231 cells. On the other hand, its metastatic inhibitory ability was also confirmed
by wound healing and transwell chamber experiment.
Key words: cathepsin inhibitor; anti-metastatic effect; inducing autophagy; docking calculations; anti-breast cancer
effects.
1. Introduction
The cancer epidemiology data coming from the Cancer Statistics 2017 provided a reasonably
accurate portrayal of current situation of breast cancer. The statistics showed that 252,710 new
cases of breast carcinoma and 40,610 cancer deaths in 2017 are projected to occur in the United
States. Breast cancer still ranks as the number one cause of new cancer cases in women and the
second most common cause of cancer-related death after lung cancer [1].
Chemotherapy is one of the most important strategies used in breast cancer therapy which
* Corresponding author. E-mail address: enlong_ma20180718@126.com.
* Corresponding author. E-mail address: liyanchun1971@sina.com.

displays multiple actions, such as inhibiting tumor cell division, angiogenesis or inducing cell
death [2, 3]. Since most anti-breast cancer drugs induce apoptosis of tumor cells, breast cancer
cells have the tendency to become remarkably resistant to proapoptotic stimuli [4-6]. Meanwhile,
metastasis is also a major obstacle to effective cancer treatment with chemotherapeutic drugs and
has been the leading cause of breast cancer associated mortality [7, 8]. Obviously, drug resistance
and cancer cells metastasis have become the critical impediment to breast cancer treatment.
Therefore, double functional chemotherapeutic agents with both novel mechanisms of action
against apoptosis-resistant cancer cells and inhibiting cancer metastasis ability are urgently
needed.
Natural products are always visualized as an arsenal of battling against various diseases.
They exhibit a wide scope of significant biological effects and are always being used in the design
and discovery of the target-based drugs in the pharmaceutical field [9-12]. Certainly, they show
more important and tremendous contribution to novel anti-cancer drug development.
Asperphenamate is always paid attention by us because asperphenamate and its analogues
displayed a novel anticancer mechanism of action, fully inducing autophagic death in different
kinds of cancer cell lines [13-15] (Figure 1). In further work, we did our best to determine
cysteine cathepsin was the target enzyme of asperphenamate by a natural product consensus
pharmacophore strategy. The inhibitory effects of some previous synthetic analogs with more
potent activity than asperphenamate on Cat L, S, K and B were further studied. The results
showed that an A-ring tosyl substituted derivative, TSA (Figure 1), displayed the greatest potency
against Cat L [16].
Figure 1. The structues of asperphenamate and TSA.
Human cysteine cathepsins includes eleven members which can be secreted from lysosomes
into the extracellular milieu to degrade various extracellular matrix (ECM) proteins which
facilitate the invasion, angiogenesis and metastasis of tumor cells [17-20]. Accumulated evidences

have shown that cathepsins in human breast cancer are responsible for metastasis [21-25]. In view
that TSA targeted cathepsin, we hypothesized that it could also possess anti-metastatic ability. At
the same time, our previous study had revealed that TSA exhibited novel anti-tumor effect by
inducing autophagy instead of apoptosis. It indicated that A-ring sulfonyl-substituted derivatives
of asperphenamate may present both autophagy-inducing and metastasis-inhibiting effects on
tumor cells.
In this paper, we report the synthesis of A-ring phenylsulfonyl substituted analogues of TSA.
Furthermore, the inhibitory activity of all derivatives against Cat L, S, K and B were tested. From
this screen results, compound 6a was shown to possess the most potent activity and was further
used to explore its ability to both induce autophagy and inhibit metastasis in breast cancer cells.
2. Results and discussion
2.1 Chemistry.
Considering that toluenesulfonyl substituent in A-ring moiety of TSA contributed to the
inhibitory ability against cathepsin, other substitution-type phenylsulfonyl groups would be
chosen to replace the toluenesulfonyl fragment. Compounds 1-15 were synthesized by similar
approach with the previously published procedures illustrated in Scheme 1 [15]. Briefly,
phenylalaninol IM1 was prepared by directly reduction of optically pure phenylalanine with
NaBH4/I2 [26]. IM1 reacted with benzoyl chloride to give N-benzoyl-phenylalaninol IM2 in
presence of K2CO3 [27]. The key intermediate IM3 was synthesized by esterification of IM2 with
optically pure N-(tert-butoxycarbonyl)-phenylalanine (N-Boc-phenylalanine) using 1,
1’-carbonyldiimidazole (CDI) as condensation reagent. Treatment of IM3 with a 1.5 M solution of
hydrogen chloride gas in ethyl acetate yielded the deprotected product, which was then
sulfonylated to furnish the target derivatives 1-15.
†
†
†
†

Scheme 1: Reagents and conditions: (i) H2SO4, NaBH4, I2, THF, reflux, 98%; (ii) benzoyl chloride, K2CO3, MeOH,
rt, 95%; (iii) N-Boc-(L or D)-phenylalanine, CDI, CHCl3, rt, 70-87%; (iv) (a) 1.5 M HCl/ethyl acetate, rt, 77-90%;
(b) Different substituted phenylsulfonyl chlorides, triethylamine, CH2Cl2, rt, 91-96%.
2.2 Cathepsin inhibitory activity assay.
All derivatives were screened for their inhibitory activities toward Cat L, S, B and K. TSA
was chosen as control. The results were summarized in Table 1. All synthetic compounds were
inactive (IC50100 M) against Cat B and K. The (S, S) and (S, R) isomers 1-15c and d showed no
inhibitory effect on four cathepsins. Among all derivatives, the meta-bromo substituted derivative
6a showed the greatest potency against Cat L and S with an average IC50 value of 7.66±0.83 and
6.94±0.67 M, respectively. Unsubstituted derivatives 5 totally lost its inhibition ability against all
cathepsins.
As far as mono-substituted derivatives are concerned, ortho-bromo substituted analog 7 was
non-effective. With the exception of the 4-methoxyl substituted derivative 2, almost other
para-substituted (R, S) stereoisomers with electron-withdrawing group (F 4, Br 1, CF3 3) showed
inhibitory potency. Although, corresponding (R, R) isomers were inactive. Only the 4-fluoro
derivative 4a showed moderate inhibitory activity against Cat S and 3.6-fold decreased activity
compared with 6a.
Among di-substituted derivatives, the 2, 6-difluoro derivative 9 displayed no inhibitory
ability against four cathepsins. 5-Bromo-2-methoxyl derivative 10a was more potent than other
compounds and displayed a 1.6-fold and 4.6-fold decreased activity against Cat L and S compared
with 6a, respectively. And the 2, 5-dimethoxyl analog 11 also showed inhibitory effect but was
significantly less potent than 10a. Despite the fluoro and trifluoromethyl groups at 4-position still
remain, the inhibitory potency of compound 8 and 13 decreased evidently while the other
electron-withdrawing group was introduced into 2-position, such as fluoro and nitro groups.
Interestingly, although 4-position was substituted by methoxyl group with electron-donating effect,
the (R, S) and (R, R) isomers of the 2, 4-dimethoxyl analog 12 showed comparable activity with
10a against Cat L. The derivative 14b remained the inhibitory activity even after
electron-withdrawing groups were introduced at the 3- and 4-positions. Although the 2, 4-difluoro
derivative 8 showed weak inhibitory effect, tri-substituted derivative 15 showed moderate
inhibitory ability after chloro group was further introduced in 5-position of 8. In addition, only
10a and 15a displayed moderate inhibitory potency toward Cat S in all di- or tri-substituted

derivatives.
In general, both the electronic nature and the position of the substituents played important
roles in cathepsin inhibitory potency. It indicated that the substituents at the 2-position displayed a
significant impact on activity, which electron-donating groups being more beneficial to enzyme
inhibition effect than electron-withdrawing groups. Meanwhile, electron-withdrawing groups at
the 5-position are also contributive to activity.
(Table 1 should be listed here)
2.3 Docking study.
To discover potential cathepsin inhibitors, molecular docking was carried out to reveal the
interaction modes of A-ring phenylsulfonyl substituted derivatives in the active sites of Cat L and
S. Compound 6a, which displayed the most pronounced activity against Cat L and S, was selected
for the molecular docking studies. And as a control, the molecular docking of lead compound,
TSA, was also performed along with 6a. The crystal structures of Cat L (PDB ID: 2XU4) [28] and
S (PDB ID: 3OVX) [29] were used for the docking calculations [30].
For Cat L, the key residue Gly68 formed dual hydrogen-bond interactions with two
compounds. And the carbonyl oxygen in the B-ring region of TSA only made a hydrogen-bond
interaction with His163. Although, comparing with TSA, both amide oxygen and NH in the
B-ring moiety of 6a formed two hydrogen bonds with the backbone NH of Gln19 and carbonyl
oxygen of Asp162, respectively. And the meta-bromo group in 6a interacted with a hydrophobic
pocket being composed by Leu69, Met70 and Ala214 (Figure 2). For Cat S, hydrogen-bond
interactions appeared between residue Gly69 and two compounds. In the same time, their B-ring
moieties formed the other hydrogen-bond interactions which amide carbonyl oxygen of TSA
made a contact with residue His164, and amide NH of 6a formed an interaction with Asn163.
Both A and D-phenyl rings of TSA and 6a participated in the - contacts with Phe70. The
additional - interaction between B-phenyl ring of 6a and imidazolyl ring of His164 residue was
also observed (Figure 3).

Figure 2. 2D and 3D binding modes of TSA (a, purple stick), compounds 6a (b, brown stick) with Cat L. The Cat
L protein was displayed in ribbon and amino acid residues were displayed as blue thin stick.
Figure 3. 2D and 3D binding modes of TSA (a), compounds 6a (b) with Cat S. The Cat S protein was displayed in

ribbon and amino acid residues were displayed as blue thin stick.
The shape of binding pockets of Cat L and S were displayed as molecular surfaces (Figure 4
and 5). In Cat L, TSA and 6a exhibited key interactions with S1, S2 and S3 pockets [31] utilized
by their A- and C-phenyl rings. In addition, the B-rings of TSA and 6a interacted with S2’ pocket
being composed of Cys22, Gly23 and Cys25 residues and the S1’ pocket including Ala138,
Leu144 and Trp189 residues, respectively. Hydrophobic interactions of meta-bromo group seem
to alter the orientation of B-ring in 6a to make it interact with S1’ pocket. In Cat S, TSA and 6a
showed similar interactions. In addition to accommodation into S1, S2 and S3 pockets well [32],
they provided hydrophobic interactions with the side chains of Ala140, Phe146 and Trp186 by
their B-phenyl rings.
Figure 4. Binding modes of TSA (purple stick) and compound 6a (brown stick) with Cat L (blue surface).
Figure 5. Binding modes of TSA (purple stick) and compound 6a (brown stick) with Cat S (green surface).
In general, the docking results showed that 6a formed more hydrogen bonds than TSA with
Cat L. And for Cat S, 6a also displayed more - contacts than TSA. It was obvious that
molecular simulation results were consistent with the cathepsin inhibitory assay results. The
N-phenylsulfonyl-phenylalanine moiety was the key fragment whose A-and C-phenyl ring
occupied S2 and S3 pockets well, and the sulfonyl linker filled in the S1 pocket in Cat L and S.

