Synthesis and anti-HBV activity of novel 3′-N-phenylsulfonyl docetaxel analogs

Article abstract of DOI:10.3390/molecules180910189

Nine new 3′-N-phenylsulfonyl docetaxel analogs were synthesized in good yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg secretion than the positive control lamivudine. Further extensive SAR and mechanistic studies will be reported in due course.

Full text of DOI:10.3390/molecules180910189

Molecules 2013, 18, 10189-10212; doi:10.3390/molecules180910189
OPEN ACCESS
molecules
ISSN 1420-3049
www.mdpi.com/journal/molecules
Article
Synthesis and Anti-HBV Activity of Novel 3′-N-phenylsulfonyl
Docetaxel Analogs
Jun Chang, Yun-Peng Hao, Xiao-Dong Hao, Hong-Fu Lu, Jian-Ming Yu and Xun Sun *
Department of Natural Products Chemistry, School of Pharmacy, Fudan University,
Shanghai 201203, China
* Author to whom correspondence should be addressed; E-Mail: sunxunf@shmu.edu.cn.
Tel./Fax: +86-21-5198-0003.
Received: 13 June 2013; in revised form: 15 August 2013 / Accepted: 17 August 2013 /
Published: 22 August 2013
Abstract: Nine new 3′-N-phenylsulfonyl docetaxel analogs were synthesized in good
yields from the key intermediate N-phenylsulfonyl oxazolidine via a six-step route. These
analogs were tested for anti-hepatitis B virus (HBV) activity in vitro. Compounds 3e, 3g
and 3j showed more potent inhibitory activity against HBeAg secretion than the
positive control lamivudine. Further extensive SAR and mechanistic studies will be reported
in due course.
Keywords: 3′-N-phenylsulfonyl; docetaxel analogs; synthesis; anti-HBV
1. Introduction
Hepatitis B virus (HBV) is a major cause of acute and chronic hepatitis which can lead to liver
cirrhosis, liver failure and hepatocellular carcinoma [1]. It was estimated there are 350 million chronic
carriers and that about 2 billion people have been infected, and an estimated 600,000 to 1.2 million
people die each year from HBV-associated illnesses [2,3]. Currently, therapies for HBV infection on
market include immuno-modulators, interferons (interferon-alpha and pegylated interferon) and nucleoside
analogues. However, these drugs still have their drawbacks. For example, immune-modulators (IFN-a
and pegIFN-a) and polymerase inhibitors (lamivudine, entecavir, telbivudine and adefovir) are
associated with a low cure rate, viral resistance, poor tolerability, and inefficiency in eradicating
HBV [4–7]. Therefore, there is a need to search for new anti-HBV agents with novel antiviral targets
and mechanisms of action.

Molecules 2013, 18
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Natural products and their derivatives have always played a pivotal role as leads in drug discovery.
Paclitaxel (1, Figure 1) and its semi-synthetic derivative docetaxel (Taxotere, 2), are currently
considered to be the most important and promising anticancer agents in the treatment of refractory
breast and ovarian cancers due to their unique mechanism of action by binding tubulin and stabilizing
microtubule formation, which ultimately disrupts mitosis and causes cell death [8]. In our studies of
docetaxel derivatives as anticancer agents [9,10], many analogs were synthesized, including one
3′-N-phenylsulfonyl docetaxel analog. It was found that this 3′-N-phenylsulfonyl docetaxel analog
didn’t show any potent antitumor activity [11,12]. However, it has been reported that a large number of
structurally novel sulfonamide derivatives have shown substantial antiviral activity both in vitro and
in vivo [13,14]. Accordingly, a series of novel 3′-N-phenylsulfonyl docetaxel analogs were designed,
synthesized and investigated for their HBV inhibitory activity. It was hoped that a promising lead
could be emerged from this type of structure.
Figure 1. Structure of paclitaxel, docetaxel and 3′-N-phenylsulfonyl docetaxel analogs.
2
R O
O
HO
O
OH
OH
O
R S
O
O
1
R
NH
3'
NH
O
O
O
O
H
O
H
O
OAc
OAc
HO
HO
OH
OBz
OBz
OH
1
2
1 paclitaxel R = Ph, R = Ac
3
1
2
2 docetaxel R = t-BuO, R = H
2. Results and Discussion
2.1. Chemistry
In order to synthesize these 3′-N-phenylsulfonyl docetaxel analogues, several synthetic routes were
approached. The first attempt was to couple the intermediate N-de-tert-butoxy-carbonyl-7,10-ditroc-
docetaxel (4) with phenylsulfonyl chloride directly (Scheme 1).
Scheme 1. Attempted synthesis of compound 5.
TrocO
O
OTroc
O
S
Ph
NH
O
O
O
H
TrocO
O
O
OTroc
OAc
HO
OBz
OH
2
NH2
O
5
O
H
O
TrocO
O
OTroc
OAc
O
S
HO
OBz
OH
Ph
NH
O
5'
O
2
4
O
H
O
OAc
HO
OBz

Molecules 2013, 18
10191
However, ESIMS of the product showed a quasimolecular ion peak at m/z 852 [M+Na]+, indicating
a molecular weight of 829, or 18 Da lower than that of 5. Since the H-3′ peak had disappeared in
1H-NMR spectrum, it was suggested that the dehydrated product 5′ was obtained rather than 5. Obviously
the elimation occurred quickly since the benzenesulfonate is a very good leaving group formed by
phenylsulfonyl and hydroxyl groups.
The second attempt was to synthesize the side chain from (2R,3S)-3-amino-2-hydroxy-3-phenyl-
propionic acid methyl ester (6), as illustrated in Scheme 2. Compound 6 was transformed into
phenylsulfonamide 7 with phenylsulfonyl chloride, followed by saponification to afford acid 8.
However, the coupling reaction between 8 and the intermediate 7,10-ditroc-10-deacetylbaccatin failed
to yield 5, partially because 8 was more prone to undergo self-condensation due to the steric hindrance
of the hydroxyl group in 10-DAB. Since the free hydroxyl group in 7 interfered with the reaction, we
decided to protect it first. Thus, after protecting the hydroxyl group of 7 with 2,2,2-trichloroethyl
chloroformate (TrocCl) followed by saponification, the carboxylic acid 10 was obtained as expected.
However, the desired product 5′′ was still not formed when 10 reacted with 7,10-ditroc-10-DAB.
Scheme 2. Another attempted synthesis of compound 5.
O
S
O
S
O
S
Ph
Cl
Ph
Ph
NH2
7,10-ditroc-10-DAB
O
NH
NH
LiOH
O
O
O
O
O
5
O
OH
O
OH
OH
OH
8
6
7
TrocCl
LiOH
TrocO
HO
O
OTroc
O
O
O
S
Ph
S
7,10-ditroc-10-DAB
Ph
S
NH
O
Ph
NH
O
NH
O
O
O
O
O
H
O
OAc
OH
OTroc
O
OBz
OTroc
OTroc
10
5''
9
Ke et al. reported the synthesis of novel 3′-N-tert-butylsulfonyl analogs of docetaxel by asymmetric
synthesis of the side chain oxazolidine and condensing this oxazolidine with 7,10-ditroc-10-DAB [12].
Unfortunately, the oxazolidine is only obtained as diastereomeric mixtures via five steps from
(R)-tert-butylsulfinylimine. We previously reported the synthesis of fluorinated docetaxel derivatives
from the enantiopure N-Boc oxazolidine side chain [9,10]. Therefore, N-phenylsulfonyl oxazolidine could
be used as an important intermediate for this condensation reaction. Finally, compounds 3a–j were
synthesized via a new six-step route in good yields from (2R,3S)-3-amino-2-hydroxy-3-phenyl-propionic
acid methyl ester (6), a commercially available starting material, as illustrated in Scheme 3. Compound 6
was first transformed into phenylsulfonamides 7a–j with phenylsulfonyl chloride. Cyclic protection
using methoxypropene in the presence of a catalytic amount of pyridinium para-toluenesulfonate
(PPTS) followed by saponification of the formed intermediates 11a–j afforded acids 12a–j in
80%–95% yields. Then, key intermediates 12a–j were coupled with 7,10-ditroc-10-DAB in the presence
of dicyclohexylcarbodiimide (DCC) and 4-dimethylaminopyridine (DMAP) to provide the corresponding
intermediates 13a–j in 85%–95% yields. After removing the acetonide protecting group of 13a–j with
98% formic acid at room temperature, intermediates 5a–j were obtained in 57%–85% yields. After further

Molecules 2013, 18
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deprotection of the 7,10-ditroc protecting groups on 5a–j with zinc in acetic acid, 3′-N-phenylsulfonyl
docetaxel analogs 3a–j were synthesized in 53%–80% yields.
Scheme 3. Synthesis of compounds 3a–j.
O
S
O
S
O
S
R
R
R
NH
N
O
2
NH
O
N
O
O
O
O
O
c
OH
b
a
O
O
O
OH
O
OH
O
12a-j
11a-j
7a-j
6
TrocO
O
TrocO
O
OTroc
OTroc
O
O
O
R
S
NH
R
S
O
O
N
O
e
O
O
d
H
O
H
O
OAc
OAc
HO
HO
OBz
OH
OBz
O
5a-j
13a-j
3a R = phenyl
3b R = benzyl
3c R = 4-methylphenyl
HO
O
OH
O
R
S
3d R = 4-methoxylphenyl
3e R = 4-isopropylphenyl
3f R = 4-fluorophenyl
3g R = 4-trifluoromethylphenyl
3h R = 4-chlorophenyl
3i R = 4-bromophenyl
3j R = 2,4,6-trimethylphenyl
NH
O
O
f
O
H
O
OAc
HO
3a-j
OBz
OH
Reagents and conditions: (a) RSO2Cl/Et3N, CH2Cl2, 0 °C-r.t., 1 h; (b) CH2 = C(OCH3)CH3, PPTs, toluene,
85 °C, 2 h; (c) LiOH, THF/H2O, r.t., 1 h; (d) 7,10-ditroc-10-DAB, DCC, DMAP, toluene; 85 °C, 3 h;
(e) HCOOH, r.t., 1.5 h; (f) Zn/HOAc, MeOH, 50 °C, 1 h.
2.2. Anti-HBV Activity
With compounds 3a–j in hand, they were tested for their antiviral activity against hepatitis B virus
(HBV) in vitro [15], and the results are summarized in Table 1.
Table 1. Anti-HBsAg and anti-HBeAg effects of compounds 3a–j in HepG2 2.2.15 cell line.
MNTC b (in μM or µg/mL) HBsAg inhibition (%)
HBeAg inhibition (%)
3a
3b
3c
3d
3e
3f
7.4 (6.25)
14.5 (12.5)
14.5 (12.5)
28.5 (25)
14.1 (12.5)
28.9 (25)
10.7
10.0
0
11.8
0
19.2
34.1
11.4
14.8
44.4
3.0
0
3g
3h
3i
3j
13.7 (12.5)
14.2 (12.5)
13.5 (12.5)
14.1 (12.5)
7.7 (6.25)
7.3 (6.25)
873.4 (200)
0
5.0
0
0
0
47.0
25.8
26.0
40.2
8.2
Docetaxel
Paclitaxel
0
10.9
5.3
12.5
3TC a
a
b
Positive control (3TC = Lamivudine); Maximum non-toxic concentration. Cell damage was assessed by
means of the MTT assay; cell growth inhibition ≥25% was considered as cytotoxic.

Molecules 2013, 18
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Overall, the compounds showed only weak or no inhibitory activity on HBsAg secretion, except for
compounds 3c and 3f, 3a–b, 3d–e and 3g–j that exhibited more potency against HBeAg secretion than
the positive control lamivudine (12.5% at 873.4 μM). Especially, 3e, 3g and 3j showed inhibitory
activity on HBeAg secretion by 44.4%, 47.0% and 40.2% at the maximum non-toxic concentration
(12.5 μg/mL), respectively.
Preliminary structure-activity relationships (SAR) did not show a clear trend in terms of
electron-withdrawing or electron-donating substituents on the phenyl ring. Only phenyl (3a),
4-methoxyl (3d), 4-chloro (3h) and benzyl (3b) analogs exihibited weaker inhibitory activity against
both HBsAg secretion and HBeAg secretion. However, 4-isopropyl (3e), 4-trifluoromethyl (3g) and
2,4,6-trimethyl (3j) analogs demonstrated the most potent inhibitory activity against HBeAg secretion.
Meanwhile, they were all inactive against HBsAg secretion. Accordingly, further extensive SAR study
on the substituent pattern on phenyl ring and modification of the linker (based on the result of 3b) will
be continued in the near future.
3. Experimental
3.1. General
Reagents were purchased from the Aldrich (Shanghai, China) and TCI Chemical (Shanghai, China)
companies. All solvents are purified and dried in accordance with standard procedures, unless
otherwise indicated. Reactions were monitored by TLC using Yantai (Yantai, China) GF254 silica gel
plates (5 × 10 cm). Silica gel column chromatography was performed on silica gel (300–400 mesh)
from Yantai. Melting points (mp) were determined using an X-4 microscope melting point apparatus
and were uncorrected. All NMR spectra were recorded on a Bruker DRX-400 (400/100 MHz)
spectrometer. Low-resolution mass spectra (ESI) were performed on a Shimadzu LCMS-2010EV and
high-resolution mass spectra on a Bruker Daltonics, Inc. APEXIII7.0 TESLA FMS (ESI). Elemental
analysis was carried out on an Elementar Vario EL instrument.
3.2. Synthesis
3.2.1. General Procedure for the Synthesis of 7a–j
To a round-bottomed flask (2R,3S)-3-amino-2-hydroxy-3-phenyl-propionic acid methyl ester
o
(6, 0.39 g, 2 mmol) was added into THF (15 mL), which was cooled to 0 C. To this suspension was
added Et3N (1.11 mL, 8 mmol), followed by the dropwise addition of phenylsulfonyl chloride
(2.2 mmol). After further stirred at this temperature for 1 h, it was diluted with DCM (30 mL). The
organic layer was washed with brine, dried over anhydrous Na2SO4 and filtered. Then the filtrate was
evaporated and the residue was purified by column chromatography using petroleum ether/EtOAc
(2/1) to afford the products 7a–j as white solids.
2-Hydroxy-3-benzenesulfonylamino-3-phenyl-propionic acid methyl ester (7a). Yield 59% (395 mg);
1H-NMR (CD3COCD3): δ 3.60 (s, 3H, OCH3), 4.35 (d, 1H, J = 3.2 Hz, 2-CH), 4.88 (d, 1H, J = 3.2 Hz,
3-CH), 7.14 (m, 3H, 3-Ph), 7.27 (m, 2H, 3-Ph), 7.35 (t, 2H, J = 7.6 Hz, m-PhSO2), 7.46 (t, 1H, J = 7.6 Hz,
p-PhSO2), 7.66 (t, 2H, J = 7.6 Hz, PhSO2); 13C-NMR (CD3COCD3): δ 172.72, 142.67, 139.31, 132.76,

Molecules 2013, 18
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129.44, 128.72, 128.26, 128.07, 127.63, 75.45, 60.92, 52.52; ESI-MS (m/z): 336 [M + H]+. HRMS
(ESI) m/z calcd. for C16H17NO5SNa [M + Na]+: 358.0725, found 358.0704.
2-Hydroxy-3-phenylmethane sulfonylamino-3-phenyl-propionic acid methyl ester (7b). Yield 59%
1
(412 mg); H-NMR (CD3COCD3): δ 3.69 (s, 3H, OCH3), 4.01 (d, 1H, J = 13.2 Hz, CH2 in Bn),
4.13 (d, 1H, J = 14.0 Hz, CH2 in Bn), 4.44 (d, 1H, J = 4.0 Hz, 2-CH), 4.93 (d, 1H, J = 3.6 Hz, 3-CH),
13
7.19 (m, 2H, 3-Ph), 7.27 (m, 3H, 3-Ph), 7.39 (m, 3H, Ph in Bn), 7.52 (m, 2H, Ph in Bn); C-NMR
(CD3COCD3): 172.92, 140.33, 131.73, 130.88, 129.21, 129.03, 128.85, 128.66, 128.61, 75.63, 61.10,
60.41, 52.56; ESI-MS (m/z): 350 [M + H]+. HRMS (ESI) m/z calcd. for C17H19NO5SNa [M + Na]+:
372.0882, found 372.0859.
2-Hydroxy-3-(4-methyl benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7c). Yield 64%
1
(448 mg); H-NMR (CD3COCD3): δ 2.31 (s, 3H, CH3 in Tosyl), 3.60 (s, 3H, OCH3), 4.34 (d, 1H,
J = 2.8 Hz, 2-CH), 4.84 (d, 1H, J = 3.6 Hz, 3-CH), 7.27 (m, 5H, 3′-Ph), 7.26 (m, 2H, Ph in Tosyl),
7.53 (d, 2H, J = 8.0 Hz, Ph in Tosyl); 13C-NMR (CD3COCD3): 172.73, 143.39, 139.45, 129.92,
128.70, 128.29, 127.96, 127.73, 75.45, 60.87, 52.50, 21.29; ESI-MS (m/z): 350 [M + H]+. HRMS
(ESI) m/z calcd. for C17H19NO5SNa [M + Na]+: 372.0882, found 372.0869.
2-Hydroxy-3-(4-methoxy benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7d). Yield 59%
(432 mg); 1H-NMR (CD3COCD3): δ 3.63 (s, 3H, 3′-CH3), 3.81 (s, 3H, OCH3), 4.33 (d, 1H, J = 4.0 Hz,
2-CH), 4.83 (d, 1H, J = 3.2 Hz, 3-CH), 6.85 (m, 2H, PhSO2), 7.15 (m, 3H, 3-Ph), 7.26 (m, 2H, 3-Ph),
7.57 (m, 2H, PhSO2); 13C-NMR (CD3COCD3): 172.74, 163.31, 139.38, 134.30, 129.78, 128.94,
128.70, 128.29, 114.52, 75.50, 60.86, 55.98, 52.53; ESI-MS (m/z): 366 [M + H]+. HRMS (ESI) m/z
calcd. for C17H19NO6SNa [M + Na]+: 388.0831, found 388.0837.
2-Hydroxy-3-(4-isopropyl benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7e). Yield
59% (445 mg); 1H-NMR (CD3COCD3): δ 1.19 (d, 6H, J = 3.2 Hz, 2CH3 in i-PrPh), 2.89 (m, 1H, CH in
i-PrPh), 3.61 (s, 3H, OCH3), 4.34 (d, 1H, J = 3.2 Hz, 2-CH), 4.85 (d, 1H, J = 2.8 Hz, 3-CH), 7.12 (m,
3H, 3-Ph), 7.19 (d, 2H, J = 8.4 Hz, PhSO2), 7.23 (m, 2H, 3-Ph), 7.40 (m, 2H, PhSO2); 13C-NMR
(CD3COCD3): 172.74, 154.05, 139.99, 139.20, 128.66, 128.31, 127.97, 127.87, 127.38, 75.44, 60.91,
52.51, 34.74, 23.93; ESI-MS (m/z): 378 [M + H]+. HRMS (ESI) m/z calcd. for C19H23NO5SNa [M + Na]+:
400.1195, found 400.1180.
2-Hydroxy-3-(4-fluoro benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7f). Yield 49%
(346 mg); 1H-NMR (CD3COCD3): δ 3.66 (s, 3H, OCH3), 4.35 (d, 1H, J = 2.8 Hz, 2-CH), 4.88 (d, 1H,
J = 3.2 Hz, 3-CH), 7.08 (t, 2H, J = 8.8 Hz, PhSO2), 7.15 (m, 3H, 3-Ph), 7.26 (m, 2H, 3-Ph), 7.68 (m,
2H, PhSO2); 13C-NMR (CD3COCD3): 172.68, 166.54, 164.06, 138.94, 130.66, 130.57, 128.73, 128.37,
128.10, 116.41, 116.18, 75.41, 61.01, 52.53; ESI-MS (m/z): 354 [M + H]+. HRMS (ESI) m/z calcd. for
C16H16FNO5SNa [M + Na]+: 376.0631, found 376.0618.
2-Hydroxy-3-(4-trifluoromethyl benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7g).
1
Yield 19% (153 mg); H-NMR (CD3COCD3): δ 3.65 (s, 3H, OCH3), 4.37 (d, 1H, J = 3.2 Hz, 2-CH),
4.91 (d, 1H, J = 3.2 Hz, 3-CH), 7.11 (m, 3H, 3-Ph), 7.23 (m, 2H, 3-Ph), 7.66 (d, 2H, J = 8.4 Hz,

Molecules 2013, 18
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13
PhSO2), 7.82 (d, 2H, J = 8.0 Hz, PhSO2); C-NMR (CD3COCD3): 172.62, 146.30, 138.65, 133.69,
133.37, 128.73, 128.54, 128.43, 128.16, 126.52, 126.48, 126.44, 125.90, 123.20, 75.33, 61.19, 52.51;
ESI-MS (m/z): 404 [M + H]+. HRMS (ESI) m/z calcd. for C17H16F3NO5SNa [M + Na]+: 426.0599,
found 426.0606.
2-Hydroxy-3-(4-chloro benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7h). Yield 32%
(236 mg); 1H-NMR (CD3COCD3): δ 3.65 (s, 3H, OCH3), 4.36 (d, 1H, J = 3.2 Hz, 2-CH), 4.88 (d, 1H,
J = 3.2 Hz, 3-CH), 7.15 (m, 3H, 3-Ph), 7.26 (m, 2H, 3-Ph), 7.35 (d, 2H, J = 8.8 Hz, PhSO2), 7.62 (d,
2H, J = 8.8 Hz, PhSO2); 13C-NMR (CD3COCD3): 172.65, 141.42, 138.98, 138.36, 129.49, 128.74,
128.39, 128.10, 75.38, 61.05, 52.51; ESI-MS (m/z): 370 [M + H]+. HRMS (ESI) m/z calcd. for
C16H16ClNO5SNa [M + Na]+: 392.0335, found 392.0342.
2-Hydroxy-3-(4-bromo benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7i). Yield 35%
(290 mg); 1H-NMR (CD3COCD3): δ 3.64 (s, 3H, OCH3), 4.36 (d, 1H, J = 3.2 Hz, 2-CH), 4.88 (d, 1H,
J = 3.2 Hz, 3-CH), 7.16 (m, 3H, 3-Ph), 7.26 (m, 2H, 3-Ph), 7.51 (m, 4H, PhSO2); 13C-NMR
(CD3COCD3): 172.65, 141.88, 138.98, 132.51, 129.60, 128.75, 128.40, 128.09, 126.87, 75.37, 61.06,
52.51; ESI-MS (m/z): 413 [M + H]+. HRMS (ESI) m/z calcd. For C16H16BrNO5SNa [M + Na]+:
435.9830, found 435.9807.
2-Hydroxy-3-(2,4,6-trimethyl benzenesulfonylamino)-3-phenyl-propionic acid methyl ester (7j). Yield
1
50% (377 mg); H-NMR (CD3COCD3): δ 2.23 (s, 3H, CH3 in PhSO2), 2.53 (s, 6H, CH3 in PhSO2),
3.45 (s, 3H, OCH3), 4.32 (d, 1H, J = 3.2 Hz, 2-CH), 4.72 (d, 1H, J = 3.2 Hz, 3-CH), 6.90 (s, 2H,
PhSO2), 7.20 (m, 3H, 3-Ph), 7.31 (m, 2H, 3-Ph); 13C-NMR (CD3COCD3): 172.67, 142.56, 139.92,
139.49, 136.23, 132.43, 128.70, 128.11, 128.05, 75.18, 60.45, 52.37, 23.09, 20.74; ESI-MS (m/z): 378
[M + H]+. HRMS (ESI) m/z calcd. for C19H23NO5SNa [M + Na]+: 400.1195, found 400.1180.
3.2.2. General Procedure for the Synthesis of 11a–j
To a stirred solution of 7a–j (0.45 mmol) and PPTs (113 mg, 0.045 mmol) in anhydrous toluene
(8 mL) was added 2-methoxypropene (0.129 mL, 1.35 mmol). The reaction mixture was warmed to
85 °C , and further stirred for 2 h at this temperature. After cooled down to room temperature, the
mixture was diluted with EtOAc (50 mL). The organic layer was washed with brine, dried over
anhydrous Na2SO4 and filtered. The filtrate was evaporated and the residue was purified by silica gel
column chromatography using petroleum ether/EtOAc (2/1) to obtain products 11a–j as colorless liquids.
2,2-Dimethyl-3-benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester (11a). Yield 97%
(164 mg); 1H-NMR (CD3COCD3): δ 1.69 (s, 3H, i-Pr), 1.81 (s, 3H, i-Pr), 3.66 (s, 3H, OCH3), 4.62 (d,
1H, J = 4.8 Hz, 2-CH), 5.27 (d, 1H, J = 4.8 Hz, 3-CH), 7.22 (m, 3H, 3′-Ph), 7.32 (m, 2H, 3′-Ph),
7.42 (t, 2H, J = 7.6 Hz, m-PhSO2), 7.55 (t, 1H, J = 7.6 Hz, p-PhSO2), 7.62 (t, 2H, J = 7.6 Hz,
13
o-PhSO2); C-NMR (CD3COCD3): 171.03, 142.02, 139.51, 133.41, 129.60, 129.14, 128.76, 128.46,
128.32, 100.78, 82.50, 66.19, 52.76, 27.31; ESI-MS (m/z): 376 [M + H]+. HRMS (ESI) m/z calcd. for
C19H21NO5SNa [M + Na]+: 398.1038, found 398.1024.

Molecules 2013, 18
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2,2-Dimethyl-3-phenylmethane sulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester (11b).
1
Yield 92% (161 mg); H-NMR (CD3COCD3): δ 1.60 (s, 3H, i-Pr), 1.73 (s, 3H, i-Pr), 3.79 (s, 3H,
OCH3), 3.79 (d, 1H, J = 14.0 Hz, CH2 in Bn), 4.10 (d, 1H, J = 13.6 Hz, CH2 in Bn), 4.79 (d, 1H,
J = 4.0 Hz, 2-CH), 5.30 (d, 1H, J = 4.4 Hz, 3-CH), 7.25 (m, 2H, 3-Ph), 7.33 (m, 3H, 3-Ph), 7.40 (m,
1H, Ph in Bn), 7.48 (m, 2H, Ph in Bn), 7.58 (m, 2H, Ph in Bn); 13C-NMR (CD3COCD3): 171.57,
140.54, 131.98, 130.12, 129.58, 129.30, 129.14, 128.97, 100.28, 82.18, 65.65, 61.03, 52.88, 28.95,
27.74; ESI-MS (m/z): 390 [M + H]+; Anal. calcd. for C20H23NO5S: C, 61.68; H, 5.95; N, 3.60. Found:
C, 61.73; H, 6.05; N, 3.52.
2,2-Dimethyl-3-(4-methyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester (11c).
Yield 80% (140 mg); 1H-NMR (CD3COCD3): δ 1.68 (s, 3H, i-Pr), 1.79 (s, 3H, i-Pr), 2.36 (s, 3H, CH3
in tosyl), 3.66 (s, 3H, OCH3), 4.60 (d, 1H, J = 4.8 Hz, 2-CH), 5.24 (d, 1H, J = 4.8 Hz, 3-CH), 7.23 (m,
13
5H, 3′-Ph), 7.32 (m, 2H, Ph in tosyl), 7.50 (d, 2H, J = 8.4 Hz, Ph in tosyl); C-NMR (CD3COCD3):
171.04, 144.23, 139.71, 139.12, 130.07, 129.10, 128.62, 128.43, 128.42, 100.68, 82.48, 66.20, 52.75,
27.22, 21.37; ESI-MS (m/z): 390 [M + H]+. HRMS (ESI) m/z calcd. for C20H23NO5SNa [M + Na]+:
412.1195, found 412.1196.
2,2-Dimethyl-3-(4-methoxy)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester (11d).
1
Yield 99% (180 mg); H-NMR (CD3COCD3): δ 1.69 (s, 3H, i-Pr), 1.80 (s, 3H, i-Pr), 3.67 (s, 3H,
3-CH3), 3.85 (s, 3H, OCH3), 4.58 (d, 1H, J = 4.8 Hz, 2-CH), 5.21 (d, 1H, J = 4.8 Hz, 3-CH), 6.89 (m,
13
2H, PhSO2), 7.22 (m, 3H, 3-Ph), 7.29 (m, 2H, 3-Ph), 7.53 (m, 2H, PhSO2); C-NMR (CD3COCD3):
171.06, 163.73, 139.67, 133.52, 130.57, 129.08, 128.63, 128.38, 114.63, 100.65, 82.51, 66.12, 60.57,
56.09, 52.73, 27.15; ESI-MS (m/z): 406 [M + H]+; Anal. calcd. for C20H23NO6S: C, 59.24; H, 5.72; N,
3.45. Found: C, 59.21; H, 5.70; N, 3.49.
2,2-Dimethyl-3-(4-isopropyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester
1
(11e). Yield 97% (182 mg); H-NMR (CD3COCD3): δ 1.22 (d, 6H, J = 7.4 Hz, 2CH3 in i-PrPh), 1.71
(s, 3H, i-Pr), 1.83 (s, 3H, i-Pr), 2.94 (m, 1H, CH in i-PrPh), 3.66 (s, 3H, OCH3), 4.59 (d, 1H, J = 4.8 Hz,
2-CH), 5.21 (d, 1H, J = 5.2 Hz, 3-CH), 7.19 (m, 3H, 3-Ph), 7.24 (d, 2H, J = 8.8 Hz, PhSO2), 7.26 (m,
2H, 3-Ph), 7.49 (d, 2H, J = 8.8 Hz, PhSO2); 13C-NMR (CD3COCD3): 170.14, 153.83, 138.44, 138.35,
128.18, 127.91, 127.68, 127.57, 126.60, 99.98, 81.68, 78.33, 65.24, 51.82, 33.87, 26.42, 23.03, 22.98;
ESI-MS (m/z): 418 [M + H]+. HRMS (ESI) m/z calcd. for C22H27NO5SNa [M + Na]+: 440.1508,
found 440.1501.
2,2-Dimethyl-3-(4-fluoro)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester (11f).
1
Yield 81% (143 mg); H-NMR (CD3COCD3): δ 1.71 (s, 3H, i-Pr), 1.83 (s, 3H, i-Pr), 3.69 (s, 3H,
OCH3), 4.62 (d, 1H, J = 4.8 Hz, 2-CH), 5.23 (d, 1H, J = 4.8 Hz, 3-CH), 7.14 (t, 2H, J = 8.8 Hz,
PhSO2), 7.22 (m, 3H, 3-Ph), 7.29 (m, 2H, 3-Ph), 7.63 (m, 2H, PhSO2); 13C-NMR (CD3COCD3):
171.02, 166.85, 164.35, 139.09, 138.26, 131.43, 131.33, 129.17, 128.82, 128.60, 116.63, 116.40,
100.97, 82.52, 66.07, 52.77, 27.38; ESI-MS (m/z): 394 [M + H]+. HRMS (ESI) m/z calcd. for
C19H20FNO5SNa [M + Na]+: 416.0944, found 416.0936.