The hydrophobic bromo atom at the 3-position in the A-ring of 6a made the B-ring more tightly
interact with S1’ rather than S2’ pocket, leading to an enhancement of inhibitory ability against
Cat L. It meant that S1’ hydrophobic pocket was the essential binding domain for this kind of
compound. However, the D-ring did not show any fixed interaction with Cat L and S. Due to the
D-ring being surrounded by the region composed of Cys65 and Asn66, we hypothesized that some
hydrogen-bond acceptors would provide more benefit for their interactions. Therefore, follow-up
work will focus on modification of the 3-position of the A-ring and introduction carbonyl and
cyano substituents into D-ring to further increase the interactions with cathepsin based on keeping
N-phenylsulfonyl-phenylalanine moiety.
2.4 Compound 6a suppressed breast cancer cells migration.
An increasing literature described the important role of cathepsin in tumor progression,
especially in the process of migration and invasion. Compared with primary tumor, the relative
activity of cathepsins in metastatic tumor significantly increased. Therefore, it indicates that
inhibition of cathepsins may be favorable in reducing the occurrence of tumor migration and
invasion. Our cathepsin inhibitory activity results displayed that compound 6a showed the greatest
potency against Cat L and S. And hence, its inhibitory activity against tumor migration and
invasion was further studied in two kinds of breast cancer cells, MCF-7 and MDA-MB-231.
2.4.1 6a and cathepsin inhibitor, E-64d had no effect on the proliferation of MDA-MB-231 and
MCF-7 cells.
Firstly, we determined the non-cytotoxic concentration of 6a by MTT assay for the purpose
of eliminating the impact of 6a on cell proliferation in the subsequent anti-migration and invasion
experiments. MDA-MB-231 and MCF-7 cells were treated with 6a at different concentrations of
3.125, 6.25 and 12.5 μM for 48 h, after which MTT assay were performed to evaluate the cell
viability.
Figure 6 displayed that 3.125-12.5 μM of 6a showed no anti-proliferative effect on two
types of breast cancer cell lines. Along with 6a, cathepsin inhibitor E-64d as control at the
concentration of 12.5 μM also exhibited no cytotoxity against two cells. Therefore, we defined
upper limit of concentration of 6a at 12.5 μM in following studies.

Figure 6. Cell viability of MDA-MB-231 and MCF-7 cells after treatment with 6a and E-64d.
2.4.2 Compound 6a inhibited breast cancer cells migration and invasion.
In order to investigate the effect of 6a on migration and invasion of the two breast cancer cell
lines, wound healing and transwell chamber assays were carried out. Previous research indicated
that MDA-MB-231 cells displayed stronger metastatic ability than MCF-7 cells [16]. Therefore,
MDA-MB-231 cells were chosen to study further.
MDA-MB-231 cells were incubated with DMSO, 6a (at 3.125, 6.25 and 12.5 μM,
respectively) and E64d at 12.5 μM for 48 h. Then, the anti-metastatic potential was examined by
the wound healing assay. As expected, breast cancer cells in DMSO control displayed the
strongest migratory ability. A dose-dependent inhibitory effect of 6a was observed in
MDA-MB-231 cells. The width of scratch directly reflected the decreasing migration capability of
MDA-MB-231 cells by 25%, 38% and 46% in correspondence to the concentrations of 6a. Its
migration inhibitory potency at 12.5 μM was close to E64d (Figure 7a).
On the other hand, transwell chamber assay results showed that compound 6a significantly
attenuated the ability of cells invasion by treating the cells using 6a at concentrations of 3.125,
6.25 and 12.5 μM. Under these conditions, the number of cells that permeated the membrane was
reduced by 18%, 36% and 47%, respectively. In conclusion, all results illustrated that 6a displayed
a significant anti-metastatic ability against MDA-MB-231 cells (Figure 7b).

Figure 7. Compound 6a inhibited migration of MDA-MB-231 cells. a. Wound healing assay; b. Transwell
chamber assay were used to investigate the effect of compound 6a on migration of MDA-MB-231 cells.
2.5 6a induced autophagy in MDA-MB-231.
Because our previous work showed that TSA was an autophagy inducer, we guessed that 6a as
an analog of TSA, could also possess autophagy-inducing potency. For the sake of determining
the suitable concentration of 6a in subsequent assay, antitumor activity of 6a against
MDA-MB-231 cells was screened in vitro through the standard MTT method using cisplatin as
control (see Table 1s). The results showed that the IC50 value for 6a was 26.24±1.43μM.
Accordingly, two concentrations (12.5 and 25 M) were selected for following study.
To investigate autophagy-inducing effect of 6a on MDA-MB-231 cells, we first observed the
morphological changes using fluorescence microscopy after MDC staining [33]. As shown in
Figure 8a, 12.5 and 25 M of 6a induced the formation of acidic vesicle organelles (a
characteristic of autophagy), suggesting that autophagy occurred in MDA-MB-231 cells 6a treated
[34]. The conversion of LC3-I to LC3-II was also examined so as to further assess the
development of autophagy in 6a-treated MDA-MB-231 cells [35]. Figure 8b showed that
autophagy marker LC3-II was detected by western blot analysis. These results proved that 6a can

induce autophagy in MDA-MB-231 cells.
Figure 8. 6a induced autophagy in MDA-MB-231 cells. a. Autophagosomes observation. MDA-MB-231 cells
treated with 6a (12.5 and 25 μM) for 72h, and then the cells were stained with MDC and observed by fluorescence
microscope; b. Western blotting analysis for autophagy. MDA-MB-231 cells were treated with 6a (12.5 and 25 μM)
for 72h, and then the total proteins were extracted and detected by western blot analysis.
3. Conclusion
In summary, sixty optically active derivatives of TSA were designed and synthesized. The
structures of all derivatives were characterized by NMR and HR-MS. Subsequent cathepsin
inhibitory assay showed compound 6a displayed the greatest inhibitory activity against both Cat L
and S. The enzyme inhibitory ability of 6a against Cat L and S was 3.9 and 11.5-fold more potent
than that of TSA, respectively. These results were also supported by molecular simulation study
that 6a formed more hydrogen bonds and - interactions with Cat L and S than TSA. In order to
determine whether 6a could possess the dual functions of inducing autophagy and inhibiting
metastasis, MDC staining experiment and western blotting analysis were firstly undertaken. The
overall results showed that 6a induced the autophagy in MDA-MB-231 cells. On the other hand,
evidence for the inhibitory effect of 6a on migration and invasion of breast cancer cells was
furthermore provided by wound healing and transwell chamber experiments.
4. Experimental
4.1. Reagents and apparatus
Melting points were measured by use of a Büchi Melting Point B-540 apparatus (Büchi

Labortechnik, Flawil, Switzerland) without correction. High resolution mass spectra were carried
out on a Bruker Micromass Time of Flight mass spectrometer using electrospray ionisation (ESI).
1H NMR and 13C NMR spectra were recorded on a Bruker ARX-600 (600 MHz). Unless
otherwise stated, reagents came from commercial sources and used without further purification.
All crude target compounds and intermediates were purified by chromatographic column using
silica gel (200-300 mesh) from Qingdao Ocean Chemicals with chloroform/acetone mixture as
eluent. The intermediates IM1, IM2 and IM3 were prepared followed by the methods in
references [26, 27, 15], respectively.
4.2 General procedure for the preparation of derivatives 1-15
To a solution of hydrogen chloride gas in dry ethyl acetate (1.5 M, 3.0 mL) was added
intermediate IM 3 (0.3 g, 0.6 mmol). The reaction mixture was stirred for 4 h at room temperature.
The solvent was removed under reduced pressure to give solid deprotected product. Various
substituted-phenyl sulfonyl chlorides were added dropwise in a mixture of deprotected product
and triethylamine (0.5 mL) in anhydrous CH2Cl2 (10 mL). After stirring at room temperature
overnight, the reaction mixture was concentrated using a rotary evaporator. The crude product was
purified by chromatography on silica gel utilized a mixture of chloroform and acetone (35:1, v/v)
as eluent to furnish the desired product.
4.2.1
(R)-(S)-2-Benzamido-3-phenylpropyl
2-(4-bromophenylsulfonamido)-3-phenyl
propanoate (1a)
mp 164-167 ºC; yield 63.9 %; [] 20 -23.3 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
D
1
C31H29BrN2O5SNa, calcd. 643.0878 [M+Na]+, found: 643.0878; H NMR (600 MHz, CDCl3): 
7.73-7.75 (d, J = 6.6 Hz, 2H, ArH), 7.42-7.50 (m, 7H, ArH), 7.18-7.32 (m, 8H, ArH), 7.00 (m, 2H,
ArH), 6.53 (d, 1H, J = 7.8 Hz, CONH), 5.18 (d, J = 9.0 Hz, 1H, CONH), 4.61 (m, 1H, 4-H),
4.34-4.36 (d, J = 9.6 Hz, 1H, 3a-H), 4.11 (d, J = 5.4 Hz, 1H, 2-H), 4.03 (dd, J = 7.2 Hz, 1H, 3b-H),
3.06-3.10 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.97-3.00 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.87-2.93
(dd, J = 13.8, 6.6 Hz, 2H, 1b-H, 5b-H); 13C NMR (150 MHz, CDCl3) δ 170.6, 167.1, 138.2, 136.9,
134.8, 134.0, 132.2×2, 131.6, 129.2×2, 129.0×2, 128.7×2, 128.7×2, 128.4×2, 128.4×2, 127.8,
127.3, 127.0×2, 126.8, 66.2, 57.3, 49.8, 38.7, 37.2.
4.3.2
(R)-(R)-2-Benzamido-3-phenylpropyl
2-(4-bromophenylsulfonamido)-3-phenyl
propanoate (1b)

1
mp 162-164 ºC; yield: 60.2 % ; []2D0 47.1 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.72-7.73 (d, J = 7.8 Hz, 2H, ArH), 7.41-7.52 (m, 7H, ArH), 7.19-7.34 (m, 8H, ArH),
7.02 (m, 2H, ArH), 6.45 (d, 1H, J = 8.4 Hz, CONH), 5.17 (d, J = 9.6 Hz, 1H, CONH), 4.59 (m,
1H, 4-H), 4.25-4.28 (dd, J = 11.4, 3.0 Hz, 1H, 3a-H), 4.17-4.21 (dd, J = 14.4, 8.4 Hz, 1H, 2-H),
4.12 -4.15 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.08-3.11 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.98-2.95
(dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.92-2.88 (dd, J = 13.8, 6.6 Hz, 1H, 1b-H), 2.83-2.87 (dd, J =
13.8, 6.6 Hz, 1H, 5b-H).
4.3.3
(S)-(R)-2-Benzamido-3-phenylpropyl
2-(4-bromophenylsulfonamido)-3-phenyl
propanoate (1c)
1
mp: 164-168 ºC; yield: 65.4 %; []2D0 22.8 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.73-7.75 (d, J = 6.6 Hz, 2H, ArH), 7.42-7.50 (m, 7H, ArH), 7.18-7.32 (m, 8H, ArH),
7.00 (m, 2H, ArH), 6.53 (d, 1H, J = 7.8 Hz, CONH), 5.18 (d, J = 9.0 Hz, 1H, CONH), 4.61 (m,
1H, 4-H), 4.34-4.36 (d, J = 9.6 Hz, 1H, 3a-H), 4.11 (d, J = 5.4 Hz, 1H, 2-H), 4.03 (dd, J = 7.2 Hz,
1H, 3b-H), 3.06-3.10 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.97-3.00 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H),
2.87-2.93 (dd, J = 13.8, 6.6 Hz, 2H, 1b-H, 5b-H).
4.3.4
(S)-(S)-2-Benzamido-3-phenylpropyl
2-(4-bromophenylsulfonamido)-3-phenyl
propanoate (1d)
1
mp: 162-163 ºC; yield: 64.9 %; []2D0 -46.6 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.72-7.73 (d, J = 7.8 Hz, 2H, ArH), 7.41-7.52 (m, 7H, ArH), 7.19-7.34 (m, 8H, ArH),
7.02 (m, 2H, ArH), 6.45 (d, 1H, J = 8.4 Hz, CONH), 5.17 (d, J = 9.6 Hz, 1H, CONH), 4.59 (m,
1H, 4-H), 4.25-4.28 (dd, J = 11.4, 3.0 Hz, 1H, 3a-H), 4.17-4.21 (dd, J = 14.4, 8.4 Hz, 1H, 2-H),
4.12 -4.15 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.08-3.11 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.98-2.95
(dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.92-2.88 (dd, J = 13.8, 6.6 Hz, 1H, 1b-H), 2.83-2.87 (dd, J =
13.8, 6.6 Hz, 1H, 5b-H).
4.3.5
(R)-(S)-2-Benzamido-3-phenylpropyl
2-(4-methoxyphenylsulfonamido)-3-phenyl
propanoate (2a)
mp: 158-160 ºC; yield: 61.1 %; [] 2D0 -17.5 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
C32H32N2O6SNa, calcd. 595.1879 [M+Na]+, found: 595.1880; 1H NMR (600 MHz, CDCl3):  7.75
(d, J = 7.8, 2H, ArH), 7.58 (d, J = 9.0, 2H, ArH), 7.40-7.50 (m, 3H, ArH), 7.18-7.32 (m, 8H, ArH),
7.04 (m, 2H, ArH), 6.82 (d, J = 9.0, 2H, ArH), 6.60 (d, 1H, J = 8.4 Hz, CONH), 5.10 (d, J = 9.0

Hz, 1H, CONH), 4.57 (m, 1H, 4-H), 4.32-4.34 (dd, J = 10.8, 3.0 Hz, 1H, 3a-H), 4.09-4.12 (dd, J =
14.4, 7.8 Hz, 1H, 2-H), 3.97-4.00 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.83 (s, 3H, 8-H), 3.03-3.06
(dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 2.94-2.98 (m, 2H, 5a-H, 1b-H), 2.82-2.86 (dd, J = 13.8, 7.8 Hz,
1H, 5b-H); 13C NMR (150 MHz, CDCl3) δ 171.6, 166.9, 163.0, 136.9, 134.9, 133.9, 131.6, 130.6,
129.2×2, 129.2×4, 128.7×2, 128.6×2, 128.5×2, 127.3, 127.0×2, 126.8, 114.1×2, 65.9, 56.8, 55.5,
50.2, 38.8, 37.0.
4.3.6
(R)-(R)-2-Benzamido-3-phenylpropyl
2-(4-methoxyphenylsulfonamido)-3-phenyl
propanoate (2b)
1
mp: 153-154 ºC; yield: 57.7 %; []2D0 34.8 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.75 (d, J = 7.2, 2H, ArH), 7.59 (d, J = 9.0, 2H, ArH), 7.42-7.52 (m, 3H, ArH),
7.20-7.32 (m, 8H, ArH), 7.05 (m, 2H, ArH), 6.82 (d, J = 9.0, 2H, ArH), 6.54 (d, 1H, J = 7.8 Hz,
CONH), 5.05 (d, J = 9.0 Hz, 1H, CONH), 4.54 (m, 1H, 4-H), 4.17-4.22 (m, 2H, 3a-H, 2-H),
4.07-4.09 (dd, J = 10.8, 3.6 Hz, 1H, 3b-H), 3.81 (s, 3H, 8-H), 3.04-3.07 (dd, J = 13.8, 6.0 Hz, 1H,
1a-H), 2.90-2.97 (m, 2H, 5a-H, 1b-H), 2.77-2.80 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.7
(S)-(R)-2-Benzamido-3-phenylpropyl
2-(4-methoxyphenylsulfonamido)-3-phenyl
propanoate (2c)
1
mp: 157-158 ºC; yield: 60.4 %; []2D0 17.3 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.75 (d, J = 7.8, 2H, ArH), 7.58 (d, J = 9.0, 2H, ArH), 7.40-7.50 (m, 3H, ArH),
7.18-7.32 (m, 8H, ArH), 7.04 (m, 2H, ArH), 6.82 (d, J = 9.0, 2H, ArH), 6.60 (d, 1H, J = 8.4 Hz,
CONH), 5.10 (d, J = 9.0 Hz, 1H, CONH), 4.57 (m, 1H, 4-H), 4.32-4.34 (dd, J = 10.8, 3.0 Hz, 1H,
3a-H), 4.09-4.12 (dd, J = 14.4, 7.8 Hz, 1H, 2-H), 3.97-4.00 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.83
(s, 3H, 8-H), 3.03-3.06 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 2.94-2.98 (m, 2H, 5a-H, 1b-H), 2.82-2.86
(dd, J = 13.8, 7.8 Hz, 1H, 5b-H);
4.3.8
(S)-(S)-2-Benzamido-3-phenylpropyl
2-(4-methoxyphenylsulfonamido)-3-phenyl
propanoate (2d)
1
mp: 153-154ºC; yield: 58.7 %; []2D0 -34.6 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.75 (d, J = 7.2, 2H, ArH), 7.59 (d, J = 9.0, 2H, ArH), 7.42-7.52 (m, 3H, ArH),
7.20-7.32 (m, 8H, ArH), 7.05 (m, 2H, ArH), 6.82 (d, J = 9.0, 2H, ArH), 6.54 (d, 1H, J = 7.8 Hz,
CONH), 5.05 (d, J = 9.0 Hz, 1H, CONH), 4.54 (m, 1H, 4-H), 4.17-4.22 (m, 2H, 3a-H, 2-H),
4.07-4.09 (dd, J = 10.8, 3.6 Hz, 1H, 3b-H), 3.81 (s, 3H, 8-H), 3.04-3.07 (dd, J = 13.8, 6.0 Hz, 1H,

1a-H), 2.90-2.97 (m, 2H, 5a-H, 1b-H), 2.77-2.80 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.9 (R)-(S)-2-Benzamido-3-phenylpropyl
2-(4-trifluoromethylphenylsulfonamido)-3-phenyl propanoate (3a)
mp: 168-169 ºC; yield: 48.9 %; [] 2D0 -26.1 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C32H29F3N2O5SNa, Calcd. 633.1647 [M+Na]+, found: 633.1647; H NMR (600 MHz, CDCl3): 
7.75 (d, J = 7.8 Hz, 2H, ArH), 7.69 (d, J = 7.8 Hz, 2H, ArH), 7.59 (d, J = 7.8 Hz, 2H, ArH),
7.41-7.52 (m, 3H, ArH), 7.22-7.34 (m, 5H, ArH), 7.13-7.16 (m, 3H, ArH), 6.99 (d, J = 6.6 Hz, 2H,
ArH), 6.52 (d, 1H, J = 8.4 Hz, CONH), 5.30 (d, J = 8.4 Hz, 1H, CONH), 4.64 (m, 1H, 4-H),
4.35-4.38 (dd, J = 11.4, 3.0 Hz, 1H, 3a-H), 4.11-4.15 (m, 1H, 2-H), 4.05-4.07 (dd, J = 10.8, 4.2 Hz,
1H, 3b-H), 3.09-3.12 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.99-3.02 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H),
2.86-2.93 (m, 2H, 1b-H, 5b-H). 13C NMR (150 MHz, CDCl3):  171.1, 167.1, 143.0, 136.7, 134.9,
134.3, 133.9, 131.6, 129.1×2, 129.1×2, 128.7×2, 128.7×2, 128.5×2, 127.4, 127.3×2, 127.0×2,
126.9, 126.0, 123,.9, 122.1, 66.3, 57.3, 50.0, 38.6, 37.1.
4.3.10 (R)-(R)-2-Benzamido-3-phenylpropyl
2-(4-trifluoromethylphenylsulfonamido)-3-phenyl propanoate (3b)
1
mp: 165-168 ºC; yield: 51.3 %; []2D0 52.4 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.74 (d, J = 7.2 Hz, 2H, ArH), 7.67 (d, J = 7.8 Hz, 2H, ArH), 7.58 (d, J = 7.8 Hz, 2H,
ArH), 7.41-7.52 (m, 3H, ArH), 7.22-7.34 (m, 5H, ArH), 7.14-7.18 (m, 3H, ArH), 7.01 (d, J = 6.6
Hz, 2H, ArH), 6.46 (d, 1H, J = 8.4 Hz, CONH), 5.31 (d, J = 7.8 Hz, 1H, CONH), 4.62 (m, 1H,
4-H), 4.29-4.30 (m, 1H, 3a-H), 4.19-4.23 (m, 1H, 2-H), 4.14 -4.17 (dd, J = 10.8, 4.8 Hz, 1H,
3b-H), 3.11-3.14 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.96-3.00 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H),
2.85-2.90 (m, 2H, 1b-H, 5b-H).
4.3.11 (S)-(R)-2-Benzamido-3-phenylpropyl
2-(4-trifluoromethylphenylsulfonamido)-3-phenyl propanoate (3c)
1
mp: 168-170 ºC; yield: 50.6 %; []2D0 26.7 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.75 (d, J = 7.8 Hz, 2H, ArH), 7.69 (d, J = 7.8 Hz, 2H, ArH), 7.59 (d, J = 7.8 Hz, 2H,
ArH), 7.41-7.52 (m, 3H, ArH), 7.22-7.34 (m, 5H, ArH), 7.13-7.16 (m, 3H, ArH), 6.99 (d, J = 6.6
Hz, 2H, ArH), 6.52 (d, 1H, J = 8.4 Hz, CONH), 5.30 (d, J = 8.4 Hz, 1H, CONH), 4.64 (m, 1H,
4-H), 4.35-4.38 (dd, J = 11.4, 3.0 Hz, 1H, 3a-H), 4.11-4.15 (m, 1H, 2-H), 4.05-4.07 (dd, J = 10.8,
4.2 Hz, 1H, 3b-H), 3.09-3.12 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.99-3.02 (dd, J = 13.8, 6.6 Hz, 1H,