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2,2-Dimethyl-3-(4-trifluoromethyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester
(11g). Yield 99% (197 mg); 1H-NMR (CD3COCD3): δ 1.74 (s, 3H, i-Pr), 1.87 (s, 3H, i-Pr), 3.69 (s, 3H,
OCH3), 4.65 (d, 1H, J = 5.2 Hz, 2-CH), 5.26 (d, 1H, J = 4.8 Hz, 3-CH), 7.19 (m, 3H, 3-Ph), 7.26 (m,
2H, 3-Ph), 7.70 (d, 2H, J = 8.4 Hz, PhSO2), 7.76 (d, 2H, J = 8.0 Hz, PhSO2); 13C-NMR (CD3COCD3):
170.90, 145.58, 138.51, 134.14, 129.21, 129.17, 128.95, 128.78, 126.71, 126.68, 126.64, 126.60,
101.24, 82.49, 66.11, 52.79, 27.67; ESI-MS (m/z): 444 [M + H]+; Anal. calcd. for C20H20F3NO5S: C,
54.17; H, 4.55; N, 3.16. Found: C, 54.31; H, 4.51; N, 3.22.
2,2-Dimethyl-3-(4-chloro)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester (11h).
1
Yield 93% (171 mg); H-NMR (CD3COCD3): δ 1.71 (s, 3H, i-Pr), 1.83 (s, 3H, i-Pr), 3.69 (s, 3H,
OCH3), 4.63 (d, 1H, J = 5.2 Hz, 2-CH), 5.24 (d, 1H, J = 5.2 Hz, 3-CH), 7.24 (m, 3H, 3-Ph), 7.29 (m,
2H, 3-Ph), 7.41 (d, 2H, J = 8.8 Hz, PhSO2), 7.56 (d, 2H, J = 8.0 Hz, PhSO2); 13C-NMR (CD3COCD3):
170.99, 140.73, 139.10, 139.02, 130.15, 129.69, 129.21, 128.83, 128.66, 101.01, 82.50, 66.11, 52.79,
27.46; ESI-MS (m/z): 410 [M + H]+. HRMS (ESI) m/z calcd for C19H20ClNO5SNa [M + Na]+:
432.0648, found 432.0653.
2,2-Dimethyl-3-(4-bromo)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester (11i).
1
Yield 99% (202 mg); H-NMR (CD3COCD3): δ 1.71 (s, 3H, i-Pr), 1.83 (s, 3H, i-Pr), 3.69 (s, 3H,
OCH3), 4.63 (d, 1H, J = 5.2 Hz, 2-CH), 5.23 (d, 1H, J = 4.8 Hz, 3-CH), 7.24 (m, 3H, 3-Ph), 7.29 (m,
2H, 3-Ph), 7.49 (d, 2H, J = 8.8 Hz, PhSO2), 7.57 (d, 2H, J = 8.8 Hz, PhSO2); 13C-NMR (CD3COCD3):
170.96, 141.17, 138.99, 132.70, 130.20, 129.21, 128.81, 128.65, 127.67, 101.00, 82.48, 66.10, 52.78,
27.46; ESI-MS (m/z): 455 [M + H]+. HRMS (ESI) m/z calcd. for C19H20BrNO5SNa [M + Na]+:
476.0143, found 476.0156.
2,2-Dimethyl-3-(2,4,6-trimethyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid methyl ester
(11j). Yield 81% (152 mg); 1H-NMR (CD3COCD3): δ 1.82 (s, 3H, i-Pr), 1.92 (s, 3H, i-Pr), 2.10 (s, 3H,
CH3 in PhSO2), 2.51 (s, 6H, CH3 in PhSO2), 3.74 (s, 3H, OCH3), 4.47 (d, 1H, J = 5.6 Hz, 2-CH), 4.99
(d, 1H, J = 6.0 Hz, 3-CH), 6.63 (s, 2H, PhSO2), 7.01 (m, 5H, 3-Ph); 13C-NMR (CD3COCD3): 171.11,
144.03, 140.69, 138.39, 134.00, 132.53, 128.67, 128.25, 127.46, 102.10, 83.12, 66.06, 52.72, 27.12,
23.21, 20.67; ESI-MS (m/z): 418 [M + H]+; Anal. calcd. for C22H27NO5S: C, 63.29; H, 6.52; N, 3.35.
Found: C, 63.42; H, 6.48; N, 3.39.
3.2.3. General Procedure for the Synthesis of 12a–j
To a stirred solution of 11a–j (0.437 mmol) in a mixture of solvent (THF:H2O = 6 mL:2 mL) at 0 °C
was added LiOH•H2O (37 mg, 0.87 mmol). The resulting mixture was warmed to room temperature
and further stirred for 1 h. Then the pH of the mixture was adjusted to 2~3 by adding 1N HCl solution.
After extracted with CH2Cl2 three times, the combined organic phase was dried over anhydrous
Na2SO4 and evaporated to afford the colorless liquid products 12a–j.
2,2-Dimethyl-3-benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12a). Yield 97% (154 mg);
1H-NMR (CD3COCD3): δ 1.71 (s, 3H, i-Pr), 1.83 (s, 3H, i-Pr), 4.56 (d, 1H, J = 4.8 Hz, 2-CH), 5.25 (d,
1H, J = 4.4 Hz, 3-CH), 7.21 (m, 3H, 3′-Ph), 7.31 (m, 2H, 3′-Ph), 7.39 (t, 2H, J = 7.6 Hz, m-PhSO2),

Molecules 2013, 18
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7.53 (t, 1H, J = 7.6 Hz, p-PhSO2), 7.60 (t, 2H, J = 7.6 Hz, o-PhSO2); 13C-NMR (CD3COCD3) δ
171.48, 142.04, 139.68, 133.34, 129.55, 129.12, 128.69, 128.50, 128.305, 100.72, 82.50, 66.24, 27.41;
ESI-MS (m/z): 362 [M + H]+. HRMS (ESI) m/z calcd. for C18H19NO5SNa [M + Na]+: 384.0882,
found 384.0888.
2,2-Dimethyl-3-phenylmethane sulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12b). Yield 97%
(160 mg); 1H-NMR (CD3COCD3): δ 1.61 (s, 3H, i-Pr), 1.76 (s, 3H, i-Pr), 3.79 (d, 1H, J = 14.0 Hz, CH2
in Bn), 4.10 (d, 1H, J = 14.0 Hz, CH2 in Bn), 4.76 (d, 1H, J = 4.0 Hz, 2-CH), 5.30 (d, 1H, J = 4.0 Hz,
3-CH), 7.24 (m, 3H, 3-Ph), 7.33 (m, 2H, 3-Ph), 7.40 (m, 2H, Ph in Bn), 7.59 (m, 3H, Ph in Bn);
13C-NMR (CD3COCD3) δ 172.03, 140.75, 131.99, 131.74, 130.93, 130.15, 129.56, 129.24, 129.15,
129.04, 129.00, 128.83, 128.62, 128.55, 100.23, 82.12, 75.05, 65.72, 27.81; ESI-MS (m/z): 376 [M + H]+.
HRMS (ESI) m/z calcd. for C19H21NO5SNa [M + Na]+: 398.1038, found 398.1031.
2,2-Dimethyl-3-(4-methyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12c). Yield 96%
1
(158 mg); H-NMR (CD3COCD3): δ 1.70 (s, 3H, i-Pr), 1.82 (s, 3H, i-Pr), 2.35 (s, 3H, CH3 in Tosyl),
4.55 (d, 1H, J = 5.2 Hz, 2-CH), 5.22 (d, 1H, J = 5.2 Hz, 3-CH), 7.22 (m, 5H, Ph in Tosyl), 7.30 (m,
2H, Ph in Tosyl), 7.48 (d, 2H, Ph in Tosyl); 13C-NMR (CD3COCD3) δ 171.47, 144.15, 139.91, 139.12,
130.04, 129.09, 128.55, 128.45, 128.44, 100.63, 82.49, 66.23, 27.31, 21.37; ESI-MS (m/z): 376 [M + H]+.
HRMS (ESI) m/z calcd. for C19H21NO5SNa [M + Na]+: 398.1038, found 398.1031.
2,2-Dimethyl-3-(4-methoxy)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12d). Yield 99%
(170 mg); 1H-NMR (CD3COCD3): δ 1.74 (s, 3H, i-Pr), 1.88 (s, 3H, i-Pr), 3.70 (s, 3H, 3-CH3), 4.67 (d,
1H, J = 4.8 Hz, 2-CH), 5.29 (d, 1H, J = 5.2 Hz, 3-CH), 7.21 (m, 3H, 3-Ph), 7.29 (m, 2H, 3-Ph),
13
7.80 (d, 2H, J = 9.2 Hz, PhSO2), 8.19 (d, 2H, J = 8.8 Hz, PhSO2); C-NMR (CD3COCD3) δ 170.87,
150.65, 147.26, 138.47, 129.81, 129.30, 129.06, 128.9, 124.68, 101.32, 82.43, 66.12, 52.85, 27.78;
ESI-MS (m/z): 392 [M + H]+. HRMS (ESI) m/z calcd. for C19H21NO6SNa [M + Na]+: 414.0987,
found 414.0998.
2,2-Dimethyl-3-(4-isopropyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12e). Yield 95%
1
(168 mg); H-NMR (CD3COCD3): δ 1.21 (d, 3H, J = 1.6 Hz, CH3 in i-PrPh), 1.22 (d, 3H, J = 1.2 Hz,
CH3 in i-PrPh), 1.74 (s, 3H, CH3 in i-Pr), 1.85 (s, 3H, CH3 in i-Pr), 2.92 (m, 1H, CH in i-PrPh),
4.53 (d, 1H, J = 5.2 Hz, 2-CH), 5.19 (d, 1H, J = 5.2 Hz, 3-CH), 7.16 (m, 3H, 3-Ph), 7.20 (d, 2H,
J = 8.4 Hz, PhSO2), 7.23 (m, 2H, 3-Ph), 7.46 (m, 2H, PhSO2); 13C-NMR (CD3COCD3) δ 171.48,
154.64, 139.36, 139.33, 129.06, 128.64, 128.55, 128.54, 127.45, 100.83, 82.59, 66.20, 34.76, 27.46,
23.95, 23.86; ESI-MS (m/z): 404 [M + H]+. HRMS (ESI) m/z calcd. for C21H25NO5SNa [M + Na]+:
426.1351, found 426.1339.
2,2-Dimethyl-3-(4-fluoro)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12f). Yield 81%
1
(135 mg); H-NMR (CD3COCD3): δ 1.73 (s, 3H, i-Pr), 1.84 (s, 3H, i-Pr), 4.58 (d, 1H, J = 5.2 Hz,
2-CH), 5.23 (d, 1H, J = 5.2 Hz, 3-CH), 7.12 (t, 2H, J = 8.8 Hz, PhSO2), 7.22 (m, 3H, 3-Ph), 7.28 (m,
13
2H, 3-Ph), 7.63 (m, 2H, PhSO2); C-NMR (CD3COCD3) δ 171.45, 166.83, 164.32, 139.32, 138.29,
138.26, 131.43, 131.33, 129.16, 128.76, 128.62, 116.60, 116.38, 100.93, 82.50, 66.12, 27.47; ESI-MS
(m/z): 380 [M + H]+. HRMS (ESI) m/z calcd. for C18H18FNO5SNa [M + Na]+: 402.0787, found 402.0782.

Molecules 2013, 18
10199
2,2-Dimethyl-3-(4-trifluoromethyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12g).
1
Yield 78% (147 mg); H-NMR (CD3COCD3): δ 1.77 (s, 3H, i-Pr), 1.88 (s, 3H, i-Pr), 4.64 (d, 1H,
J = 5.2 Hz, 2-CH), 5.29 (d, 1H, J = 4.8 Hz, 3-CH), 7.21 (m, 3H, 3-Ph), 7.30 (m, 2H, 3-Ph), 7.81 (d,
13
2H, J = 8.8 Hz, PhSO2), 8.18 (d, 2H, J = 9.2 Hz, PhSO2); C-NMR (CD3COCD3) δ 171.32, 150.62,
147.27, 138.73, 129.82, 129.28, 128.99, 128.89, 124.68, 101.26, 82.38, 66.18, 27.83; ESI-MS (m/z):
430 [M + H]+. HRMS (ESI) m/z calcd. for C19H18F3NO5SNa [M + Na]+: 452.0755, found 452.0737.
2,2-Dimethyl-3-(4-chloro)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12h). Yield 100%
1
(173 mg); H-NMR (CD3COCD3): δ 1.73 (s, 3H, i-Pr), 1.84 (s, 3H, i-Pr), 4.59 (d, 1H, J = 5.2 Hz,
2-CH), 5.24 (d, 1H, J = 4.8 Hz, 3-CH), 7.23 (m, 3H, 3-Ph), 7.29 (m, 2H, 3-Ph), 7.39 (d, 2H, J = 8.8 Hz,
13
PhSO2), 7.56 (d, 2H, J = 8.0 Hz, PhSO2); C-NMR (CD3COCD3) δ 171.40, 140.74, 139.26, 139.04,
130.14, 129.66, 129.19, 128.76, 128.67, 100.95, 82.46, 66.14, 27.54; ESI-MS (m/z): 396 [M + H]+.
HRMS (ESI) m/z calcd. for C18H18ClNO5SNa [M + Na]+: 418.0492, found 418.0504.
2,2-Dimethyl-3-(4-bromo)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12i). Yield 99%
1
(191 mg); H-NMR (CD3COCD3): δ 1.73 (s, 3H, i-Pr), 1.84 (s, 3H, i-Pr), 4.59 (d, 1H, J = 4.8 Hz,
2-CH), 5.23 (d, 1H, J = 5.2 Hz, 3-CH), 7.23 (m, 3H, 3-Ph), 7.29 (m, 2H, 3-Ph), 7.48 (d, 2H, J = 8.8 Hz,
13
PhSO2), 7.55 (d, 2H, J = 8.8 Hz, PhSO2); C-NMR (CD3COCD3) δ 171.40, 141.20, 139.22, 132.67,
130.20, 129.20, 128.73, 128.70, 127.62, 100.93, 82.45, 66.14, 27.54; ESI-MS (m/z): 439 [M + H]+.
HRMS (ESI) m/z calcd. for C18H18BrNO5SNa [M + Na]+: 461.9987, found 461.9997.
2,2-Dimethyl-3-(2,4,6-trimethyl)benzenesulfonyl-4-phenyl-oxazolidine-5-carboxylic acid (12j). Yield
1
99% (175 mg); H-NMR (CD3COCD3): δ 1.85 (s, 3H, i-Pr), 1.93 (s, 3H, i-Pr), 2.09 (s, 3H, CH3 in
PhSO2), 2.52 (s, 6H, CH3 in PhSO2), 4.44 (d, 1H, J = 5.6 Hz, 2-CH), 5.02 (d, 1H, J = 5.6 Hz, 3-CH),
13
6.63 (s, 2H, PhSO2), 7.01 (m, 5H, 3-Ph); C-NMR (CD3COCD3) δ 171.58, 143.99, 140.68, 138.84,
134.01, 132.52, 128.65, 128.15, 127.39, 102.05, 83.10, 66.04, 27.20, 23.21, 20.68. ESI-MS (m/z): 404
[M + H]+. HRMS (ESI) m/z calcd for C21H25NO5SNa [M + Na]+: 426.1351, found 426.1345.
3.2.4. General Procedure for the Synthesis of 13a–j
To a solution of anhydrous toluene (60 mL) were added 12a–j (0.49 mmol), 7,10-ditroc-10-DAB
(0.23 g, 0.24 mmol), DCC (0.15 g, 0.75 mmol) and DMAP (15 mg, 0.13 mmol). The resulting mixture
was stirred at 85 °C for 3 h. After the completion, the reaction mixture was washed with brine
(30 mL × 3), dried over Na2SO4, filtered and concentrated in vacuo. The obtained residue was purified by
silica gel flash chromatography column (petroleum ether/ethyl acetate: 4/1) to afford 13a–j as white solids.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-benzene sulfonyl-
1
4-phenyl-oxazolidine-5-carboxylate] (13a). Yield 96% (285 mg); mp 155–157 °C; H-NMR (CDCl3):
δ 1.17 (s, 3H, 17-CH3), 1.24 (s, 3H, 16-CH3), 1.82 and 1.87 (2s, 6H, i-Pr), 1.95 (s, 3H, 19-CH3), 1.97
(s, 3H, 18-CH3), 1.99 (s, 3H, OAc), 2.13 (m, 2H, 14-CH2), 2.03 and 2.59 (2m, 2H, 6-CH2), 3.87 (d,
1H, J = 7.2 Hz, 3-CH), 4.11 and 4.27 (2d, 2H, J = 8.6 Hz, 20-CH2), 4.50 (d, 1H, J = 6.0 Hz, 2′-CH),
4.60 and 4.91 (2d, 2H, J = 12.0 Hz, Troc), 4.78 (s, 2H, Troc), 4.90 (d, 1H, J = 7.6 Hz, 5-CH), 5.23
(d, 1H, J = 6.4 Hz, 3′-CH), 5.56 (dd, 1H, J = 10.8, 7.2 Hz, 7-CH), 5.65 (d, 1H, J = 7.2 Hz, 2-CH), 6.21