5a-H), 2.86-2.93 (m, 2H, 1b-H, 5b-H)
4.3.12 (S)-(S)-2-Benzamido-3-phenylpropyl
2-(4-trifluoromethylphenylsulfonamido)-3-phenyl propanoate (3d)
1
mp: 163-166 ºC; yield: 59.9 %; []2D0 -51.9 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.74 (d, J = 7.2 Hz, 2H, ArH), 7.67 (d, J = 7.8 Hz, 2H, ArH), 7.58 (d, J = 7.8 Hz, 2H,
ArH), 7.41-7.52 (m, 3H, ArH), 7.22-7.34 (m, 5H, ArH), 7.14-7.18 (m, 3H, ArH), 7.01 (d, J = 6.6
Hz, 2H, ArH), 6.46 (d, 1H, J = 8.4 Hz, CONH), 5.31 (d, J = 7.8 Hz, 1H, CONH), 4.62 (m, 1H,
4-H), 4.29-4.30 (m, 1H, 3a-H), 4.19-4.23 (m, 1H, 2-H), 4.14 -4.17 (dd, J = 10.8, 4.8 Hz, 1H,
3b-H), 3.11-3.14 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.96-3.00 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H),
2.85-2.90 (m, 2H, 1b-H, 5b-H).
4.3.13
(R)-(S)-2-Benzamido-3-phenylpropyl
2-(4-fluorophenylsulfonamido)-3-phenyl
propanoate (4a)
mp: 171-172 ºC; yield: 45.7%; [] 20 -32.9 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
D
1
C31H29FN2O5SNa, Calcd. 583.1679 [M+Na]+, found: 583.1680; H NMR (600 MHz, CDCl3): 
7.75 (d, J = 7.2 Hz, 2H, Ar), 7.60-7.62 (m, 2H, ArH), 7.41-7.51 (m, 3H, ArH), 7.18-7.33 (m, 8H,
ArH), 7.00-7.03 (m, 4H, ArH), 6.52 (d, 1H, J 8.4 Hz, CONH), 5.14 (d, J = 9.0 Hz, 1H, CONH),
4.61 (m, 1H, 4-H), 4.34-4.36 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.10-4.13 (m, 1H, 2-H), 4.02-4.05
(dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.06-3.09 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.97-3.01 (dd, J =
13.8, 6.6 Hz, 1H, 5a-H), 2.91-2.95 (dd, J = 13.8, 8.4 Hz, 1H, 1b-H), 2.87-2.90 (dd, J = 13.8, 7.8
Hz, 1H, 5b-H); 13C NMR (150 MHz, CDCl3)  171.3, 167.1, 165.8, 164.1, 136.8, 135.4, 134.9,
133.9, 131.6, 129.7, 129.6, 129.1×3, 128.7×2, 128.7×2, 128.5×2, 127.3, 127.0×2, 126.9, 116.2,
116.1, 66.1, 57.1, 50.1, 38.7, 37.1.
4.3.14
(R)-(R)-2-Benzamido-3-phenylpropyl
2-(4-fluorophenylsulfonamido)-3-phenyl
propanoate (4b)
1
mp: 167-169 ºC; yield: 45.9% ; []2D0 65.8 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.74 (d, J = 7.8 Hz, 2H, ArH), 7.59-7.61 (m, 2H, ArH), 7.41-7.52 (m, 3H, ArH),
7.19-7.33 (m, 8H, ArH), 6.99-7.04 (m, 4H, ArH), 6.49 (d, 1H, J 7.8 Hz, CONH), 5.19 (d, J = 9.0
Hz, 1H, CONH), 4.58 (m, 1H, 4-H), 4.24-4.26 (dd, J = 10.8, 3.0 Hz, 1H, 3a-H), 4.17-4.20 (m, 1H,
2-H), 4.11-4.14 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.08-3.11 (dd, J = 14.4, 6.0 Hz, 1H, 1a-H),
2.94-2.97 (dd, J = 13.8, 7.2 Hz, 1H, 5a-H), 2.89-2.93 (dd, J = 13.8, 7.8 Hz, 1H, 1b-H), 2.82-2.86

(dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.15
(S)-(R)-2-Benzamido-3-phenylpropyl
2-(4-fluorophenylsulfonamido)-3-phenyl
propanoate (4c)
1
mp: 171-172 ºC; yield: 54.5% ; []2D0 33.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.75 (d, J = 7.2 Hz, 2H, Ar), 7.60-7.62 (m, 2H, ArH), 7.41-7.51 (m, 3H, ArH),
7.18-7.33 (m, 8H, ArH), 7.00-7.03 (m, 4H, ArH), 6.52 (d, 1H, J = 8.4 Hz, CONH), 5.14 (d, J = 9.0
Hz, 1H, CONH), 4.61 (m, 1H, 4-H), 4.34-4.36 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.10-4.13 (m, 1H,
2-H), 4.02-4.05 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.06-3.09 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H),
2.97-3.01 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.91-2.95 (dd, J = 13.8, 8.4 Hz, 1H, 1b-H), 2.87-2.90
(dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.16
(S)-(S)-2-Benzamido-3-phenylpropyl
2-(4-fluorophenylsulfonamido)-3-phenyl
propanoate (4d)
mp: 166-169 ºC; yield: 60.1 % ; []2D0 -66.3 (c 0.4 CHCl3/MeOH=1:1，v/v); 1H NMR (600 MHz,
CDCl3):  7.74 (d, J = 7.8 Hz, 2H, ArH), 7.59-7.61 (m, 2H, ArH), 7.41-7.52 (m, 3H, ArH),
7.19-7.33 (m, 8H, ArH), 6.99-7.04 (m, 4H, ArH), 6.49 (d, 1H, J = 7.8 Hz, CONH), 5.19 (d, J = 9.0
Hz, 1H, CONH), 4.58 (m, 1H, 4-H), 4.24-4.26 (dd, J = 10.8, 3.0 Hz, 1H, 3a-H), 4.17-4.20 (m, 1H,
2-H), 4.11-4.14 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.08-3.11 (dd, J = 14.4, 6.0 Hz, 1H, 1a-H),
2.94-2.97 (dd, J = 13.8, 7.2 Hz, 1H, 5a-H), 2.89-2.93 (dd, J = 13.8, 7.8 Hz, 1H, 1b-H), 2.82-2.86
(dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.17 (R)-(S)-2-Benzamido-3-phenylpropyl 2-(phenylsulfonamido)-3-phenyl propanoate (5a)
mp: 173-175 ºC; yield: 66.3 % ; [] 2D0 -31.3 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C31H30N2O5SNa, Calcd. 565.1773 [M+Na]+, found: 565.1774; H NMR (600 MHz, CDCl3): 
7.75 (d, J = 7.8 Hz, 2H, ArH), 7.65 (d, J = 7.8 Hz, 2H, ArH), 7.48-7.52 (m, 2H, ArH), 7.17-7.43
(m, 12H, ArH), 7.02-7.03 (m, 2H, ArH), 6.54 (d, 1H, J = 8.4 Hz, CONH), 5.15 (d, J = 9.0 Hz, 1H,
CONH), 4.56 (m, 1H, 4-H), 4.28-4.29 (dd, J = 11.4, 4.8 Hz, 1H, 3a-H), 4.13-4.17 (m, 1H, 2-H),
3.97-3.99 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.04-3.07 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 2.94-2.99
(m, 2H, 5a-H, 1b-H), 2.82-2.86 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H); 13C NMR (150 MHz, CDCl3): 
170.8, 167.1, 139.1, 137.0, 134.8, 134.0, 132.9, 131.5, 129.2×2, 129.0×2, 129.0×2, 128.7×2,
128.6×2, 128.4×2, 127.4, 127.1×2, 126.9×2, 126.8, 65.9, 57.1, 49.9, 38.8, 37.2.
4.3.18 (R)-(R)-2-Benzamido-3-phenylpropyl 2-(phenylsulfonamido)-3-phenyl propanoate

(5b)
1
mp: 168-169 ºC; yield: 69.2 %; []2D0 62.4 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.74 (d, J = 7.2 Hz, 2H, ArH), 7.66 (d, J = 8.4 Hz, 2H, ArH), 7.41-7.51 (m, 4H, ArH),
7.18-7.36 (m, 10H, ArH), 7.03-7.05 (m, 2H, ArH), 6.46 (d, 1H, J = 8.4 Hz, CONH), 5.16 (d, J =
9.0 Hz, 1H, CONH), 4.53 (m, 1H, 4-H), 4.21-4.24 (m, 1H, 2-H), 4.16-4.18 (dd, J = 11.4, 3.6 Hz,
1H, 3a-H), 4.05-4.08 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.05-3.08 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H),
2.91-2.98 (m, 2H, 5a-H, 1b-H), 2.76-2.80 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.19 (S)-(R)-2-Benzamido-3-phenylpropyl 2-(phenylsulfonamido)-3-phenyl propanoate (5c)
1
mp: 170-171 ºC; yield: 70.1 %; []2D0 31.0 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.75 (d, J = 7.8 Hz, 2H, ArH), 7.65 (d, J = 7.8 Hz, 2H, ArH), 7.48-7.52 (m, 2H, ArH),
7.17-7.43 (m, 12H, ArH), 7.02-7.03 (m, 2H, ArH), 6.54 (d, 1H, J = 8.4 Hz, CONH), 5.15 (d, J =
9.0 Hz, 1H, CONH), 4.56 (m, 1H, 4-H), 4.28-4.29 (dd, J = 11.4, 4.8 Hz, 1H, 3a-H), 4.13-4.17 (m,
1H, 2-H), 3.97-3.99 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.04-3.07 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H),
2.94-2.99 (m, 2H, 5a-H, 1b-H), 2.82-2.86 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.20 (S)-(S)-2-Benzamido-3-phenylpropyl 2-(phenylsulfonamido)-3-phenyl propanoate (5d)
1
mp: 168-170 ºC; yield: 68.7 %; []2D0 -61.8 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.74 (d, J = 7.2 Hz, 2H, ArH), 7.66 (d, J = 8.4 Hz, 2H, ArH), 7.41-7.51 (m, 4H, ArH),
7.18-7.36 (m, 10H, ArH), 7.03-7.05 (m, 2H, ArH), 6.46 (d, 1H, J = 8.4 Hz, CONH), 5.16 (d, J =
9.0 Hz, 1H, CONH), 4.53 (m, 1H, 4-H), 4.21-4.24 (m, 1H, 2-H), 4.16-4.18 (dd, J = 11.4, 3.6 Hz,
1H, 3a-H), 4.05-4.08 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.05-3.08 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H),
2.91-2.98 (m, 2H, 5a-H, 1b-H), 2.76-2.80 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.21
(R)-(S)-2-Benzamido-3-phenylpropyl
2-(3-bromophenylsulfonamido)-3-phenyl
propanoate (6a)
mp: 160-161 ºC; yield: 50.7 %; [] 2D0 -15.2 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C31H29BrN2O5SNa, Calcd. 643.0878 [M+Na]+, found: 643.0878; H NMR (600 MHz, CDCl3): 
7.78-7.79 (m, 1H, ArH), 7.73 (d, J = 7.2 Hz, 2H, ArH), 7.49-7.60 (m, 3H, ArH), 7.41-7.44 (m, 2H,
ArH), 7.31-7.34 (m, 2H, ArH), 7.19-7.26 (m, 7H, ArH), 7.03-7.04 (m, 2H, ArH), 6.43 (d, 1H, J =
8.4 Hz, CONH), 5.20 (d, J = 9.0 Hz, 1H, CONH), 4.58 (m, 1H, 4-H), 4.21-4.26 (m, 2H, 3a-H,
2-H), 4.12-4.14 (dd, J = 11.4, 5.4 Hz, 1H, 3b-H), 3.09-3.12 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H),
2.91-2.98 (m, 2H, 5a-H, 1b-H), 2.83-2.86 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H); 13C NMR (150 MHz,