Molecules 2013, 18
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(t, 1H, J = 8.4 Hz, 13-CH), 6.23 (s, 1H, 10-CH), 7.15 (m, 2H, 3′-Ph), 7.21 (m, 3H, 3′-Ph), 7.26 (t, 2H,
J = 7.6 Hz, m-PhSO2), 7.41 (t, 1H, J = 7.6 Hz, p-PhSO2), 7.46 (d, 2H, J = 7.2 Hz, o-PhSO2), 7.47
(t, 2H, J = 7.6 Hz, m-OBz), 7.62 (t, 1H, J = 7.6 Hz, p-OBz), 8.01 (d, 2H, J = 7.2 Hz, o-OBz).
13C-NMR (CDCl3) δ 200.65, 170.14, 169.78, 166.84, 153.21, 142.48, 140.58, 136.95, 133.87, 132.41,
132.02, 130.05, 129.00, 128.67, 128.58, 128.46, 128.33, 128.00, 127.50, 100.95, 94.19, 83.68, 81.99,
80.43, 79.01, 78.88, 74.23, 71.49, 65.27, 58.46, 56.09, 49.21, 46.90, 43.07, 35.38, 33.91, 33.17, 28.73,
27.18, 26.23, 25.60, 24.92, 21.58, 21.03, 18.43, 14.81, 10.72. Anal. calcd. for C53H55Cl6NO18S: C,
51.39; H, 4.48; N, 1.13. Found: C, 51.52; H, 4.51; N, 1.15.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-phenyl methane
1
sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13b). Yield 94% (282 mg); mp 154–156 °C; H-NMR
(CDCl3): δ 1.20 (s, 3H, 17-CH3), 1.28 (s, 3H, 16-CH3), 1.61 (s, 3H, 19-CH3), 1.84 and 1.85 (2s, 6H,
i-Pr), 2.08 (s, 3H, 18-CH3), 2.10 (s, 3H, OAc), 2.22 (m, 2H, 14-CH2), 2.04 and 2.62 (2m, 2H, 6-CH2),
3.73 (2d, 2H, J = 13.6 Hz, 3″-CH2), 3.93 (d, 1H, J = 7.2 Hz, 3-CH), 4.15 and 4.32 (2d, 2H, J = 8.4 Hz,
20-CH2), 4.70 (d, 1H, J = 5.2 Hz, 2′-CH), 4.62 and 4.94 (2d, 2H, J = 12.0 Hz, Troc), 4.80 (dd, 2H,
J = 12.8, 12.0 Hz, Troc), 4.94 (d, 1H, J = 9.2 Hz, 5-CH), 5.29 (d, 1H, J = 5.2 Hz, 3′-CH), 5.61 (dd, 1H,
J = 10.6, 7.0 Hz, 2-CH), 5.69 (d, 1H, J = 7.2 Hz, 2-CH), 6.27 (t, 1H, J = 8.6 Hz, 13-CH), 6.27 (s, 1H,
10-CH), 7.21 (m, 2H, 3′-Ph), 7.35 (m, 3H, 3′-Ph), 751 (t, 2H, J = 8.0 Hz, m-OBz), 7.51 (m, 2H, 3″-Ph),
7.56 (m, 2H, 3″-Ph), 7.65 (t, 1H, J = 7.6 Hz, p-OBz), 8.05 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR
(CDCl3) δ 200.67, 171.18, 170.18, 170.04, 166.86, 153.22, 153.19, 142.43, 138.48, 133.91, 132.07,
130.99, 130.07, 129.21, 129.14, 128.99, 128.80, 128.71, 128.59, 128.50, 128.17, 100.50, 94.19, 83.70,
81.67, 80.48, 79.02, 78.91, 74.24, 71.66, 64.89, 61.36, 60.41, 56.10, 49.31, 46.94, 43.10, 35.45, 33.83,
33.19, 29.70, 27.98, 27.77, 26.23, 25.57, 24.89, 2, 21.65, 21.06, 21.03, 14.96, 14.21, 10.74. Anal. calcd.
for C54H57Cl6NO18S: C, 51.77; H, 4.59; N, 1.12. Found: C, 51.88; H, 4.65; N, 1.18.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-(4-methyl) benzene
1
sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13c). Yield 85% (255 mg); mp 154–156 °C; H-NMR
(CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.27 (s, 3H, 16-CH3), 1.84 and 1,87 (2s, 6H, i-Pr), 1.94 (s, 3H,
19-CH3), 1.99 (s, 3H, 18-CH3), 2.00 (s, 3H, OAc), 2.16 (m, 2H, 14-CH2), 2.36 (s, 3H, 4″-CH3), 2.05
and 2.61 (2m, 2H, 6-CH2), 3.89 (d, 1H, J = 6.8 Hz, 3-CH), 4.13 and 4.29 (2d, 2H, J = 8.4 Hz, 20-CH2),
4.52 (d, 1H, J = 6.8 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 12.0 Hz, Troc), 4.80 (dd, 2H, J = 14.4, 12.0 Hz,
Troc), 4.92 (d, 1H, J = 7.6 Hz, 5-CH), 5.21 (d, 1H, J = 6.8 Hz, 3′-CH), 5.58 (dd, 1H, J = 10.8, 7.2 Hz,
7-CH), 5.67 (d, 1H, J = 7.2 Hz, 2-CH), 6.22 (t, 1H, J = 8.8 Hz, 13-CH), 6.25 (s, 1H, 10-CH), 7.07 (d,
2H, J = 8.4 Hz, m-PhSO2), 7.20 (m, 2H, 3′-Ph), 7.26 (m, 3H, 3′-Ph), 7.39 (d, 2H, J = 8.4 Hz, o-PhSO2),
7.50 (t, 2H, J = 7.6 Hz, m-OBz), 7.65 (t, 1H, J = 7.4 Hz, p-OBz), 8.04 (d, 2H, J = 7.6 Hz, o-OBz).
13C-NMR (CDCl3) δ 200.65, 171.15, 169.81, 166.85, 153.21, 153.20, 143.32, 142.51, 137.57, 133.88,
131.99, 130.06, 129.10, 128.99, 130.06, 129.10, 128.99, 128.68, 128.53, 128.16, 127.92, 100.81,
94.21, 94.19, 83.67, 81.94, 80.42, 79.02, 78.90, 74.23, 71.45, 65.33, 60.39, 56.08, 46.90, 43.07, 35.37,
33.10, 33.17, 29.70, 28.90, 26.99, 26.23, 25.51, 24.82, 21.57, 21.44, 21.03, 14.78, 14.20, 10.72. Anal.
calcd. for C54H57Cl6NO18S: C, 51.77; H, 4.59; N, 1.12. Found: C, 51.93; H, 4.63; N, 1.16.

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7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-(4-methoxy)
benzene sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13d). Yield 95% (288 mg); mp 159–161 °C;
1H-NMR (CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.26 (s, 3H, 16-CH3), 1.83 and 1.87 (2s, 6H, i-Pr), 1.94 (s,
3H, 19-CH3), 1.99 (s, 3H, 18-CH3), 2.01 (s, 3H, OAc), 2.15 (m, 2H, 14-CH2), 2.05 and 2.61 (2m, 2H,
6-CH2), 3.82 (s, 3H, OCH3), 3.89 (d, 1H, J = 6.8 Hz, 3-CH), 4.13 and 4.28 (2d, 2H, J = 8.4 Hz,
20-CH2), 4.51 (d, 1H, J = 6.8 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 11.6 Hz, Troc), 4.80 (dd, 2H,
J = 14.0, 12.0 Hz, Troc), 4.92 (d, 1H, J = 8.0 Hz, 5-CH), 5.20 (d, 1H, J = 6.4 Hz, 3′-CH), 5.58 (dd,
J = 10.8, 7.2 Hz, 7-CH), 5.67 (d, 1H, J = 7.6 Hz, 2-CH), 6.22 (t, 1H, J = 9.2 Hz, 13-CH), 6.25 (s, 1H,
10-CH), 6.72 (d, 2H, J = 8.8 Hz, o-3″-PhOCH3), 7.23 (m, 5H, 3′-Ph), 7.41 (d, J = 9.2 Hz,
m-3″-PhOCH3), 7.50 (t, 2H, J = 7.6 Hz, m-OBz), 7.64 (t, 1H, J = 7.6 Hz, p-OBz), 8.03 (d, 2H, J = 7.6 Hz,
o-OBz). 13C-NMR (CDCl3) δ 200.66, 171.15, 170.16, 169.86, 166.82, 162.70, 153.21, 153.19, 142.51,
137.31, 133.87, 132.00, 132.19, 132.00, 130.05, 129.75, 129.01, 128.67, 128.55, 128.20, 127.93,
113.64, 100.84, 94.21, 94.19, 83.67, 81.98, 80.41, 79.02, 78.88, 74.24, 71.45, 65.28, 60.39, 56.08, 55.58,
49.23, 46.90, 43.07, 35.39, 33.86, 33.17, 28.89, 26.96, 26.23, 25.59, 24.90, 21.57, 21.04, 14.80, 14.20,
10.72. Anal. calcd. for C54H57Cl6NO19S: C, 51.12; H, 4.53; N, 1.10. Found: C, 51.33; H, 4.55; N, 1.14.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-(4-isopropyl)
benzene sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13e). Yield 87% (267 mg); mp 165–167 °C;
1H-NMR (CDCl3): δ 1.18 (s, 3H, 17-CH3), 1.22 (d, 3H, J = 1.6 Hz, 2″-CH3), 1.24 (d, 3H, J = 1.6 Hz,
2″-CH3), 1.26 (s, 3H, 16-CH3), 1.83 and 1.89 (2s, 6H, i-Pr), 1.96 (s, 3H, 19-CH3), 1.99 (s, 3H,
18-CH3), 2.00 (s, 3H, OAc), 2.15 (m, 2H, 14-CH2), 2.05 and 2.61 (2m, 2H, 6-CH2), 2.89 (m, 1H,
2″-CH), 3.89 (d, 1H, J = 7.2 Hz, 3-CH), 4.12 and 4.28 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.51 (d, 1H,
J = 6.4 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 12.0 Hz, Troc), 4.80 (dd, 2H, J = 14.4, 12.0 Hz, Troc),
4.92 (d, 1H, J = 8.0 Hz, 5-CH), 5.24 (m, 1H, 3′-CH), 5.58 (dd, 1H, J = 10.8, 7.2 Hz, 7-CH), 5.66 (d,
1H, J = 7.2 Hz, 2-CH), 6.22 (t, 1H, J = 9.2 Hz, 13-CH), 6.24 (s, 1H, 10-CH), 7.08 (d, 2H, J = 8.0 Hz,
3″-Ph), 7.14 (m, 2H, 3′-Ph), 7.20 (m, 3H, 3′-Ph), 7.39 (d, 2H, J = 8.8 Hz, 3″-Ph), 7.49 (t, 2H, J = 7.6 Hz,
m-OBz), 7.64 (t, 1H, J = 7.6 Hz, p-OBz), 8.03 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR (CDCl3) δ 200.66,
171.15, 170.15, 169.88, 166.82, 153.91, 153.20, 153.19, 142.51, 137.01, 133.87, 131.99, 130.05,
129.01, 128.67, 128.47, 128.18, 127.97, 127.73, 126.52, 100.94, 94.22, 94.20, 83.67, 82.01, 80.41,
79.01, 78.88, 74.24, 71.46, 65.30, 60.39, 56.07, 53.43, 46.89, 43.07, 35.39, 34.09, 33.16, 28.82, 27.06,
26.23, 23.67, 23.58, 21.55, 21.03, 14.81, 14.20, 10.72. Anal. calcd. for C56H61Cl6NO18S: C, 52.51; H,
4.80; N, 1.09. Found: C, 52.75; H, 4.88; N, 1.15.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-(4-fluoro) benzene
1
sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13f). Yield 89% (268 mg); mp 166–168 °C; H-NMR
(CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.27 (s, 3H, 16-CH3), 1.84 and 1.90 (2s, 6H, i-Pr), 1.97 (s, 3H,
19-CH3), 2.01 (s, 3H, 18-CH3), 2.04 (s, 3H, OAc), 2.16 (m, 2H, 14-CH2), 2.05 and 2.62 (2m, 2H,
6-CH2), 3.90 (d, 1H, J = 6.8 Hz, 3-CH), 4.13 and 4.29 (2d, 2H, J = 8.8 Hz, 20-CH2), 4.52 (d, 1H,
J = 6.4 Hz, 2′-CH), 4.62 and 4.94 (2d, 2H, J = 11.6 Hz, Troc), 4.80 (dd, 2H, J = 13.0, 11.8 Hz, Troc),
4.93 (d, 1H, J = 9.2 Hz, 5-CH), 5.25 (d, 1H, J = 6.4 Hz, 3′-CH), 5.59 (dd, 1H, J = 10.8, 7.2 Hz, 5-CH),
5.67 (d, 1H, J = 7.2 Hz, 2-CH), 6.24 (t, 1H, J = 8.4 Hz, 13-CH), 6.25 (s, 1H, 10-CH), 6.90 (t, 2H,
J = 8.4 Hz, -PhF), 7.20 (m, 4H, 3′-Ph), 7.26 (m, 1H, 3′-Ph), 7.45 (m, 2H, -PhF), 7.49 (t, 2H, J = 7.6 Hz,

Molecules 2013, 18
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m-OBz), 7.64 (t, 1H, J = 7.6 Hz, p-OBz), 8.03 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR (CDCl3) δ
200.65, 171.17, 170.13, 169.77, 166.84, 166.02, 163.49, 153.21, 142.42, 136.71, 133.90, 132.05,
130.30, 130.20, 130.05, 128.97, 128.68, 128.65, 128.46, 128.11, 115.70, 115.47, 101.12, 94.18, 83.68,
82.03, 80.44, 79.00, 78.89, 74.21, 71.55, 65.15, 60.40, 56.08, 46.91, 43.07, 35.36, 33.17, 28.59, 27.26,
26.22, 21.59, 21.06, 21.02, 14.85, 14.21, 10.73. Anal. calcd. for C53H54Cl6FNO18S: C, 50.65; H, 4.33;
N, 1.11. Found: C, 50.82; H, 4.37; N, 1.18.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-(4-trifluoro methyl)
benzene sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13g). Yield 100% (312 mg); mp 165–167 °C;
1H-NMR (CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.27 (s, 3H, 16-CH3), 1.84 and 1.92 (2s, 6H, i-Pr), 1.99 (s,
3H, 19-CH3), 2.02 (s, 3H, 18-CH3), 2.03 (s, 3H, OAc), 2.16 (m, 2H, 14-CH2), 2.05 and 2.62 (2m, 2H,
6-CH2), 3.90 (d, 1H, J = 6.8 Hz, 3-CH), 4.13 and 4.29 (2d, 2H, J = 8.0 Hz, 20-CH2), 4.54 (d, 1H,
J = 6.4 Hz, 2′-CH), 4.63 and 4.94 (2d, 2H, J = 12.0 Hz, Troc), 4.80 (dd, 2H, J = 13.6, 12.0 Hz, Troc),
4.93 (d, 1H, J = 7.6 Hz, 5-CH), 5.29 (dd, 1H, J = 6.0 Hz, 3′-CH), 5.59 (dd, 1H, J = 10.8, 6.8 Hz,
7-CH), 5.67 (d, 1H, J = 6.8 Hz, 2-CH), 6.24 (t, 1H, J = 9.2 Hz, 13-CH), 6.26 (s, 1H, 10-CH), 7.14 (m,
1H, 3′-Ph), 7.23 (m, 4H, 3′-Ph), 7.47 (d, 2H, J = 8.4 Hz, -PhCF3), 7.53 (d, 2H, J = 8.4 Hz, -PhCF3),
7.49 (t, 2H, J = 8.0 Hz, m-OBz), 7.37 (t, 1H, J = 7.6 Hz, p-OBz), 8.02 (d, 2H, J = 7.6 Hz, o-OBz).
13C-NMR (CDCl3) δ 200.64, 171.17, 170.10, 169.66, 166.84, 153.21, 144.07, 142.32, 136.19, 134.04,
133.90, 133.71, 132.11, 130.05, 128.96, 128.68, 128.60, 127.94, 125.49, 125.45, 124.47, 121.76,
101.32, 94.18, 83.67, 82.00, 80.46, 78.98, 74.20, 71.62, 65.16, 60.40, 56.08, 46.92, 43.08, 35.36,
33.17, 28.42, 27.55, 26.22, 21.60, 21.06, 21.00, 14.85, 14.20, 10.72. Anal. calcd. for
C54H54Cl6F3NO18S: C, 49.63; H, 4.17; N, 1.07. Found: C, 49.85; H, 4.22; N, 1.13.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin
III-13-O-[2,2-dimethyl-3-(4-chloro)
benzene sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13h). Yield 91% (277 mg); mp 169–171 °C;
1H-NMR (CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.27 (s, 3H, 16-CH3), 1.84 and 1.89 (2s, 6H, i-Pr), 1.96 (s,
3H, 19-CH3), 2.01 (s, 3H, 18-CH3), 2.03 (s, 3H, OAc), 2.16 (m, 2H, 14-CH2), 2.05 and 2.61 (2m, 2H,
6-CH2), 3.90 (d, 1H, J = 7.2 Hz, 3-CH), 413 and 4.29 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.53 (d, 1H,
J = 6.4 Hz, 2′-CH), 4.62 and 4.94 (2d, 2H, J = 11.6 Hz, Troc), 4.80 (dd, 2H, J = 13.6, 11.6 Hz, Troc),
4.93 (d, 1H, J = 8.0 Hz, 5-CH), 5.25 (d, 1H, J = 6.4 Hz, 3′-CH), 5.58 (dd, 1H, J = 10.8, 7.2 Hz, 2-CH),
5.67 (d, 1H, J = 7.2 Hz, 2-CH), 6.24 (t, 1H, J = 9.2 Hz, 13-CH), 6.25 (s, 1H, 10-CH), 7.20 (d, 2H,
J = 9.2 Hz, -PhCl), 7.20 (m, 4H, 3′-Ph), 7.28 (m, 1H, 3′-Ph), 7.36 (d, 2H, J = 8.8 Hz, -PhCl), 7.49
(t, 2H, J = 7.6 Hz, m-OBz), 7.64 (t, 1H, J = 7.6 Hz, p-OBz), 8.03 (d, 2H, J = 7.6 Hz, o-OBz).
13C-NMR (CDCl3) δ 200.65, 171.18, 170.13, 169.73, 166.84, 153.21, 142.40, 139.11, 138.95, 136.66,
133.90, 138.95, 136.66, 133.90, 132.06, 130.05, 128.97, 128.92, 128.68, 128.46, 128.14, 101.10,
94.20, 94.18, 83.67, 81.98, 80.44, 78.99, 78.89, 74.21, 71.55, 65.18, 60.41, 56.08, 46.91, 43.07, 35.37,
33.17, 28.58, 27.31, 26.23, 21.60, 21.06, 21.02, 14.84, 14.21, 10.73. Anal. calcd. for C53H54Cl7NO18S:
C, 50.00; H, 4.27; N, 1.10. Found: C, 50.23; H, 4.34; N, 1.15.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin
III-13-O-[2,2-dimethyl-3-(4-bromo)
benzene sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13i). Yield 98% (309 mg); mp 166–168 °C;
1H-NMR (CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.27 (s, 3H, 16-CH3), 1.84 and 1.89 (2s, 6H, i-Pr), 1.96 (s,

Molecules 2013, 18
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3H, 19-CH3), 2.01 (s, 3H, 18-CH3), 2.03 (s, 3H, OAc), 2.16 (m, 2H, 14-CH2), 2.06 and 2.62 (2m, 2H,
6-CH2), 3.90 (d, 1H, J = 6.8 Hz, 3-CH), 4.13 and 4.29 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.53 (d, 1H,
J = 6.0 Hz, 2′-CH), 4.62 and 4.94 (2d, 2H, J = 11.8 Hz, Troc), 4.80 (dd, 2H, J = 13.8, 11.8 Hz, Troc),
4.93 (d, 1H, J = 8.0 Hz, 5-CH), 5.25 (d, 1H, J = 6.0 Hz, 3′-CH), 5.59 (dd, 1H, J = 10.8, 7.2 Hz, 7-CH),
5.67 (d, 1H, J = 7.2 Hz, 2-CH), 6.24 (t, 1H, J = 9.2 Hz, 13-CH), 6.25 (s, 1H, 10-CH), 7.20 (m, 4H,
3′-Ph), 7.28 (m, 1H, 3′-Ph), 7.29 (d, 2H, J = 8.8 Hz, -PhBr), 7.37 (d, 2H, J = 8.8 Hz, -PhBr), 7.50 (t,
2H, J = 7.8 Hz, m-OBz), 7.64 (t, 1H, J = 7.4 Hz, p-OBz), 8.03 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR
(CDCl3) δ 200.65, 170.12, 169.73, 166.85, 153.21, 142.39, 139.64, 136.63, 133.90, 132.06, 131.66,
130.06, 129.00, 128.96, 128.71, 128.46, 128.13, 127.49, 101.10, 94.18, 83.67, 81.97, 80.44, 78.99,
78.90, 74.20, 71.56, 65.20, 60.41, 56.08, 46.91, 43.08, 35.36, 33.17, 28.58, 27.32, 26.23, 21.60, 21.01,
14.84, 14.21, 10.73. Anal. calcd. for C53H54BrCl6NO18S: C, 48.31; H, 4.13; N, 1.06. Found: C, 48.53;
H, 4.23; N, 1.14.
7,10-Di(2,2,2-trichloroethyloxycarbonyl)-10-deacetylbaccatin III-13-O-[2,2-dimethyl-3-(2,4,6-trimethyl)
benzene sulfonyl-4-phenyl-oxazolidine-5-carboxylate] (13j). Yield 81% (248 mg); mp 167–169 °C;
1H-NMR (CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.28 (s, 3H, 16-CH3), 1.84 and 1.96 (2s, 6H, i-Pr), 1.98 (s,
3H, 19-CH3), 2.03 (s, 3H, 18-CH3), 2.08 (s, 3H, OAc), 2.12 (s, 3H, p-3″-CH3), 2.14 (m, 2H, 14-CH2),
2.05 and 2.62 (2m, 2H, 6-CH2), 2.54 (s, 6H, o-3″-CH3), 3.91 (d, 1H, J = 7.2 Hz, 3-CH), 4.13 and 4.28
(2d, 2H, J = 8.4 Hz, 20-CH2), 4.44 (d, 1H, J = 6.8 Hz, 2′-CH), 4.63 and 4.94 (2d, 2H, J = 11.8 Hz,
Troc), 4.80 (s, 2H, Troc), 4.93 (d, 1H, J = 8.0 Hz, 5-CH), 5.15 (d, 1H, J = 6.8 Hz, 3′-CH), 5.59 (dd,
1H, J = 10.8, 7.2 Hz, 7-CH), 5.67 (d, 1H, J = 7.2 Hz, 2-CH), 6.27 (t, 1H, J = 8.2 Hz, 13-CH), 6.27 (s,
1H, 10-CH), 6.55 (s, 2H, 3″-Ph), 6.95–7.09 (m, 5H, 3′-Ph), 7.49 (t, 2H, J = 7.8 Hz, m-OBz), 7.63 (t,
1H, J = 7.6 Hz, p-OBz), 8.02 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR (CDCl3) δ 200.72, 171.18, 170.17,
170.09, 166.83, 153.21, 153.19, 143.12, 142.62, 140.07, 136.70, 133.85, 132.93, 131.91, 131.69,
130.07, 129.00, 128.65, 128.00, 127.66, 126.91, 102.19, 94.20, 83.70, 82.46, 80.38, 79.02, 78.94,
74.23, 71.45, 65.32, 60.41, 56.06, 46.90, 43.06, 35.38, 33.17, 29.70, 29.05, 26.89, 26.33, 23.04, 21.53,
21.04, 20.72, 14.90, 14.21, 10.73. Anal. calcd. for C56H61Cl6NO18S: C, 52.51; H, 4.80; N, 1.09. Found:
C, 52.75; H, 4.88; N, 1.17.
3.2.5. General Procedure for the Synthesis of 5a–j
To a round-bottomed flask (25 mL) were added 13a–j (0.218 mmol) and HCOOH (>98%, 5 mL).
The reaction mixture was stirred at room temperature for 4 h. Then the resulting solution was
neutralized by addition of saturated NaHCO3. After extracted with EtOAc three times, the combined
organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. The obtained
residue was purified by silica gel flash chromatography column (acetone/petroleum ether: 1/3) to afford
5a–j as white solids.
N-De-tert-butoxycarbonyl-N-phenylsulfonyl 7,10-di(2,2,2-trichloroethyloxycarbonyl)-docetaxel (5a).
Yield 72% (188 mg); mp 156–158 °C; 1H-NMR (CDCl3): δ 1.19 (s, 3H, 17-CH3), 1.25 (s, 3H, 16-CH3),
1.86 (s, 3H, 19-CH3), 1.90 (s, 3H, 18-CH3), 2.25 (m, 2H, 14-CH2), 2.34 (s, 3H, OAc), 2.06 and 2.61
(2m, 2H, 6-CH2), 3.86 (d, 1H, J = 6.8 Hz, 3-CH), 4.20 and 4.31 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.54 (d,
1H, J = 3.2 Hz, 2′-CH), 4.60 and 4.91 (2d, 2H, J = 12.0 Hz, Troc), 4.78 (s, 2H, Troc), 4.93 (d, 1H,

Molecules 2013, 18
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J = 9.6 Hz, 5-CH), 4.93 (m, 1H, 3′-CH), 5.52 (m, 1H, 7-CH), 5.67 (d, 1H, J = 6.8 Hz, 2-CH), 5.79 (m,
1H, -CONH-), 6.16 (t, 1H, J = 8.8 Hz, 13-CH), 6.21 (s, 1H, 10-CH), 7.09 (m, 2H, 3′-Ph), 7.18 (m, 3H,
3′-Ph), 7.28 (t, 2H, J = 8.0 Hz, m-PhSO2), 7.42 (t, 1H, J = 7.6 Hz, p-PhSO2), 7.48 (t, 2H, J = 7.6 Hz,
m-OBz), 7.61 (t, 1H, J = 7.6 Hz, p-OBz), 7.62 (d, 2H, J = 7.6 Hz, o-PhSO2), 8.08 (d, 2H, J = 7.6 Hz,
o-OBz). 13C-NMR (CDCl3) δ 200.62, 170.61, 166.78, 153.22, 142.02, 140.18, 136.31, 133.88, 132.62,
132.30, 130.13, 129.04, 128.81, 128.72, 128.65, 128.36, 127.05, 126.91, 94.17, 83.60, 80.95, 79.12,
78.61, 74.62, 74.12, 72.10, 60.42, 59.50, 56.27, 46.92, 43.02, 35.53, 33.28, 26.50, 22.46, 20.73, 14.91,
14.20, 10.73. Anal. calcd. for C50H51Cl6NO18S: C, 50.10; H, 4.29; N, 1.17. Found: C, 50.33; H, 4.43;
N, 1.23.
N-De-tert-butoxycarbonyl-N-phenylmethylsulfonyl 7,10-di(2,2,2-trichloroethyloxycarbonyl)-docetaxel
1
(5b). Yield 79% (208 mg); mp 149–151 °C; H-NMR (CDCl3): δ 1.20 (s, 3H, 17-CH3), 1.27 (s, 3H,
16-CH3), 1.76 (s, 3H, 19-CH3), 1.91 (s, 3H, 18-CH3), 2.29 (m, 2H, 14-CH2), 2.35 (s, 3H, OAc), 2.07
and 2.62 (2m, 2H, 6-CH2), 3.89 (d, 1H, J = 7.2 Hz, 3-CH), 4.04 (s, 2H, 3″-CH2), 4.22 and 4.32 (2d,
2H, J = 8.6 Hz, 20-CH2), 4.54 (br s, 1H, 2′-CH), 4.61 and 4.92 (2d, 2H, J = 11.6 Hz, Troc), 4.79 (s,
2H, Troc), 4.88 (m, 1H, 3′-CH), 4.95 (d, 1H, J = 9.2 Hz, 5-CH), 5.53 (dd, 1H, J = 10.8, 7.2 Hz, 2-CH),
5.69 (d, 1H, J = 7.2 Hz, 2-CH), 6.22 (s, 1H, 10-CH), 6.25 (t, 1H, J = 8.0 Hz, 13-CH), 7.07 (d, 2H,
J = 7.2 Hz, 3″-Ph), 7.22 (t, 2H, J = 7.2 Hz, 3′-Ph), 7.35 (d, 2H, J = 7.6 Hz, 3″-Ph), 7.42 (m, 3H, 3′-Ph),
7.48 (t, 2H, J = 8.0 Hz, m-OBz), 7.63 (t, 1H, J = 7.4 Hz, p-OBz), 8.10 (d, 2H, J = 7.6 Hz, o-OBz).
13C-NMR (CDCl3) δ 200.65, 171.53, 170.52, 166.75, 153.22, 153.17, 142.17, 137.52, 133.82, 132.20,
130.71, 130.16, 129.08, 129.02, 128.83, 128.68, 128.59, 128.44, 127.48, 94.18, 83.62, 80.89, 79.12,
78.61, 74.68, 74.19, 72.15, 60.41, 60.25, 59.57, 58.47, 56.24, 46.87, 43.04, 35.54, 33.81, 33.26, 29.69,
26.45, 25.57, 24.89, 22.47, 21.05, 20.84, 18.40, 14.79, 14.20, 10.73. Anal. calcd. for C51H53Cl6NO18S:
C, 50.51; H, 4.40; N, 1.15. Found: C, 50.73; H, 4.53; N, 1.16.
N-De-tert-butoxycarbonyl-N-(4-methyl)-phenylsulfonyl 7,10-di(2,2,2-trichloroethyloxycarbonyl)-docetaxel
1
(5c). Yield 85% (224 mg); mp 157–159 °C; H-NMR (CDCl3): δ 1.20 (s, 3H, 17-CH3), 1.26 (s, 3H,
16-CH3), 1.88 (s, 3H, 19-CH3), 1.91 (s, 3H, 18-CH3), 2.26 (m, 2H, 14-CH2), 2.34 (s, 3H, OAc), 2.35
(s, 3H, CH3 in 4-methylphenyl), 2.08 and 2.63 (2m, 2H, 6-CH2), 3.88 (d, 1H, J = 6.8 Hz, 3-CH), 4.22
and 4.32 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.56 (d, 1H, J = 3.2 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 12.0 Hz,
Troc), 4.80 (s, 2H, Troc), 4.91 (m, 1H, 3′-CH), 4.94 (d, 1H, J = 9.2 Hz, 5-CH), 5.54 (m, 1H, 7-CH),
5.69 (d, 1H, J = 6.8 Hz, 2-CH), 5.84 (m, 1H, -CONH-), 6.18 (t, 1H, J = 9.0 Hz, 13-CH), 6.22 (s, 1H,
10-CH), 7.08 (d, 2H, J = 8.4 Hz, m-PhSO2), 7.13 (m, 2H, 3′-Ph), 7.21 (m, 3H, 3′-Ph), 7.50 (t, 2H,
J = 7.6 Hz, m-OBz), 7.53 (d, 2H, J = 8.4 Hz, o-PhSO2), 7.64 (t, 1H, J = 7.4 Hz, p-OBz), 8.10 (d, 2H,
J = 7.6 Hz, o-OBz). 13C-NMR (CDCl3) δ 200.64, 170.58, 166.78, 153.22, 153.20, 143.51, 142.10,
137.25, 136.58, 133.87, 132.22, 130.14, 129.40, 129.07, 128.72, 128.62, 128.24, 127.08, 126.96, 94.17,
83.61, 80.90, 79.11, 78.63, 74.60, 74.17, 72.06, 59.51, 56.24, 46.90, 43.02, 35.50, 26.44, 22.46, 21.45,
20.79, 14.85, 10.73. Anal. calcd. for C51H53Cl6NO18S: C, 50.51; H, 4.40; N, 1.15. Found: C, 50.75; H,
4.51; N, 1.19.
N-De-tert-butoxycarbonyl-N-(4-methoxyl)-phenylsulfonyl
7,10-di(2,2,2-trichloroethyloxycarbonyl)-
1
docetaxel (5d). Yield 79% (210 mg); mp 152–154 °C; H-NMR (CDCl3): δ 1.21 (s, 3H, 17-CH3),