CDCl3)  170.6, 167.2, 141.1, 136.9, 135.8, 134.7, 134.0, 131.6, 130.4, 129.8, 129.2×2, 129.0×2,
128.7×2, 128.7×2, 128.5×2, 127.5, 127.0×2, 126.8, 125.4, 122.9, 66.2, 57.3, 49.8, 38.7, 37.2.
4.3.22
(R)-(R)-2-Benzamido-3-phenylpropyl
2-(3-bromophenylsulfonamido)-3-phenyl
propanoate (6b)
1
mp: 157-158 ºC; yield: 52.7% ; []2D0 31.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.81-7.79 (m, 1H, ArH), 7.74 (d, J = 7.2 Hz, 2H, ArH), 7.49-7.64 (m, 3H, ArH),
7.41-7.44 (m, 2H, ArH), 7.31-7.33 (m, 2H, ArH), 7.17-7.26 (m, 7H, ArH), 7.01-7.02 (m, 2H,
ArH), 6.48 (d, 1H, J = 8.4 Hz, CONH), 5.19 (d, J = 9.0 Hz, 1H, CONH), 4.61 (m, 1H, 4-H),
4.33-4.35 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.14-4.18 (m, 1H, 2-H), 4.03 -4.06 (dd, J = 11.4, 4.8
Hz, 1H, 3b-H), 3.06-3.10 (dd, J = 14.4, 6.0 Hz, 1H, 1a-H), 2.96-3.00 (dd, J = 13.8, 7.2 Hz, 1H,
5a-H), 2.91-2.95 (dd, J = 14.4, 8.4 Hz, 1H, 1b-H), 2.87-2.90 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.23
(S)-(R)-2-Benzamido-3-phenylpropyl
2-(3-bromophenylsulfonamido)-3-phenyl
propanoate (6c)
1
mp: 160-162 ºC; yield: 53.3 %; []2D0 15.8 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.78-7.79 (m, 1H, ArH), 7.73 (d, J = 7.2 Hz, 2H, ArH), 7.49-7.60 (m, 3H, ArH),
7.41-7.44 (m, 2H, ArH), 7.31-7.34 (m, 2H, ArH), 7.19-7.26 (m, 7H, ArH), 7.03-7.04 (m, 2H,
ArH), 6.43 (d, 1H, J = 8.4 Hz, CONH), 5.20 (d, J = 9.0 Hz, 1H, CONH), 4.58 (m, 1H, 4-H),
4.21-4.26 (m, 2H, 3a-H, 2-H), 4.12-4.14 (dd, J = 11.4, 5.4 Hz, 1H, 3b-H), 3.09-3.12 (dd, J = 13.8,
6.0 Hz, 1H, 1a-H), 2.91-2.98 (m, 2H, 5a-H, 1b-H), 2.83-2.86 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.24
(S)-(S)-2-Benzamido-3-phenylpropyl
2-(3-bromophenylsulfonamido)-3-phenyl
propanoate (6d)
mp: 157-158 ºC; yield: 56.1 %; []2D0 -32.1 (c 0.4 CHCl3/MeOH=1:1，v/v); 1H NMR (600 MHz,
CDCl3):  7.81-7.79 (m, 1H, ArH), 7.74 (d, J = 7.2 Hz, 2H, ArH), 7.49-7.64 (m, 3H, ArH),
7.41-7.44 (m, 2H, ArH), 7.31-7.33 (m, 2H, ArH), 7.17-7.26 (m, 7H, ArH), 7.01-7.02 (m, 2H,
ArH), 6.48 (d, 1H, J = 8.4 Hz, CONH), 5.19 (d, J = 9.0 Hz, 1H, CONH), 4.61 (m, 1H, 4-H),
4.33-4.35 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.14-4.18 (m, 1H, 2-H), 4.03 -4.06 (dd, J = 11.4, 4.8
Hz, 1H, 3b-H), 3.06-3.10 (dd, J = 14.4, 6.0 Hz, 1H, 1a-H), 2.96-3.00 (dd, J = 13.8, 7.2 Hz, 1H,
5a-H), 2.91-2.95 (dd, J = 14.4, 8.4 Hz, 1H, 1b-H), 2.87-2.90 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.25
(R)-(S)-2-Benzamido-3-phenylpropyl
2-(2-bromophenylsulfonamido)-3-phenyl
propanoate (7a)

mp: 157-158 ºC; yield: 46.8 %; [] 2D0 -15.9 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C31H29BrN2O5SNa, Calcd. 643.0878 [M+Na]+, found: 643.0878; H NMR (600 MHz, CDCl3): 
7.95-7.97 (m, 1H, ArH), 7.74 (d, J = 8.4 Hz, 2H, ArH), 7.61-7.62 (m, 1H, ArH), 7.49-7.52 (m, 1H,
ArH), 7.23-7.44 (m, 7H, ArH), 7.16-7.20 (m, 5H, ArH), 7.06-7.08 (m, 2H, ArH), 6.50 (d, 1H, J =
8.4 Hz, CONH), 5.55 (d, J = 8.4 Hz, 1H, CONH), 4.57 (m, 1H, 4-H), 4.28-4.31 (dd, J = 11.4, 3.0
Hz, 1H, 3a-H), 4.20-4.23 (m, 1H, 2-H), 3.98-4.00 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.04-3.11 (m,
2H, 1-H), 2.94-2.97 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.80-2.84 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H);
13C NMR (150 MHz, CDCl3):  170.6, 167.0, 138.4, 137.0, 135.2, 134.6, 134.1, 133.8, 131.5,
130.8, 129.2×2, 129.0×2, 128.8×2, 128.6×2, 128.4×2, 127.5, 127.5, 127.1×2, 126.7, 120.1, 65.8,
57.5, 49.9, 38.6, 37.2.
4.3.26
(R)-(R)-2-Benzamido-3-phenylpropyl
2-(2-bromophenylsulfonamido)-3-phenyl
propanoate (7b)
1
mp: 151-153 ºC; yield: 45.6 %; []2D0 31.9 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.97-7.98 (m, 1H, ArH), 7.72 (d, J = 7.2 Hz, 2H, ArH), 7.60-7.62 (m, 1H, ArH),
7.50-7.52 (m, 1H, ArH), 7.42-7.45 (m, 2H, ArH), 7.23-7.34 (m, 5H, ArH), 7.14-7.19 (m, 5H,
ArH), 7.07-7.08 (m, 2H, ArH), 6.41 (d, 1H, J = 7.8 Hz, CONH), 5.59 (d, J = 8.4 Hz, 1H, CONH),
4.52 (m, 1H, 4-H), 4.30-4.33 (m, 1H, 2-H), 4.10-4.11 (d, J = 4.0 Hz, 1H, 3-H), 3.08-3.12 (dd, J =
13.8, 6.6 Hz, 1H, 1a-H), 3.03-3.06 (dd, J = 13.8, 6.6 Hz, 1H, 1b-H), 2.88-2.92 (dd, J = 13.8, 6.6
Hz, 1H, 5a-H), 2.72-2.76 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.27
(S)-(R)-2-Benzamido-3-phenylpropyl
2-(2-bromophenylsulfonamido)-3-phenyl
propanoate (7c)
1
mp: 156-158 ºC; yield: 47.8 %; []2D0 16.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.95-7.97 (m, 1H, ArH), 7.74 (d, J = 8.4 Hz, 2H, ArH), 7.61-7.62 (m, 1H, ArH),
7.49-7.52 (m, 1H, ArH), 7.23-7.44 (m, 7H, ArH), 7.16-7.20 (m, 5H, ArH), 7.06-7.08 (m, 2H,
ArH), 6.50 (d, 1H, J = 8.4 Hz, CONH), 5.55 (d, J = 8.4 Hz, 1H, CONH), 4.57 (m, 1H, 4-H),
4.28-4.31 (dd, J = 11.4, 3.0 Hz, 1H, 3a-H), 4.20-4.23 (m, 1H, 2-H), 3.98-4.00 (dd, J = 11.4, 4.2 Hz,
1H, 3b-H), 3.04-3.11 (m, 2H, 1-H), 2.94-2.97 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.80-2.84 (dd, J =
13.8, 7.8 Hz, 1H, 5b-H).
4.3.28
(S)-(S)-2-Benzamido-3-phenylpropyl
2-(2-bromophenylsulfonamido)-3-phenyl
propanoate (7d)

1
mp: 151-152 ºC; yield: 45.5 %; []2D0 -32.3 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.97-7.98 (m, 1H, ArH), 7.72 (d, J = 7.2 Hz, 2H, ArH), 7.60-7.62 (m, 1H, ArH),
7.50-7.52 (m, 1H, ArH), 7.42-7.45 (m, 2H, ArH), 7.23-7.34 (m, 5H, ArH), 7.14-7.19 (m, 5H,
ArH), 7.07-7.08 (m, 2H, ArH), 6.41 (d, 1H, J = 7.8 Hz, CONH), 5.59 (d, J = 8.4 Hz, 1H, CONH),
4.52 (m, 1H, 4-H), 4.30-4.33 (m, 1H, 2-H), 4.10-4.11 (d, J = 4.0 Hz, 1H, 3-H), 3.08-3.12 (dd, J =
13.8, 6.6 Hz, 1H, 1a-H), 3.03-3.06 (dd, J = 13.8, 6.6 Hz, 1H, 1b-H), 2.88-2.92 (dd, J = 13.8, 6.6
Hz, 1H, 5a-H), 2.72-2.76 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.29 (R)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 4-difluorophenylsulfonamido)-3-phenyl
propanoate (8a)
mp: 165-166 ºC; yield: 50.9 %; [] 2D0 -21.3 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C31H28F2N2O5SNa, Calcd. 601.1585 [M+Na]+, found: 601.1585; H NMR (600 MHz, CDCl3): 
7.71-7.75 (m, 3H, ArH), 7.50-7.52 (m, 1H, ArH), 7.42-7.44 (m, 2H, ArH), 7.25-7.34 (m, 3H,
ArH), 7.18-7.22 (m, 5H, ArH), 7.06-7.07 (m, 2H, ArH), 6.87-6.90 (m, 1H, ArH), 6.72-6.76 (m,
1H, ArH), 6.45 (d, 1H, J = 8.4 Hz, CONH), 5.34 (d, J = 8.4 Hz, 1H, CONH), 4.62 (m, 1H, 4-H),
4.31-4.34 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.27-4.31 (m, 1H, 2-H), 4.07-4.10 (dd, J = 11.4, 4.2 Hz,
1H, 3b-H), 3.10-3.13 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.97-3.03 (m, 2H, 5a-H, 1b-H), 2.86-2.89
(dd, J = 13.8, 7.8 Hz, 1H, 5b-H); 13C NMR (150 MHz, CDCl3):  170.7, 167.1, 165.8, 159.4,
136.9, 134.8, 134.0, 131.5, 131.3, 129.2×2, 129.0×2, 128.7×2, 128.7×2, 128.4×2, 127.4,
127.0×2, 126.8, 124.2, 111.5, 106.6, 66.0, 57.4, 49.8, 38.7, 37.2.
4.3.30 (R)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 4-difluorophenylsulfonamido)-3-phenyl
propanoate (8b)
1
mp: 160-162 ºC; yield: 54.6% ; []2D0 42.3 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.71-7.76 (m, 3H, ArH), 7.50-7.52 (m, 1H, ArH), 7.42-7.44 (m, 2H, ArH), 7.16-7.33 (m,
8H, ArH), 7.07-7.08 (m, 2H, ArH), 6.84-6.87 (m, 1H, ArH), 6.73-6.76 (m, 1H, ArH), 6.41 (d, 1H,
J = 8.4 Hz, CONH), 5.42 (d, J = 9.0 Hz, 1H, CONH), 4.58 (m, 1H, 4-H), 4.35-4.38 (m, 1H, 2-H),
4.21-4.24 (dd, J = 11.4, 4.2 Hz, 1H, 3a-H), 4.13-4.16 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.11-3.14
(dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 2.99-3.02 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H), 2.93-2.97 (dd, J =
13.8, 6.6 Hz, 1H, 5a-H), 2.82-2.85 (dd, J = 14.4, 7.8 Hz, 1H, 5b-H).
4.3.31 (S)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 4-difluorophenylsulfonamido)-3-phenyl
propanoate (8c)