Molecules 2013, 18
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1.27 (s, 3H, 16-CH3), 1.86 (s, 3H, 19-CH3), 1.92 (s, 3H, 18-CH3), 2.22 (m, 2H, 14-CH2), 2.36 (s, 3H,
OAc), 2.08 and 2.64 (2m, 2H, 6-CH2), 3.80 (s, 3H, OCH3), 3.89 (d, 1H, J = 7.2 Hz, 3-CH), 4.22 and
4.34 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.55 (d, 1H, J = 3.2 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 12.0 Hz,
Troc), 4.80 (s, 2H, Troc), 4.91 (m, 1H, 3′-CH), 4.96 (d, 1H, J = 9.2 Hz, 5-CH), 5.54 (dd, J = 10.8, 7.2 Hz,
7-CH), 5.69 (d, 1H, J = 6.8 Hz, 2-CH), 5.74 (m, 1H, -CONH-), 6.16 (t, 1H, J = 8.8 Hz, 13-CH), 6.23
(s, 1H, 10-CH), 6.76 (m, 2H, o-PhOCH3), 7.15 (m, 2H, 3′-Ph), 7.23 (m, 3H, 3′-Ph), 7.51 (t, 2H,
J = 7.6 Hz, m-OBz), 7.58 (d, 2H, J = 8.8 Hz, m-PhOCH3), 7.64 (t, 1H, J = 7.2 Hz, p-OBz), 8.10 (d, 2H,
J = 7.6 Hz, o-OBz). 13C-NMR (CDCl3) δ 200.64, 171.18, 170.57, 166.77, 162.83, 153.22, 136.72,
133.87, 132.22, 131.87, 130.13, 129.12, 128.72, 128.66, 128.27, 127.09, 113.94, 94.18, 83.60, 80.92,
79.12, 78.62, 74.13, 72.00, 60.40, 56.27, 55.57, 46.91, 43.02, 35.53, 33.80, 33.29, 26.43, 25.56, 24.88,
22.44, 21.05, 20.74, 14.90, 14.20, 10.72. Anal. calcd. for C51H53Cl6NO19S: C, 49.85; H, 4.35; N, 1.14.
Found: C, 49.99, H, 4.43, N, 1.21.
N-De-tert-butoxycarbonyl-N-(4-isopropyl)-phenylsulfonyl
7,10-di(2,2,2-trichloroethyloxycarbonyl)-
1
docetaxel (5e). Yield 77% (208 mg); mp 165–167 °C; H-NMR (CDCl3): δ 1.20 (br s, 6H, 2CH3 in
i-Pr), 1.21 (s, 3H, 17-CH3), 1.27 (s, 3H, 16-CH3), 1.88 (s, 3H, 19-CH3), 1.92 (s, 3H, 18-CH3), 2.29 (m,
2H, 14-CH2), 2.37 (s, 3H, OAc), 2.08 and 2.64 (2m, 2H, 6-CH2), 2.88 (m, 1H, CH in i-Pr), 3.89 (d, 1H,
J = 6.4 Hz, 3-CH), 4.23 and 4.32 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.56 (d, 1H, J = 3.6 Hz, 2′-CH), 4.62
and 4.93 (2d, 2H, J = 11.6 Hz, Troc), 4.80 (s, 2H, Troc), 4.93 (m, 1H, 3′-CH), 4.94 (d, 1H, J = 9.2 Hz,
5-CH), 5.54 (dd, 1H, J = 10.6, 7.4 Hz, 7-CH), 5.70 (d, 1H, J = 6.8 Hz, 2-CH), 6.23 (s, 1H, 10-CH),
6.23 (t, 1H, J = 9.0 Hz, 13-CH), 7.01-7.15 (m, 8H, 3′-Ph and i-PrPh), 7.52 (m, 2H, i-PrPh), 7.52 (t, 2H,
J = 7.6 Hz, m-OBz), 7.63 (t, 1H, J = 7.2 Hz, p-OBz), 8.11 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR (100
MHz, CDCl3) δ 200.65, 171.23, 170.63, 166.74, 154.17, 153.22, 142.15, 137.36, 136.21, 133.82,
132.22, 130.15, 129.13, 128.71, 128.51, 128.21, 127.09, 126.84, 94.18, 83.62, 80.88, 79.12, 78.62,
74.66, 74.21, 72.06, 60.41, 59.63, 56.22, 46.91, 43.02, 35.62, 34.08, 33.27, 26.45, 23.65, 23.60, 22.47,
21.05, 20.87, 14.83, 14.20, 10.75. Anal. calcd. for C53H57Cl6NO18S: C, 51.30; H, 4.63; N, 1.13. Found:
C, 51.53; H, 4.72; N, 1.18.
N-De-tert-butoxycarbonyl-N-(4-fluoro)-phenylsulfonyl 7,10-di(2,2,2-trichloroethyloxycarbonyl)-docetaxel
(5f). Yield 50% (132 mg); mp 162–164 °C;1H-NMR (CDCl3): δ 1.21 (s, 3H, 17-CH3), 1.26 (s, 3H,
16-CH3), 1.88 (s, 3H, 19-CH3), 1.92 (s, 3H, 18-CH3), 2.27 (m, 2H, 14-CH2), 2.36 (s, 3H, OAc), 2.08
and 2.63 (2m, 2H, 6-CH2), 3.88 (d, 1H, J = 6.8 Hz, 3-CH), 4.22 and 4.33 (2d, 2H, J = 8.6 Hz, 20-CH2),
4.56 (d, 1H, J = 3.6 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 11.6 Hz, Troc), 4.80 (s, 2H, Troc), 4.95 (d,
1H, J = 9.6 Hz, 3′-CH), 4.96 (d, 1H, J = 9.2 Hz, 5-CH), 5.53 (dd, 1H, J = 10.6, 7.4 Hz, 5-CH), 5.69 (d,
1H, J = 7.2 Hz, 2-CH), 5.92 (d, 1H, J = 9.2 Hz, -CONH-), 6.20 (t, 1H, J = 8.0 Hz, 13-CH), 6.23 (s, 1H,
10-CH), 6.94 (t, 2H, J = 8.4 Hz, -PhF), 7.11 (m, 2H, 3′-Ph), 7.21 (m, 3H, 3′-Ph), 7.50 (t, 2H, J = 7.6 Hz,
m-OBz), 7.62 (m, 2H, -PhF), 7.63 (t, 1H, J = 7.6 Hz, p-OBz), 8.10 (d, 2H, J = 8.0 Hz, o-OBz).
13C-NMR (CDCl3) δ 200.58, 171.21, 171.08, 170.66, 166.77, 166.16, 163.63, 153.22, 141.91, 136.30,
136.12, 133.90, 132.40, 130.12, 129.71, 129.62, 129.02, 128.71, 128.69, 128.47, 127.13, 126.89,
116.05, 115.82, 94.16, 83.58, 81.01, 79.10, 78.58, 74.62, 74.10, 72.11, 60.42, 59.57, 58.48, 56.29,
46.94, 43.02, 35.51, 33.28, 26.47, 22.45, 21.05, 20.67, 18.41, 14.94, 14.20, 10.72. Anal. calcd. for
C50H50Cl6FNO18S: C, 49.36; H, 4.14; N, 1.15. Found: C, 49.58; H, 4.22; N, 1.16.

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N-De-tert-butoxycarbonyl-N-(4-trifluoromethyl)-phenylsulfonyl 7,10-di(2,2,2-trichloroethyloxy carbonyl)-
docetaxel (5g). Yield 56% (154 mg); mp 159–161 °C; 1H-NMR (CDCl3): δ 1.21 (s, 3H, 17-CH3), 1.27
(s, 3H, 16-CH3), 1.89 (s, 3H, 19-CH3), 1.90 (s, 3H, 18-CH3), 2.29 (m, 2H, 14-CH2), 2.36 (s, 3H, OAc),
2.09 and 2.64 (2m, 2H, 6-CH2), 3.88 (d, 1H, J = 6.8 Hz, 3-CH), 4.23 and 4.33 (2d, 2H, J = 8.6 Hz,
20-CH2), 4.58 (d, 1H, J = 2.4 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 11.6 Hz, Troc), 4.80 (s, 2H, Troc),
4.96 (d, 1H, J = 9.6 Hz, 5-CH), 5.01 (dd, 1H, J = 9.2, 7.2 Hz, 3′-CH), 5.53 (dd, 1H, J = 10.6, 7.4 Hz,
7-CH), 5.69 (d, 1H, J = 7.2 Hz, 2-CH), 6.00 (d, 1H, J = 9.6 Hz, -CONH-), 6.22 (t, 1H, J = 8.2 Hz, 13-CH),
6.23 (s, 1H, 10-CH), 7.07 (m, 2H, 3′-Ph), 7.17 (m, 3H, 3′-Ph), 7.50 (d, 2H, J = 8.4 Hz, -PhCF3),
7.50 (t, 2H, J = 7.6 Hz, m-OBz), 7.64 (t, 1H, J = 7.6 Hz, p-OBz), 7.70 (d, 2H, J = 8.4 Hz, -PhCF3),
8.09 (d, 2H, J = 7.2 Hz, o-OBz). 13C-NMR (CDCl3) δ 200.54, 170.86, 170.76, 166.78, 153.24, 143.76,
141.74, 135.70, 133.93, 132.53, 130.11, 128.98, 128.72, 128.68, 128.54, 127.41, 127.17, 125.79,
94.15, 83.55, 81.10, 79.10, 78.54, 74.57, 74.03, 72.12, 59.60, 58.49, 56.33, 46.97, 43.02, 35.50, 33.30,
26.52, 22.46, 21.05, 20.56, 18.42, 15.00, 14.20, 10.71. Anal. calcd. for C51H50Cl6F3NO18S: C, 48.36; H,
3.98; N, 1.11. Found: C, 48.59; H, 4.11; N, 1.15.
N-De-tert-butoxycarbonyl-N-(4-chloro)-phenylsulfonyl 7,10-di(2,2,2-trichloroethyloxycarbonyl)-docetaxel
1
(5h). Yield 67% (180 mg); mp 162–164 °C; H-NMR (CDCl3): δ 1.21 (s, 3H, 17-CH3), 1.27 (s, 3H,
16-CH3), 1.88 (s, 3H, 19-CH3), 1.90 (s, 3H, 18-CH3), 2.27 (m, 2H, 14-CH2), 2.35 (s, 3H, OAc), 2.08
and 2.64 (2m, 2H, 6-CH2), 3.88 (d, 1H, J = 6.8 Hz, 3-CH), 4.22 and 4.33 (2d, 2H, J = 8.8 Hz, 20-CH2),
4.57 (br s, 1H, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 12.0 Hz, Troc), 4.80 (s, 2H, Troc), 4.96 (d, 1H,
J = 9.6 Hz, 5-CH), 4.97 (d, 1H, J = 9.2 Hz, 3′-CH), 5.53 (dd, 1H, J = 10.4, 7.0 Hz, 2-CH), 5.69 (d, 1H,
J = 7.2 Hz, 2-CH), 5.92 (d, 1H, J = 9.2 Hz, -CONH-), 6.19 (t, 1H, J = 8.8 Hz, 13-CH), 6.23 (s, 1H,
10-CH), 7.12 (m, 2H, -PhCl), 7.23 (m, 5H, 3′-Ph), 7.50 (t, 2H, J = 7.6 Hz, m-OBz), 7.53 (d, 2H,
J = 8.8 Hz, -PhCl), 7.64 (t, 1H, J = 7.6 Hz, p-OBz), 8.09 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR
(CDCl3) δ 200.57, 171.01, 170.68, 166.77, 153.22, 141.85, 139.09, 138.78, 136.12, 133.92, 132.43,
130.12, 129.00, 128.72, 128.48, 128.36, 127.14, 94.17, 83.57, 81.03, 79.10, 78.57, 74.58, 74.07, 72.12,
60.42, 59.55, 56.30, 46.95, 43.02, 35.51, 33.29, 26.49, 22.46, 20.64, 14.95, 14.20, 10.72. Anal. calcd.
for C50H50Cl7NO18S: C, 48.70; H, 4.09; N, 1.14. Found: C, 48.95; H, 4.11; N, 1.18.
N-De-tert-butoxycarbonyl-N-(4-bromo)-phenylsulfonyl 7,10-di(2,2,2-trichloroethyloxycarbonyl)-docetaxel
1
(5i). Yield 57% (158 mg); mp 155–157 °C; H-NMR (CDCl3): δ 1.21 (s, 3H, 17-CH3), 1.27 (s, 3H,
16-CH3), 1.88 (s, 3H, 19-CH3), 1.91 (s, 3H, 18-CH3), 2.27 (m, 2H, 14-CH2), 2.35 (s, 3H, OAc), 2.08
and 2.63 (2m, 2H, 6-CH2), 3.88 (d, 1H, J = 7.2 Hz, 3-CH), 4.22 and 4.33 (2d, 2H, J = 8.6 Hz, 20-CH2),
4.60 (t, 1H, J = 3.6 Hz, 2′-CH), 4.62 and 4.93 (2d, 2H, J = 11.6 Hz, Troc), 4.80 (s, 2H, Troc), 4.96 (d,
1H, J = 9.6 Hz, 5-CH), 4.97 (d, 1H, J = 9.2 Hz, 3′-CH), 5.53 (dd, 1H, J = 10.8, 7.2 Hz, 7-CH), 5.69 (d,
1H, J = 7.2 Hz, 2-CH), 5.92 (d, 1H, J = 9.2 Hz, -CONH-), 6.20 (t, 1H, J = 8.8 Hz, 13-CH), 6.23 (s, 1H,
10-CH), 7.11 (m, 2H, 3′-Ph), 7.24 (m, 3H, 3′-Ph), 7.40 (m, 2H, -PhBr), 7.46 (m, 2H, -PhBr), 7.50 (t,
2H, J = 7.8 Hz, m-OBz), 7.64 (t, 1H, J = 7.6 Hz, p-OBz), 8.09 (d, 2H, J = 7.6 Hz, o-OBz). 13C-NMR
(CDCl3) δ 200.57, 171.21, 171.02, 170.67, 166.77, 153.22, 141.85, 139.33, 136.12, 133.91, 132.43,
131.98, 130.12, 129.01, 128.72, 128.43, 127.55, 127.15, 126.96, 94.16, 83.57, 81.03, 79.10, 78.57,
74.57, 74.08, 72.11, 60.42, 59.57, 58.48, 56.30, 53.43, 46.95, 43.03, 35.52, 33.29, 26.51, 22.46, 21.05,