1
mp: 166-168 ºC; yield: 56.7 %; []2D0 20.9 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.71-7.75 (m, 3H, ArH), 7.50-7.52 (m, 1H, ArH), 7.42-7.44 (m, 2H, ArH), 7.25-7.34 (m,
3H, ArH), 7.18-7.22 (m, 5H, ArH), 7.06-7.07 (m, 2H, ArH), 6.87-6.90 (m, 1H, ArH), 6.72-6.76
(m, 1H, ArH), 6.45 (d, 1H, J = 8.4 Hz, CONH), 5.34 (d, J = 8.4 Hz, 1H, CONH), 4.62 (m, 1H,
4-H), 4.31-4.34 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.27-4.31 (m, 1H, 2-H), 4.07-4.10 (dd, J = 11.4,
4.2 Hz, 1H, 3b-H), 3.10-3.13 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H), 2.97-3.03 (m, 2H, 5a-H, 1b-H),
2.86-2.89 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.32 (S)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 4-difluorophenylsulfonamido)-3-phenyl
propanoate (8d)
mp: 161-162 ºC; yield: 54.4% ; []2D0 -41.9 (c 0.4 CHCl3/MeOH=1:1，v/v); 1H NMR (600 MHz,
CDCl3):  7.71-7.76 (m, 3H, ArH), 7.50-7.52 (m, 1H, ArH), 7.42-7.44 (m, 2H, ArH), 7.16-7.33 (m,
8H, ArH), 7.07-7.08 (m, 2H, ArH), 6.84-6.87 (m, 1H, ArH), 6.73-6.76 (m, 1H, ArH), 6.41 (d, 1H,
J = 8.4 Hz, CONH), 5.42 (d, J = 9.0 Hz, 1H, CONH), 4.58 (m, 1H, 4-H), 4.35-4.38 (m, 1H, 2-H),
4.21-4.24 (dd, J = 11.4, 4.2 Hz, 1H, 3a-H), 4.13-4.16 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.11-3.14
(dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 2.99-3.02 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H), 2.93-2.97 (dd, J =
13.8, 6.6 Hz, 1H, 5a-H), 2.82-2.85 (dd, J = 14.4, 7.8 Hz, 1H, 5b-H).
4.3.33 (R)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 6-difluorophenylsulfonamido)-3-phenyl
propanoate (9a)
mp: 154-155 ºC; yield: 45.1 %; [] 2D0 -24.1 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C31H28F2N2O5SNa, Calcd. 601.1585 [M+Na]+, found: 601.1586; H NMR (600 MHz, CDCl3): 
7.75 (d, J = 7.2 Hz, 2H, ArH), 7.48-7.51 (m, 1H, ArH), 7.41-7.45 (m, 3H, ArH), 7.23-7.32 (m, 3H,
ArH), 7.14-7.20 (m, 5H, ArH), 7.08-7.10 (m, 2H, ArH), 6.87-6.90 (m, 2H, ArH), 6.48 (d, 1H, J =
8.4 Hz, CONH), 5.60 (d, J = 8.4 Hz, 1H, CONH), 4.59 (m, 1H, 4-H), 4.44-4.47 (m, 1H, 2-H),
4.29-4.32 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.04-4.06 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.13-3.16
(dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 3.05-3.09 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H), 2.94-2.97 (dd, J =
13.8, 5.4 Hz, 1H, 5a-H), 2.83-2.87 (dd, J = 14.4, 8.4 Hz, 1H, 5b-H); 13C NMR (150 MHz, CDCl3):
 170.5, 167.0, 160.1, 158.3, 137.0, 134.7, 134.5, 133.9, 131.5, 129.2×2, 129.0×2, 128.8×2,
128.6×2, 128.4×2, 127.4, 127.0×2, 126.8, 117.8, 113.0, 112.9, 66.0, 57.4, 49.9, 38.7, 37.1.
4.3.34 (R)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 6-difluorophenylsulfonamido)-3-phenyl
propanoate (9b)

1
mp: 150-152 ºC; yield: 43.8 %; []2D0 47.6 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.72 (d, J = 7.2 Hz, 2H, ArH), 7.49-7.52 (m, 1H, ArH), 7.37-7.44 (m, 3H, ArH),
7.15-7.32 (m, 8H, ArH), 7.10-7.11 (m, 2H, ArH), 6.84-6.87 (m, 2H, ArH), 6.39 (d, 1H, J = 8.4 Hz,
CONH), 5.56 (d, J = 9.0 Hz, 1H, CONH), 4.50-4.57 (m, 2H, 4-H, 2-H), 4.15-4.18 (dd, J = 11.4,
4.2 Hz, 1H, 3a-H), 4.08-4.11 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.13 -3.16 (dd, J = 13.8, 6.0 Hz, 1H,
1a-H), 3.06-3.09 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H), 2.89-2.92 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H),
2.76-2.79 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.35 (S)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 6-difluorophenylsulfonamido)-3-phenyl
propanoate (9c)
1
mp: 154-155 ºC; yield: 46.2 %; []2D0 22.3 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.75 (d, J = 7.2 Hz, 2H, ArH), 7.48-7.51 (m, 1H, ArH), 7.41-7.45 (m, 3H, ArH),
7.23-7.32 (m, 3H, ArH), 7.14-7.20 (m, 5H, ArH), 7.08-7.10 (m, 2H, ArH), 6.87-6.90 (m, 2H,
ArH), 6.48 (d, 1H, J = 8.4 Hz, CONH), 5.60 (d, J = 8.4 Hz, 1H, CONH), 4.59 (m, 1H, 4-H),
4.44-4.47 (m, 1H, 2-H), 4.29-4.32 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.04-4.06 (dd, J = 11.4, 4.2 Hz,
1H, 3b-H), 3.13-3.16 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 3.05-3.09 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H),
2.94-2.97 (dd, J = 13.8, 5.4 Hz, 1H, 5a-H), 2.83-2.87 (dd, J = 14.4, 8.4 Hz, 1H, 5b-H).
4.3.36 (S)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 6-difluorophenylsulfonamido)-3-phenyl
propanoate (9d)
mp: 149-152 ºC; yield: 45.5 %; []2D0 -45.7 (c 0.4 CHCl3/MeOH=1:1，v/v); 1H NMR (600 MHz,
CDCl3):  7.72 (d, J = 7.2 Hz, 2H, ArH), 7.49-7.52 (m, 1H, ArH), 7.37-7.44 (m, 3H, ArH),
7.15-7.32 (m, 8H, ArH), 7.10-7.11 (m, 2H, ArH), 6.84-6.87 (m, 2H, ArH), 6.39 (d, 1H, J = 8.4 Hz,
CONH), 5.56 (d, J = 9.0 Hz, 1H, CONH), 4.50-4.57 (m, 2H, 4-H, 2-H), 4.15-4.18 (dd, J = 11.4,
4.2 Hz, 1H, 3a-H), 4.08-4.11 (dd, J = 11.4, 4.8 Hz, 1H, 3b-H), 3.13 -3.16 (dd, J = 13.8, 6.0 Hz, 1H,
1a-H), 3.06-3.09 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H), 2.89-2.92 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H),
2.76-2.79 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.37 (R)-(S)-2-Benzamido-3-phenylpropyl 2-(5-bromo-2-methoxy
phenylsulfonamido)-3-phenyl propanoate (10a)
mp: 148-150 ºC; yield: 47.8 %; [] 2D0 -34.9 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C32H31BrN2O6SNa, Calcd. 673.0984 [M+Na]+, found: 673.0985; H NMR (600 MHz, CDCl3): 
7.92 (d, J = 2.4 Hz, 1H, ArH), 7.72 (d, J = 8.4 Hz, 2H, ArH), 7.57-7.59 (dd, J = 2.4 Hz, 9.0 Hz, 1H,

ArH), 7.50-7.53 (m, 1H, ArH), 7.43-7.45 (m, 2H, ArH), 7.16-7.33 (m, 8H, ArH), 7.08-7.09 (m,
2H, ArH), 6.77 (d, J = 8.4 Hz, 1H, ArH), 6.44 (d, 1H, J = 8.4 Hz, CONH), 5.46 (d, J = 6.6 Hz, 1H,
CONH), 4.52 (m, 1H, 4-H), 4.29-4.32 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.21-4.25 (dd, J = 13.8,
7.2 Hz, 1H, 2-H), 3.94-3.96 (dd, J = 10.8, 3.6 Hz, 1H, 3b-H), 3.73 (s, 3H, 8-H), 3.09-3.12 (dd, J =
13.8, 6.0 Hz, 1H, 1a-H), 3.03-3.07 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H), 2.91-2.95 (dd, J = 13.8, 6.6
Hz, 1H, 5a-H), 2.81-2.84 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H); 13C NMR (150 MHz, CDCl3)  170.9,
167.1, 155.2, 137.3, 137.0, 134.9, 134.1, 132.1, 131.5, 129.2×2, 129.0×2, 128.7×2, 128.6×2,
128.4×2, 128.4, 127.4, 127.0×2, 126.7, 113.8, 112.3, 65.7, 57.4, 56.4, 49.9, 38.9, 37.1.
4.3.38 (R)-(R)-2-Benzamido-3-phenylpropyl 2-(5-bromo-2-methoxy
phenylsulfonamido)-3-phenyl propanoate (10b)
1
mp: 145-146 ºC; yield: 42.2 %; []2D0 69.1 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.94 (d, J = 2.4 Hz, 1H, ArH), 7.69 (d, J = 7.8 Hz, 2H, ArH), 7.50-7.52 (m, 2H, ArH),
7.42-7.45 (m, 2H, ArH), 7.17-7.33 (m, 8H, ArH), 7.09-7.10 (m, 2H, ArH), 6.75 (d, J = 9.0 Hz, 1H,
ArH), 6.33 (d, 1H, J = 8.4 Hz, CONH), 5.50 (d, J = 7.8 Hz, 1H, CONH), 4.50 (m, 1H, 4-H),
4.28-4.31 (dd, J = 13.8, 6.6 Hz, 1H, 2-H), 4.08-4.15 (m, 2H, 3-H), 3.76 (s, 3H, 8-H), 3.09-3.12 (dd,
J = 13.8, 6.6 Hz, 1H, 1a-H), 3.03-3.07 (dd, J = 13.8, 6.6 Hz, 1H, 1b-H), 2.89-2.92 (dd, J = 13.8,
6.6 Hz, 1H, 5a-H), 2.75-2.78 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.39 (S)-(R)-2-Benzamido-3-phenylpropyl 2-(5-bromo-2-methoxy
phenylsulfonamido)-3-phenyl propanoate (10c)
1
mp: 148-151 ºC; yield: 47.6 %; []2D0 34.6 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.92 (d, J = 2.4 Hz, 1H, ArH), 7.72 (d, J = 8.4 Hz, 2H, ArH), 7.57-7.59 (dd, J = 2.4 Hz,
9.0 Hz, 1H, ArH), 7.50-7.53 (m, 1H, ArH), 7.43-7.45 (m, 2H, ArH), 7.16-7.33 (m, 8H, ArH),
7.08-7.09 (m, 2H, ArH), 6.77 (d, J = 8.4 Hz, 1H, ArH), 6.44 (d, 1H, J = 8.4 Hz, CONH), 5.46 (d, J
= 6.6 Hz, 1H, CONH), 4.52 (m, 1H, 4-H), 4.29-4.32 (dd, J = 11.4, 3.6 Hz, 1H, 3a-H), 4.21-4.25
(dd, J = 13.8, 7.2 Hz, 1H, 2-H), 3.94-3.96 (dd, J = 10.8, 3.6 Hz, 1H, 3b-H), 3.73 (s, 3H, 8-H),
3.09-3.12 (dd, J = 13.8, 6.0 Hz, 1H, 1a-H), 3.03-3.07 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H), 2.91-2.95
(dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.81-2.84 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.40 (S)-(S)-2-Benzamido-3-phenylpropyl 2-(5-bromo-2-methoxy
phenylsulfonamido)-3-phenyl propanoate (10d)
1
mp: 144-145 ºC; yield: 43.4 %; []2D0 -70.5 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,