Molecules 2013, 18
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20.64, 18.42, 14.95, 14.20, 10.72. Anal. calcd. for C50H50BrCl6NO18S: C, 47.00; H, 3.94; N, 1.10.
Found: C, 47.30; H, 4.03; N, 1.17.
N-De-tert-butoxycarbonyl-N-(2,4,6-trimethyl)-phenylsulfonyl 7,10-di(2,2,2-trichloroethyloxy carbonyl)-
docetaxel (5j). Yield 68% (183 mg); mp 151–153 °C; 1H-NMR (CDCl3): δ 1.21 (s, 3H, 17-CH3), 1.26
(s, 3H, 16-CH3), 1.87 (s, 3H, 19-CH3), 1.92 (s, 3H, 18-CH3), 2.29 (m, 2H, 14-CH2), 2.23 (s, 3H,
p-3″-CH3), 2.32 (s, 3H, OAc), 2.08 and 2.63 (2m, 2H, 6-CH2), 2.50 (s, 6H, o-3″-CH3), 3.88 (d, 1H,
J = 6.8 Hz, 3-CH), 4.21 and 4.33 (2d, 2H, J = 8.6 Hz, 20-CH2), 4.54 (d, 1H, J = 3.6 Hz, 2′-CH), 4.62
and 4.93 (2d, 2H, J = 11.6 Hz, Troc), 4.75 (m, 1H, 3′-CH), 4.80 (s, 2H, Troc), 4.96 (d, 1H, J = 9.6 Hz,
5-CH), 5.53 (dd, 1H, J = 10.4, 7.2 Hz, 7-CH), 5.66 (d, 1H, J = 8.8 Hz, -CONH-), 5.70 (d, 1H, J = 6.8 Hz,
2-CH), 6.12 (t, 1H, J = 8.8 Hz, 13-CH), 6.23 (s, 1H, 10-CH), 6.78 (s, 2H, 3″-Ph), 7.10-7.22 (m, 5H,
3′-Ph), 7.53 (t, 2H, J = 7.8 Hz, m-OBz), 7.67 (t, 1H, J = 7.2 Hz, p-OBz), 8.10 (d, 2H, J = 7.2 Hz,
o-OBz). 13C-NMR (CDCl3) δ 200.63, 171.51, 170.31, 166.77, 153.22, 153.18, 142.38, 142.09, 138.60,
136.74, 134.20, 133.90, 132.26, 131.83, 130.08, 129.05, 128.71, 128.54, 128.35, 126.94, 94.17, 83.61,
80.90, 79.11, 78.59, 74.34, 74.10, 72.24, 59.39, 58.48, 56.24, 46.86, 43.05, 35.26, 33.27, 31.92, 29.68,
26.43, 22.87, 22.48, 20.85, 18.42, 14.73, 10.71. Anal. calcd. for C53H57Cl6NO18S: C, 51.30; H, 4.63; N,
1.13. Found: C, 51.53; H, 4.65; N, 1.17.
3.2.6. General Procedure for the Synthesis of 3a–j
To a solution of 5a–j (0.19 mmol) in methanol (10 mL) were added glacial acetic acid (4.60 mL)
and zinc powder (0.46 g, 7.08 mmol). After stirred at 50 °C for 1 h, the reaction mixture was filtered to
remove the zinc and solid formed. The filtrate was evaporated by distillation to give a white solid. The
obtained solid was then dissolved in ethyl acetate (60 mL), which was washed with saturated NaHCO3,
brine, dried over Na2SO4, and concentrated in vacuo. The obtained residue was further purified by
silica gel flash chromatography column (petroleum ether/acetone: 2/1) to give 3a–j.
N-De-tert-butoxycarbonyl-N-phenylsulfonyl docetaxel (3a). White powder; Yield 75% (121 mg); mp
1
174–175 °C; H-NMR (CDCl3): δ 1.09 (s, 3H, 17-CH3), 1.19 (s, 3H, 16-CH3), 1.73 (s, 3H, 19-CH3),
1.81 (s, 3H, 18-CH3), 2.15 (m, 2H, 14-CH2), 2.30 (s, 3H, OAc), 1.82 and 2.51 (2m, 2H,
6-CH2), 3.84 (d, 1H, J = 7.2 Hz, 3-CH), 4.20 and 4.26 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.23 (m, 1H,
7-CH), 4.50 (d, 1H, J = 4.0 Hz, 2′-CH), 4.89 (d, 1H, J = 9.6 Hz, 5-CH), 4.89 (m, 1H, 3′-CH), 5.22 (s,
1H, 10-CH), 5.63 (d, 1H, J = 7.2 Hz, 2-CH), 6.14 (t, 1H, J = 8.8 Hz, 13-CH), 6.35 (d, 1H, J = 6.0 Hz,
-CONH-), 7.09 (m, 2H, 3′-Ph), 7.14 (m, 3H, 3′-Ph), 7.24 (t, 2H, J = 8.0 Hz, m-PhSO2), 7.40 (t, 1H,
J = 7.6 Hz, p-PhSO2), 7.46 (t, 2H, J = 7.6 Hz, m-OBz), 7.58 (t, 1H, J = 7.6 Hz, p-OBz), 7.59 (d, 2H,
13
J = 7.6 Hz, o-PhSO2), 8.07 (d, 2H, J = 7.6 Hz, o-OBz); C-NMR (CD3COCD3) δ 210.54, 171.85,
170.02, 165.73, 141.70, 137.67, 137.40, 136.71, 133.15, 131.98, 130.50, 130.00, 128.56, 128.48,
128.03, 127.57, 127.54, 126.77, 84.16, 80.86, 77.87, 77.76, 75.97, 75.23, 74.92, 74.28, 71.52, 71.26,
60.51, 57.63, 54.08, 46.52, 46.52, 43.25, 36.68, 36.10, 26.27, 22.17, 20.62, 13.55, 9.52; HRMS (ESI)
m/z calcd. for C44H49NO14SNa+ [M+Na+]: 870.2771, found 870.2802.
N-De-tert-butoxycarbonyl-N-phenylmethylsulfonyl docetaxel (3b). White powder; Yield 74% (121
1
mg); mp 168–170 °C; H-NMR (CDCOCD3): δ 1.14 (s, 3H, 17-CH3), 1.21 (s, 3H, 16-CH3), 1.74 (s,

Molecules 2013, 18
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3H, 19-CH3), 1.89 (s, 3H, 18-CH3), 2.17 (m, 2H, 14-CH2), 2.41 (s, 3H, OAc), 1.85 and 2.46 (2m, 2H,
6-CH2), 3.89 (s, 1H, 2′-OH), 3.92 (d, 1H, J = 7.2 Hz, 3-CH), 4.09 and 4.22 (2d, 2H, J = 14.0 Hz,
CH2Ph), 4.16 and 4.19 (2d, 2H, J = 8.4 Hz, 20-CH2), 4.32 (m, 1H, 7-CH), 4.36 (br s, 1H, 10-OH), 4.64
(t, 1H, J = 5.2 Hz, 2′-CH), 4.97 (d, 1H, J = 9.2 Hz, 5-CH), 5.00 (d, 1H, J = 5.6 Hz, 3′-CH), 5.12 (m,
1H, -CONH-), 5.24 (d, 1H, J = 2.0 Hz,10-CH), 5.67 (d, 1H, J = 7.6 Hz, 2-CH), 6.22 (t, 1H, J = 8.8 Hz,
13-CH), 7.25-7.36 (m, 6H, 3′-Ph and 3″-Ph), 7.47 (t, 2H, J = 7.2 Hz, m-OBz), 7.55 (m, 4H, 3″-Ph),
13
7.66 (t, 1H, J = 7.2 Hz, p-OBz), 8.10 (d, 2H, J = 7.2 Hz, o-OBz); C-NMR (CD3COCD3) δ 210.54,
172.23, 170.07, 165.76, 138.92, 137.38, 136.73, 133.15, 130.94, 130.45, 130.05, 129.98, 128.55,
128.51, 128.19, 128.14, 128.00, 127.93, 84.18, 80.83, 77.83, 75.98, 75.20, 75.00, 74.28, 71.52, 71.16,
60.70, 59.68, 57.63, 54.09, 46.48, 43.24, 36.67, 35.98, 26.22, 22.29, 20.61, 18.00, 13.52, 9.52; HRMS
(ESI) m/z calcd. for C45H51NO14SNa+ [M+Na+]: 884.2928, found 884.2944.
N-De-tert-butoxycarbonyl-N-(4-methyl)-phenylsulfonyl docetaxel (3c). White powder; Yield 80% (131
1
mg); mp 172–174 °C; H-NMR (CDCl3): δ 1.10 (s, 3H, 17-CH3), 1.19 (s, 3H, 16-CH3), 1.73 (s, 3H,
19-CH3), 1.78 (s, 3H, 18-CH3), 2.14 (m, 2H, 14-CH2), 2.30 (s, 3H, OAc), 2.30 (s, 3H, CH3 in
4-methylphenyl), 1.83 and 2.52 (2m, 2H, 6-CH2), 3.84 (d, 1H, J = 6.8 Hz, 3-CH), 4.20 and 4.27 (2d,
2H, J = 8.4 Hz, 20-CH2), 4.21 (m, 1H, 7-CH), 4.50 (d, 1H, J = 3.6 Hz, 2′-CH), 4.89 (d, 1H, J = 9.2 Hz,
5-CH), 4.89 (m, 1H, 3′-CH), 5.20 (s, 1H, 10-CH), 5.63 (d, 1H, J = 7.6 Hz, 2-CH), 6.12 (m, 1H,
-CONH-), 6.13 (t, 1H, J = 9.2 Hz, 13-CH), 7.04 (d, 2H, J = 8.0 Hz, m-PhSO2), 7.11 (m, 2H, 3′-Ph),
7.16 (m, 3H, 3′-Ph), 7.47 (t, 2H, J = 8.0 Hz, m-OBz), 7.49 (d, 2H, J = 8.4 Hz, o-PhSO2), 7.59 (t, 1H,
J = 7.6 Hz, p-OBz), 8.07 (d, 2H, J = 7.6 Hz, o-OBz); 13C-NMR (CD3COCD3) δ 210.55, 171.86,
170.05, 165.75, 142.66, 138.85, 137.93, 137.44, 136.66, 133.17, 130.48, 130.00, 129.08, 128.92,
128.50, 128.20, 128.03, 127.79, 127.59, 127.43, 126.92, 126.84, 84.17, 80.86, 77.88, 77.77, 75.98,
75.23, 74.92, 74.29, 71.53, 71.26, 60.44, 57.64, 46.52, 43.24, 36.67, 36.09, 26.25, 22.16, 20.61, 20.47,
17.99, 13.55, 9.53; HRMS (ESI) m/z calcd. for C45H51NO14SNa+ [M+Na+]: 884.2928, found 884.2942.
N-De-tert-butoxycarbonyl-N-(4-methoxyl)-phenylsulfonyl docetaxel (3d). White powder; Yield 73%
1
(122 mg); mp 172–174 °C; H-NMR (CDCOCD3): δ 1.16 (s, 3H, 17-CH3), 1.23 (s, 3H,
16-CH3), 1.74 (s, 3H, 19-CH3), 1.89 (s, 3H, 18-CH3), 2.25 (m, 2H, 14-CH2), 2.40 (s, 3H, OAc), 1.86
and 2.45 (2m, 2H, 6-CH2), 3.82 (s, 3H, OCH3), 3.93 (d, 1H, J = 6.8 Hz, 3-CH), 3.93 (s, 1H, 2′-OH),
4.16 and 4.22 (2d, 2H, J = 8.2 Hz, 20-CH2), 4.31 (m, 1H, 7-CH), 4.37 (br s, 1H, 10-OH), 4.56 (d, 1H,
J = 4.0 Hz, 2′-CH), 4.91 (m, 1H, 3′-CH), 4.87 (m, 1H, -CONH-), 4.97 (d, 1H, J = 9.2 Hz, 5-CH), 5.24
(s, 1H, 10-CH), 5.69 (d, 1H, J = 6.8 Hz, 2-CH), 6.17 (t, 1H, J = 9.0 Hz, 13-CH), 6.85 (d, 2H,
J = 8.8 Hz, o-PhOCH3), 7.16 (t, 1H, J = 7.2 Hz, 3′-Ph), 7.22 (t, 2H, J = 7.2 Hz, 3′-Ph), 7.28 (d, 1H,
J = 7.2 Hz, 3′-Ph), 7.57 (t, 2H, J = 7.2 Hz, m-OBz), 7.60 (d, 2H, J = 8.8 Hz, m-PhOCH3), 7.67 (t, 1H,
J = 7.2 Hz, p-OBz), 8.13 (d, 2H, J = 7.6 Hz, o-OBz); 13C-NMR (CD3COCD3) δ 210.55, 171.88,
170.04, 165.75, 162.51, 137.88, 137.42, 136.69, 133.36, 133.16, 130.49, 130.01, 128.92, 128.50,
128.04, 127.61, 127.47, 113.69, 84.17, 80.85, 77.88, 75.97, 75.23, 74.95, 74.28, 71.53, 71.26, 60.44,
57.63, 55.12, 46.52, 43.24, 36.68, 36.11, 26.24, 22.17, 20.62, 13.57, 9.52; HRMS (ESI) m/z calcd. for
C45H51NO15SNa+ [M+Na+]: 900.2877, found 900.2889.

Molecules 2013, 18
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N-De-tert-butoxycarbonyl-N-(4-isopropyl)-phenylsulfonyl docetaxel (3e). White powder; Yield 77%
(130 mg); mp 171–173 °C; 1H-NMR (CDCOCD3): δ 1.17 (s, 3H, 17-CH3), 1.20 (s, 3H, 16-CH3), 1.22
(s, 3H, CH3 in i-Pr), 1.25 (s, 3H, CH3 in i-Pr), 1.75 (s, 3H, 19-CH3), 1.91 (s, 3H, 18-CH3), 2.29 (m, 2H,
14-CH2), 2.43 (s, 3H, OAc), 1.86 and 2.47 (2m, 2H, 6-CH2), 2.90 (m, 1H, CH in i-Pr), 3.95 (d, 1H,
J = 7.2 Hz, 3-CH), 3.96 (s, 1H, 2′-OH), 4.17 and 4.24 (2d, 2H, J = 8.2 Hz, 20-CH2), 4.32 (m, 1H,
7-CH), 4.38 (br s, 1H, 10-OH), 4.57 (d, 1H, J = 4.8 Hz, 2′-CH), 4.93 (d, 1H, J = 4.4 Hz, 3′-CH), 4.98
(d, 1H, J = 9.2 Hz, 5-CH), 5.25 (s, 1H, 10-CH), 5.69 (d, 1H, J = 7.6 Hz, 2-CH), 6.25 (t, 1H, J = 9.0 Hz,
13-CH), 7.17 (m, 8H, 3′-Ph and i-PrPh), 7.55 (d, 2H, J = 8.0 Hz, i-PrPh), 7.56 (t, 2H, J = 7.6 Hz,
13
m-OBz), 7.66 (t, 1H, J = 7.2 Hz, p-OBz), 8.14 (d, 2H, J = 7.2 Hz, o-OBz); C-NMR (CD3COCD3) δ
210.56, 171.93, 170.08, 165.79, 153.27, 138.97, 137.49, 137.40, 136.69, 133.15, 130.50, 130.03,
128.49, 128.21, 127.96, 127.76, 127.64, 127.45, 127.06, 127.00, 126.51, 126.39, 84.19, 80.87, 77.91,
77.80, 75.99, 75.27, 74.91, 74.29, 71.52, 71.30, 60.48, 57.64, 46.51, 43.27, 36.67, 36.13, 33.84, 26.30,
23.13, 23.05, 22.21, 20.68, 17.99, 15.37, 13.58, 9.56; HRMS (ESI) m/z calcd. for C47H55NO14SNa+
[M+Na+]: 912.3241, found 912.3239.
N-De-tert-butoxycarbonyl-N-(4-fluoro)-phenylsulfonyl docetaxel (3f). White powder; Yield 53%
1
(87 mg); mp 173–175 °C; H-NMR (CDCOCD3): δ 1.16 (s, 3H, 17-CH3), 1.23 (s, 3H, 16-CH3), 1.74
(s, 3H, 19-CH3), 1.90 (s, 3H, 18-CH3), 2.24 (m, 2H, 14-CH2), 2.41 (s, 3H, OAc), 1.85 and 2.46 (2m, 2H,
6-CH2), 3.93 (d, 1H, J = 7.2 Hz, 3-CH), 3.93 (s, 1H, 2′-OH), 4.16 and 4.22 (2d, 2H, J = 8.0 Hz, 20-CH2),
4.31 (m, 1H, 7-CH), 4.37 (br s, 1H, 10-OH), 4.57 (d, 1H, J = 4.8 Hz, 2′-CH), 4.95 (d, 1H, J = 4.8 Hz,
3′-CH), 4.97 (d, 1H, J = 9.0 Hz, 5-CH), 5.24 (s, 1H, 10-CH), 5.69 (d, 1H, J = 7.6 Hz, 2-CH), 6.19 (t, 1H,
J = 8.8 Hz, 13-CH), 7.09 (t, 2H, J = 7.2 Hz, 3′-Ph), 7.18 (d, 1H, J = 7.2 Hz, 3′-Ph), 7.21 (d, 2H, J = 6.8 Hz,
-PhF), 7.27 (d, 2H, J = 6.8 Hz, 3′-Ph), 7.57 (t, 2H, J = 8.0 Hz, m-OBz), 7.67 (t, 1H, J = 7.6 Hz,
p-OBz), 7.71 (dd, 2H, J = 8.8, 5.2 Hz, -PhF), 8.12 (d, 2H, J = 8.0 Hz, o-OBz); 13C-NMR (CD3COCD3)
δ 210.53, 171.84, 170.05, 165.74, 165.71, 163.21, 138.03, 138.00, 137.45, 137.37, 136.74, 133.17,
130.48, 130.00, 129.79, 129.70, 128.49, 128.07, 127.68, 127.60, 115.59, 115.36, 84.17, 80.86, 77.87,
75.97, 75.23, 74.90, 74.27, 71.52, 71.23, 60.64, 57.63, 46.51, 43.25, 36.67, 36.12, 26.23, 22.18, 20.63,
13.56, 9.53; HRMS (ESI) m/z calcd. for C44H48FNO14SNa+ [M+Na+]: 888.2677, found 888.2700.
N-De-tert-butoxycarbonyl-N-(4-trifluoromethyl)-phenylsulfonyl docetaxel (3g). White powder; Yield
1
57% (99 mg); mp 168–170 °C; H-NMR (CDCOCD3): δ 1.16 (s, 3H, 17-CH3), 1.23 (s, 3H, 16-CH3),
1.74 (s, 3H, 19-CH3), 1.91 (s, 3H, 18-CH3), 2.24 (m, 2H, 14-CH2), 2.42 (s, 3H, OAc), 1.86 and 2.47
(2m, 2H, 6-CH2), 3.93 (s, 1H, 2′-OH), 3.93 (d, 1H, J = 6.0 Hz, 3-CH), 4.16 and 4.23 (2d, 2H, J = 8.0 Hz,
20-CH2), 4.32 (m, 1H, 7-CH), 4.37 (br s, 1H, 10-OH), 4.59 (d, 1H, J = 4.8 Hz, 2′-CH), 4.97 (d, 1H,
J = 8.8 Hz, 5-CH), 4.98 (d, 1H, J = 4.4 Hz, 3′-CH), 5.24 (s, 1H, 10-CH), 5.69 (d, 1H, J = 6.8 Hz,
2-CH), 6.23 (t, 1H, J = 9.0 Hz, 13-CH), 7.16 (m, 3H, 3′-Ph), 7.24 (d, 1H, J = 6.8 Hz, 3′-Ph), 7.56 (t,
2H, J = 7.6 Hz, m-OBz), 7.66 (t, 1H, J = 7.6 Hz, p-OBz), 7.66 (d, 2H, J = 8.0 Hz, -PhCF3), 7.84 (d,
13
2H, J = 8.0 Hz, -PhCF3), 8.12 (d, 2H, J = 8.0 Hz, o-OBz); C-NMR (CD3COCD3) δ 210.51, 171.79,
170.06, 165.75, 145.38, 137.35, 137.03, 136.77, 133.16, 132.87, 132.55, 130.48, 130.00, 128.48,
128.06, 127.75, 127.66, 125.67, 125.63, 125.00, 122.30, 84.17, 80.87, 77.87, 75.97, 75.24, 74.82,
74.27, 71.52, 71.23, 60.81, 57.63, 46.51, 43.25, 36.66, 36.13, 26.24, 22.20, 20.65, 13.55, 9.53; HRMS
(ESI) m/z calcd. for C45H48F3NO14SNa+ [M+Na+]: 938.2645, found 938.2651.

Molecules 2013, 18
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N-De-tert-butoxycarbonyl-N-(4-chloro)-phenylsulfonyl docetaxel (3h). White powder; Yield 65% (109
1
mg); mp 178–180 °C; H-NMR (CDCOCD3): δ 1.16 (s, 3H, 17-CH3), 1.23 (s, 3H, 16-CH3), 1.74 (s,
3H, 19-CH3), 1.90 (s, 3H, 18-CH3), 2.24 (m, 2H, 14-CH2), 2.41 (s, 3H, OAc), 1.86 and 2.47 (2m, 2H,
6-CH2), 3.93 (d, 1H, J = 6.0 Hz, 3-CH), 3.93 (s, 1H, 2′-OH), 4.16 and 4.22 (2d, 2H, J = 8.0 Hz,
20-CH2), 4.32 (m, 1H, 7-CH), 4.38 (br s, 1H, 10-OH), 4.58 (d, 1H, J = 4.8 Hz, 2′-CH), 4.95 (d, 1H,
J = 4.8 Hz, 3′-CH), 4.97 (d, 1H, J = 10.2 Hz, 5-CH), 5.25 (s, 1H, 10-CH), 5.69 (d, 1H, J = 7.2 Hz,
2-CH), 6.20 (t, 1H, J = 9.0 Hz, 13-CH), 7.21 (m, 3H, 3′-Ph), 7.28 (d, 1H, J = 6.8 Hz, 3′-Ph), 7.36 (d,
2H, J = 8.4 Hz, -PhCl), 7.57 (t, 2H, J = 7.6 Hz, m-OBz), 7.65 (d, 2H, J = 8.8 Hz, -PhCl), 7.67 (t, 1H,
J = 7.2 Hz, p-OBz), 8.12 (d, 2H, J = 7.2 Hz, o-OBz); 13C-NMR (CD3COCD3) δ 210.53, 171.83,
170.07, 165.76, 140.49, 137.60, 137.44, 137.39, 136.74, 133.19, 130.47, 130.00, 128.67, 128.62,
128.50, 128.09, 127.70, 127.60, 84.18, 80.86, 77.88, 75.98, 75.24, 74.86, 74.28, 71.53, 71.25, 60.67,
57.64, 46.51, 43.26, 36.66, 36.12, 26.27, 22.20, 20.65, 13.57, 9.55; HRMS (ESI) m/z calcd. for
C44H48ClNO14SNa+ [M+Na+]: 904.2382, found 904.2359.
N-De-tert-butoxycarbonyl-N-(4-bromo)-phenylsulfonyl docetaxel (3i). White powder; Yield 61%
1
(107 mg); mp 179–181 °C; H-NMR (CDCOCD3): δ 1.16 (s, 3H, 17-CH3), 1.24 (s, 3H,
16-CH3), 1.74 (s, 3H, 19-CH3), 1.90 (s, 3H, 18-CH3), 2.24 (m, 2H, 14-CH2), 2.41 (s, 3H, OAc), 1.86
and 2.46 (2m, 2H, 6-CH2), 3.93 (s, 1H, 2′-OH), 3.93 (d, 1H, J = 6.0 Hz, 3-CH), 4.16 and 4.22 (2d, 2H,
J = 8.0 Hz, 20-CH2), 4.32 (m, 1H, 7-CH), 4.37 (br s, 1H, 10-OH), 4.58 (t, 1H, J = 5.0 Hz, 2′-CH), 4.95
(d, 1H, J = 5.2 Hz, 3′-CH), 4.95 (m, 1H, -CONH-), 4.97 (d, 1H, J = 7.6 Hz, 5-CH), 5.24 (d, 1H,
J = 2.0 Hz,10-CH), 5.69 (d, 1H, J = 7.2 Hz, 2-CH), 6.20 (t, 1H, J = 9.0 Hz, 13-CH), 7.22 (m, 3H, 3′-Ph),
7.28 (d, 1H, J = 6.8 Hz, 3′-Ph), 7.53 (t, 2H, J = 7.6 Hz, m-OBz), 7.58 (d, 4H, J = 8.4 Hz, -PhBr), 7.67
(t, 1H, J = 7.2 Hz, p-OBz), 8.12 (d, 2H, J = 7.2 Hz, o-OBz); 13C-NMR (CD3COCD3) δ 210.52, 171.81,
170.04, 165.74, 140.96, 137.43, 137.34, 136.76, 133.17, 131.68, 130.48, 130.00, 128.71, 128.49,
128.10, 127.71, 127.58, 126.11, 84.16, 80.86, 77.87, 75.97, 75.23, 74.86, 74.27, 71.52, 71.24, 60.67,
57.64, 46.51, 43.26, 36.68, 36.13, 26.28, 22.19, 20.63, 13.55, 9.53; HRMS (ESI) m/z calcd. for
C44H48BrNO14SNa+ [M+Na+]: 948.1877, found 948.1870.
N-De-tert-butoxycarbonyl-N-(2,4,6-trimethyl)-phenylsulfonyl docetaxel (3j). White powder; Yield
65% (110 mg); mp 165–167 °C; 1H-NMR (CDCOCD3): δ 1.13 (s, 3H, 17-CH3), 1.21 (s, 3H, 16-CH3),
1.73 (s, 3H, 19-CH3), 1.87 (s, 3H, 18-CH3), 2.16 (m, 2H, 14-CH2), 2.20 (s, 3H, p-3″-CH3), 2.36 (s, 3H,
OAc), 1.84 and 2.45 (2m, 2H, 6-CH2), 2.55 (s, 6H, o-3″-CH3), 3.83 (s, 1H, 2′-OH), 3.90 (d, 1H,
J = 7.2 Hz, 3-CH), 4.16 and 4.19 (2d, 2H, J = 8.0 Hz, 20-CH2), 4.30 (m, 1H, 7-CH), 4.35 (br s, 1H,
10-OH), 4.53 (t, 1H, J = 4.0 Hz, 2′-CH), 4.75 (d, 2H, J = 4.8 Hz, -CONH-), 4.96 (d, 1H,
J = 9.6 Hz, 5-CH), 5.00 (m, 1H, 3′-CH), 5.23 (d, 1H, J = 2.0 Hz,10-CH), 5.68 (d, 1H, J = 7.2 Hz,
2-CH), 6.09 (t, 1H, J = 8.4 Hz, 13-CH), 6.85 (s, 2H, 3″-Ph), 7.17-7.28 (m, 5H, 3′-Ph), 7.61 (t, 2H,
J = 8.0 Hz, m-OBz), 7.71 (t, 1H, J = 7.4 Hz, p-OBz), 8.11 (d, 2H, J = 7.6 Hz, o-OBz); 13C-NMR
(CD3COCD3) δ 210.52, 171.94, 169.86, 165.72, 141.79, 138.47, 137.86, 137.33, 136.77, 135.17,
133.22, 131.57, 130.46, 129.91, 128.52, 127.97, 127.61, 127.36, 84.13, 80.86, 77.77, 77.67, 75.93,
75.13, 74.77, 74.29, 71.52, 71.32, 60.19, 57.63, 46.50, 43.24, 36.67, 35.82, 26.21, 22.36, 22.21, 20.49,
19.91, 13.46, 9.47. HRMS (ESI) m/z calcd. for C47H55NO14SNa+ [M+Na+]: 912.3241, found 912.3264.

Molecules 2013, 18
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3.3. Biological Assays: Anti-HBV Tests
Drug stock solutions were prepared in DMSO and stored at −70 °C. Upon dilution into culture
medium, the final DMSO concentration was <1% DMSO (v/v), a concentration without effect on cell
replication. Cell culture and other procedures were the same as those reported previously [15]. A
HepG2-derived human hepatablastoma cell line, 2.2.15, was used in this study, which was transfected
with cloned HBV DNA to produce HBV particles. All stock cultures were grown in T-25 flasks
containing the DMEM supplemented with 10% (v/v) fetal bovine serum, 0.03% (v/v) L-glutamine,
100 μg/mL penicillin, 100 μg/mL streptomycin, and 380 μg/mL G418 at 37 °C in a humidified
atmosphere containing 5% CO2. After the HepG2 2.2.15 cell suspensions seeded in 24-well microtiter
plates were cultured for 48 h, they were incubated at 37 °C for 9 d in the presence of various
concentrations of drugs (200, 100, 50, 25, 12.5 and 6.25 μg/mL respectively) from DMSO-diluted
stock, and the medium was refreshed every 3 d. Then the culture supernatants were harvested to detect
the HBsAg and HBeAg secretion using diagnostic ELISA kits (Shanghai SIIC KEHUA Biotech Co., Ltd.,
Shanghai, China) as described in triplicate, and the standard error of the mean (SEM) of inhibition
values varied no more than 5%. Cell damage was assessed using the MTT assay.
4. Conclusions
In conclusion, we have provided a convenient route for the synthesis in high yields of
3′-N-phenylsulfonyl docetaxel analogs from the key intermediate N-phenylsulfonyl oxazolidine.
Among them, compounds 3e, 3g and 3j showed more potent inhibitory activity against HBeAg
secretion than the positive control lamivudine.
Supplementary Materials
Supplementary materials can be accessed at: http://www.mdpi.com/1420-3049/18/9/10189/s1.
Acknowledgments
Financial support by the National Natural Science Foundation of China (No: 81172920, 21242003),
the Shanghai Municipal Committee of Science and Technology (No: 10431903100), and the National
Basic Research Program of China (973 Program, No: 2010CB912603) are acknowledged. We would
like to thank Pei Zhou for the biological assays.
Conflicts of Interest
The authors declare no conflict of interest.
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Sample Availability: Samples of the compounds are available from the authors.
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