CDCl3):  7.94 (d, J = 2.4 Hz, 1H, ArH), 7.69 (d, J = 7.8 Hz, 2H, ArH), 7.50-7.52 (m, 2H, ArH),
7.42-7.45 (m, 2H, ArH), 7.17-7.33 (m, 8H, ArH), 7.09-7.10 (m, 2H, ArH), 6.75 (d, J = 9.0 Hz, 1H,
ArH), 6.33 (d, 1H, J = 8.4 Hz, CONH), 5.50 (d, J = 7.8 Hz, 1H, CONH), 4.50 (m, 1H, 4-H),
4.28-4.31 (dd, J = 13.8, 6.6 Hz, 1H, 2-H), 4.08-4.15 (m, 2H, 3-H), 3.76 (s, 3H, 8-H), 3.09-3.12 (dd,
J = 13.8, 6.6 Hz, 1H, 1a-H), 3.03-3.07 (dd, J = 13.8, 6.6 Hz, 1H, 1b-H), 2.89-2.92 (dd, J = 13.8,
6.6 Hz, 1H, 5a-H), 2.75-2.78 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.41 (R)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 5-dimethoxyphenylsulfonamido)-3-phenyl
propanoate (11a)
mp: 151-152 ºC; yield: 67.7 %; [] 2D0 -36.5 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C33H34N2O7SNa, Calcd. 625.1984 [M+Na]+, found: 625.1985; H NMR (600 MHz, CDCl3): 
7.72 (d, J = 7.2 Hz, 2H, ArH), 7.47-7.49 (m, 1H, ArH), 7.40-7.42 (m, 2H, ArH), 7.14-7.34 (m, 9H,
ArH), 7.07-7.08 (m, 2H, ArH), 7.00-7.02 (dd, J = 3.6 Hz, 9.0 Hz, 1H, ArH), 6.81 (d, J = 9.0 Hz,
1H, ArH), 6.49 (d, 1H, J = 8.4 Hz, CONH), 5.49 (d, J = 6.6 Hz, 1H, CONH), 4.50 (m, 1H, 4-H),
4.25-4.28 (dd, J = 11.4, 3.0 Hz, 1H, 3a-H), 4.18-4.21 (dd, J = 13.8, 6.6 Hz, 1H, 2-H), 3.89-3.91
(dd, J = 11.4, 3.6 Hz, 1H, 3b-H), 3.74 (s, 3H, -OCH3), 3.68 (s, 3H, -OCH3), 3.06-3.08 (m, 2H,
1-H), 2.89-2.92 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.76-2.79 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H); 13
C
NMR (150 MHz, CDCl3) δ 171.3, 166.9, 152.9, 150.1, 136.9, 134.9, 134.0, 131.5, 129.2×2,
129.2×2, 128.6×2, 128.6×2, 128.5×2, 127.5, 127.3, 127.0×2, 126.7, 120.3, 114.0, 113.5, 65.7, 57.2,
56.6, 55.9, 50.2, 39.0, 37.0.
4.3.42 (R)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 5-dimethoxyphenylsulfonamido)-3-phenyl
propanoate (11b)
1
mp: 143-144 ºC; yield: 61.2 %; []2D0 71.5 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.69 (d, J = 7.2 Hz, 2H, ArH), 7.48-7.51 (m, 1H, ArH), 7.40-7.43 (m, 2H, ArH),
7.15-7.36 (m, 9H, ArH), 7.08-7.09 (m, 2H, ArH), 6.95-6.97 (dd, J = 3.0 Hz, 9.0 Hz, 1H, ArH),
6.80 (d, J = 9.0 Hz, 1H, ArH), 6.37 (d, 1H, J = 8.4 Hz, CONH), 5.53 (d, J = 7.2 Hz, 1H, CONH),
4.44 (m, 1H, 4-H), 4.25-4.29 (dd, J = 14.4, 7.2 Hz, 1H, 3a-H), 4.06-4.09 (dd, J = 11.4, 4.2 Hz, 1H,
2-H), 4.03-4.05 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.72 (s, 3H, -OCH3), 3.70 (s, 3H, -OCH3),
3.06-3.09 (dd, J = 10.8, 6.6 Hz, 1H, 1a-H), 3.03-3.06 (dd, J = 10.8, 6.6 Hz, 1H, 1b-H), 2.84-2.88
(dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.68-2.72 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.43 (S)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 5-dimethoxyphenylsulfonamido)-3-phenyl

propanoate (11c)
1
mp: 150-153 ºC; yield: 64.5 %; []2D0 35.1 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.72 (d, J = 7.2 Hz, 2H, ArH), 7.47-7.49 (m, 1H, ArH), 7.40-7.42 (m, 2H, ArH),
7.14-7.34 (m, 9H, ArH), 7.07-7.08 (m, 2H, ArH), 7.00-7.02 (dd, J = 3.6 Hz, 9.0 Hz, 1H, ArH),
6.81 (d, J = 9.0 Hz, 1H, ArH), 6.49 (d, 1H, J = 8.4 Hz, CONH), 5.49 (d, J = 6.6 Hz, 1H, CONH),
4.50 (m, 1H, 4-H), 4.25-4.28 (dd, J = 11.4, 3.0 Hz, 1H, 3a-H), 4.18-4.21 (dd, J = 13.8, 6.6 Hz, 1H,
2-H), 3.89-3.91 (dd, J = 11.4, 3.6 Hz, 1H, 3b-H), 3.74 (s, 3H, -OCH3), 3.68 (s, 3H, -OCH3),
3.06-3.08 (m, 2H, 1-H), 2.89-2.92 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.76-2.79 (dd, J = 13.8, 7.8 Hz,
1H, 5b-H).
4.3.44 (S)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 5-dimethoxyphenylsulfonamido)-3-phenyl
propanoate (11d)
1
mp: 144-145 ºC; yield: 67.1 %; []2D0 -71.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.69 (d, J = 7.2 Hz, 2H, ArH), 7.48-7.51 (m, 1H, ArH), 7.40-7.43 (m, 2H, ArH),
7.15-7.36 (m, 9H, ArH), 7.08-7.09 (m, 2H, ArH), 6.95-6.97 (dd, J = 3.0 Hz, 9.0 Hz, 1H, ArH),
6.80 (d, J = 9.0 Hz, 1H, ArH), 6.37 (d, 1H, J = 8.4 Hz, CONH), 5.53 (d, J = 7.2 Hz, 1H, CONH),
4.44 (m, 1H, 4-H), 4.25-4.29 (dd, J = 14.4, 7.2 Hz, 1H, 3a-H), 4.06-4.09 (dd, J = 11.4, 4.2 Hz, 1H,
2-H), 4.03-4.05 (dd, J = 11.4, 4.2 Hz, 1H, 3b-H), 3.72 (s, 3H, -OCH3), 3.70 (s, 3H, -OCH3),
3.06-3.09 (dd, J = 10.8, 6.6 Hz, 1H, 1a-H), 3.03-3.06 (dd, J = 10.8, 6.6 Hz, 1H, 1b-H), 2.84-2.88
(dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.68-2.72 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.45 (R)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 4-dimethoxyphenylsulfonamido)-3-phenyl
propanoate (12a)
mp: 153-154 ºC; yield: 69.1 %; [] 2D0 -28.3 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C33H34N2O7SNa, Calcd. 625.1984 [M+Na]+, found: 625.1984; H NMR (600 MHz, CDCl3): 
7.69-7.73 (m, 3H, ArH), 7.40-7.49 (m, 3H, ArH), 7.07-7.29 (m, 10H, ArH), 6.35-6.54 (m, 2H,
ArH), 6.43 (d, 1H, J = 7.8 Hz, CONH), 5.35 (d, J = 6.0 Hz, 1H, CONH), 4.49 (m, 1H, 4-H),
4.29-4.31 (dd, J = 10.8, 2.4 Hz, 1H, 3a-H), 4.09-4.12 (dd, J = 13.2, 6.6 Hz, 1H, 2-H), 3.85-3.88
(dd, J = 11.4, 3.0 Hz, 1H, 3b-H), 3.80 (s, 3H, -OCH3), 3.67 (s, 3H, -OCH3), 3.05 (m, 2H, 1-H),
2.88-2.91 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.76-2.79 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H); 13C NMR
(150 MHz, CDCl3) δ 171.2, 167.0, 165.0, 157.7, 137.2, 135.1, 134.2, 131.6, 131.4, 129.2×2,
129.1×2, 128.7×2, 128.6×2, 128.4×2, 127.4, 127.1×2, 126.7, 118.6, 104.0, 99.3, 65.4, 57.5, 56.0,

55.6, 50.0, 38.9, 37.0.
4.3.46 (R)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 4-dimethoxyphenylsulfonamido)-3-phenyl
propanoate (12b)
1
mp: 148-149ºC; yield: 60.8 %; []2D0 57.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.62-7.65 (m, 3H, ArH), 7.34-7.44 (m, 3H, ArH), 7.02-7.22 (m, 10H, ArH), 6.28-6.29
(m, 2H, ArH), 6.33 (d, 1H, J = 7.8 Hz, CONH), 5.34 (d, J = 7.2 Hz, 1H, CONH), 4.38 (m, 1H,
4-H), 4.12-4.15 (dd, J = 13.8, 7.2 Hz, 1H, 3a-H), 3.94-3.97 (dd, J = 11.4, 4.2 Hz, 1H, 2-H),
3.88-3.90 (dd, J = 11.4, 3.0 Hz, 1H, 3b-H), 3.71 (s, 3H, -OCH3), 3.64 (s, 3H, -OCH3), 2.97 (d, J =
6.6 Hz, 2H, 1-H), 2.71-2.75 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.57-2.61 (dd, J = 13.8, 7.8 Hz, 1H,
5b-H).
4.3.47 (S)-(R)-2-Benzamido-3-phenylpropyl 2-(2, 4-dimethoxyphenylsulfonamido)-3-phenyl
propanoate (12c)
1
mp: 150-152 ºC; yield: 59.8 %; []2D0 27.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.69-7.73 (m, 3H, ArH), 7.40-7.49 (m, 3H, ArH), 7.07-7.29 (m, 10H, ArH), 6.35-6.54
(m, 2H, ArH), 6.43 (d, 1H, J = 7.8 Hz, CONH), 5.35 (d, J = 6.0 Hz, 1H, CONH), 4.49 (m, 1H,
4-H), 4.29-4.31 (dd, J = 10.8, 2.4 Hz, 1H, 3a-H), 4.09-4.12 (dd, J = 13.2, 6.6 Hz, 1H, 2-H),
3.85-3.88 (dd, J = 11.4, 3.0 Hz, 1H, 3b-H), 3.80 (s, 3H, -OCH3), 3.67 (s, 3H, -OCH3), 3.05 (m, 2H,
1-H), 2.88-2.91 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.76-2.79 (dd, J = 13.8, 7.8 Hz, 1H, 5b-H).
4.3.48 (S)-(S)-2-Benzamido-3-phenylpropyl 2-(2, 4-dimethoxyphenylsulfonamido)-3-phenyl
propanoate (12d)
1
mp: 146-147 ºC; yield: 63.4 %; []2D0 -56.3 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.62-7.65 (m, 3H, ArH), 7.34-7.44 (m, 3H, ArH), 7.02-7.22 (m, 10H, ArH), 6.28-6.29
(m, 2H, ArH), 6.33 (d, 1H, J = 7.8 Hz, CONH), 5.34 (d, J = 7.2 Hz, 1H, CONH), 4.38 (m, 1H,
4-H), 4.12-4.15 (dd, J = 13.8, 7.2 Hz, 1H, 3a-H), 3.94-3.97 (dd, J = 11.4, 4.2 Hz, 1H, 2-H),
3.88-3.90 (dd, J = 11.4, 3.0 Hz, 1H, 3b-H), 3.71 (s, 3H, -OCH3), 3.64 (s, 3H, -OCH3), 2.97 (d, J =
6.6 Hz, 2H, 1-H), 2.71-2.75 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.57-2.61 (dd, J = 13.8, 7.8 Hz, 1H,
5b-H).
4.3.49 (R)-(S)-2-Benzamido-3-phenylpropyl
2-(2-nitro-4-(trifuoromethyl)phenylsulfonamido)-3-phenyl propanoate (13a)
mp: 141-142 ºC; yield: 54.3 %; [] 2D0 -25.3 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:

1
C32H28F3N3O7SNa, Calcd. 678.1498 [M+Na]+, found: 678.1498; H NMR (600 MHz, CDCl3): 
7.93 (s, 1H, ArH), 7.93 (d, J = 7.8 Hz, 1H, ArH), 7.79 (d, J = 7.8 Hz, 1H, ArH), 7.70 (d, J = 7.2
Hz, 2H, ArH), 7.47-7.50 (m, 1H, ArH), 7.39-7.41 (m, 2H, ArH), 7.21-7.33 (m, 5H, ArH),
7.03-7.06 (m, 5H, ArH), 6.37 (d, 1H, J = 7.8 Hz, CONH), 6.03 (d, J = 4.2 Hz, 1H, CONH), 4.64
(m, 1H, 4-H), 4.40-4.43 (dd, J = 13.2, 7.8 Hz, 1H, 3a-H), 4.26-4.29 (dd, J = 10.8, 2.4 Hz, 1H,
2-H), 4.14-4.17 (dd, J = 10.8, 4.2 Hz, 1H, 3b-H), 3.19-3.22 (dd, J = 13.8, 4.8 Hz, 1H, 1a-H),
2.94-2.99 (m, 2H, 1b-H, 5a-H), 2.87-2.91 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H); 13C NMR (150 MHz,
CDCl3) δ 170.4, 167.1, 147.1, 137.4, 136.6, 134.9, 133.8, 131.7, 130.8, 129.7, 129.7, 129.1×2,
129.0×2, 128.7×2, 128.6×4, 127.4, 126.9×2, 122.8, 122.6, 121.1, 66.3, 58.4, 49.7, 38.3, 37.2.
4.3.50 (R)-(R)-2-Benzamido-3-phenylpropyl
2-(2-nitro-4-(trifuoromethyl)phenylsulfonamido)-3-phenyl propanoate (13b)
1
mp: 136-138 ºC; yield: 50.3 %; []2D0 49.4 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.97 (s, 1H, ArH), 7.91 (d, J = 7.8 Hz, 1H, ArH), 7.78 (d, J = 8.4 Hz, 1H, ArH), 7.71 (d,
J = 8.4 Hz, 2H, ArH), 7.48-7.51 (m, 1H, ArH), 7.41-7.43 (m, 2H, ArH), 7.21-7.32 (m, 5H, ArH),
7.02-7.06 (m, 5H, ArH), 6.39 (d, 1H, J = 8.4 Hz, CONH), 6.02 (d, J = 9.0 Hz, 1H, CONH), 4.62
(m, 1H, 4-H), 4.49-4.53 (dd, J = 13.8, 9.0 Hz, 1H, 3a-H), 4.26-4.28 (dd, J = 10.8, 3.6 Hz, 1H,
2-H), 4.14-4.17 (dd, J = 10.8, 4.8 Hz, 1H, 3b-H), 3.20-3.23 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H),
2.87-2.99 (m, 3H, 1b-H, 5-H).
4.3.51 (S)-(R)-2-Benzamido-3-phenylpropyl
2-(2-nitro-4-(trifuoromethyl)phenylsulfonamido)-3-phenyl propanoate (13c)
mp: 143-144 ºC; yield: 56.8 %; []2D0 25.1 (c 0.4 CHCl3/MeOH=1:1，v/v); 1H NMR (600 MHz,
CDCl3):  7.93 (s, 1H, ArH), 7.93 (d, J = 7.8 Hz, 1H, ArH), 7.79 (d, J = 7.8 Hz, 1H, ArH), 7.70 (d,
J = 7.2 Hz, 2H, ArH), 7.47-7.50 (m, 1H, ArH), 7.39-7.41 (m, 2H, ArH), 7.21-7.33 (m, 5H, ArH),
7.03-7.06 (m, 5H, ArH), 6.37 (d, 1H, J = 7.8 Hz, CONH), 6.03 (d, J = 4.2 Hz, 1H, CONH), 4.64
(m, 1H, 4-H), 4.40-4.43 (dd, J = 13.2, 7.8 Hz, 1H, 3a-H), 4.26-4.29 (dd, J = 10.8, 2.4 Hz, 1H,
2-H), 4.14-4.17 (dd, J = 10.8, 4.2 Hz, 1H, 3b-H), 3.19-3.22 (dd, J = 13.8, 4.8 Hz, 1H, 1a-H),
2.94-2.99 (m, 2H, 1b-H, 5a-H), 2.87-2.91 (dd, J = 13.8, 7.2 Hz, 1H, 1b-H).
4.3.52 (S)-(S)-2-Benzamido-3-phenylpropyl
2-(2-nitro-4-(trifuoromethyl)phenylsulfonamido)-3-phenyl propanoate (13d)
1
mp: 136-137 ºC; yield: 51.8 %; []2D0 -52.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,

CDCl3):  7.97 (s, 1H, ArH), 7.91 (d, J = 7.8 Hz, 1H, ArH), 7.78 (d, J = 8.4 Hz, 1H, ArH), 7.71 (d,
J = 8.4 Hz, 2H, ArH), 7.48-7.51 (m, 1H, ArH), 7.41-7.43 (m, 2H, ArH), 7.21-7.32 (m, 5H, ArH),
7.02-7.06 (m, 5H, ArH), 6.39 (d, 1H, J = 8.4 Hz, CONH), 6.02 (d, J = 9.0 Hz, 1H, CONH), 4.62
(m, 1H, 4-H), 4.49-4.53 (dd, J = 13.8, 9.0 Hz, 1H, 3a-H), 4.26-4.28 (dd, J = 10.8, 3.6 Hz, 1H,
2-H), 4.14-4.17 (dd, J = 10.8, 4.8 Hz, 1H, 3b-H), 3.20-3.23 (dd, J = 13.8, 5.4 Hz, 1H, 1a-H),
2.87-2.99 (m, 3H, 1b-H, 5-H).
4.3.53 (R)-(S)-2-Benzamido-3-phenylpropyl
2-(4-nitro-3-(trifuoromethyl)phenylsulfonamido)-3-phenyl propanoate (14a)
mp: 160-162 ºC; yield: 54.7 %; [] 2D0 -27.4 (c 0.4 CHCl3/MeOH=1:1 ， v/v); HR-MS:
1
C32H28F3N3O7SNa, Calcd. 678.1498 [M+Na]+, found: 678.1499; H NMR (600 MHz, CDCl3): 
7.67-7.75 (m, 3H, ArH), 7.41-7.51 (m, 4H, ArH), 7.07-7.33 (m, 11H, ArH), 6.47 (d, 1H, J = 7.2
Hz, CONH), 4.98 (d, J = 6.6 Hz, 1H, CONH), 4.57 (m, 1H, 4-H), 4.19-4.22 (dd, J = 11.4, 6.0 Hz,
1H, 3a-H), 4.14-4.17 (dd, J = 10.8, 4.2 Hz, 1H, 3b-H), 4.09-4.11 (dd, J = 11.4, 3.0 Hz, 1H, 2-H),
3.07 (d, J = 6.0 Hz, 2H, 1-H), 2.92-2.96 (dd, J = 13.8, 6.6 Hz, 1H, 5a-H), 2.81-2.85 (dd, J = 13.8,
7.8 Hz, 1H, 5b-H); 13C NMR (150 MHz, CDCl3) δ 170.7, 167.45, 149.62, 144.3, 136.3, 135.1,
133.8, 131.8, 131.4, 129.1×2, 129.0×2, 128.8×2, 128.7×2, 128.6×2, 127.4, 127.1, 126.9×2, 126.5,
126.5, 125.5, 124.2, 66.8, 57.9, 49.7, 38.4, 37.2.
4.3.54 (R)-(R)-2-Benzamido-3-phenylpropyl
2-(4-nitro-3-(trifuoromethyl)phenylsulfonamido)-3-phenyl propanoate (14b)
1
mp: 158-160 ºC; yield: 56.6 %; []2D0 55.2 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.74-7.75 (m, 3H, ArH), 7.41-7.51 (m, 4H, ArH), 7.14-7.31 (m, 11H, ArH), 6.46 (d, 1H,
J = 7.8 Hz, CONH), 4.98 (d, J = 6.6 Hz, 1H, CONH), 4.57 (m, 2H, 4-H, 3a-H), 4.31 (m, 1H,
3b-H), 4.09-4.11 (dd, J = 11.4, 3.0 Hz, 1H, 2-H), 3.07 (d, J = 6.6 Hz, 2H, 1-H), 2.93-2.96 (dd, J =
13.8, 6.0 Hz, 1H, 5a-H), 2.77-2.81 (dd, J = 13.8, 6.4 Hz, 1H, 5b-H).
4.3.55 (S)-(R)-2-Benzamido-3-phenylpropyl
2-(4-nitro-3-(trifuoromethyl)phenylsulfonamido)-3-phenyl propanoate (14c)
1
mp: 163-167 ºC; yield: 50.0 %; []2D0 27.8 (c 0.4 CHCl3/MeOH=1:1，v/v); H NMR (600 MHz,
CDCl3):  7.67-7.75 (m, 3H, ArH), 7.41-7.51 (m, 4H, ArH), 7.07-7.33 (m, 11H, ArH), 6.47 (d, 1H,
J = 7.2 Hz, CONH), 4.98 (d, J = 6.6 Hz, 1H, CONH), 4.57 (m, 1H, 4-H), 4.19-4.22 (dd, J = 11.4,
6.0 Hz, 1H, 3a-H), 4.14-4.17 (dd, J = 10.8, 4.2 Hz, 1H, 3b-H), 4.09-4.11 (dd, J = 11.4, 3.0 Hz, 1H,