The first synthesis of optically active 1-substituted taurines

Article abstract of DOI:10.1002/hc.20133

Optically active 1-substituted taurines, a type of important sulfur analogues of naturally occurring amino acids, and their N-benzyloxycarbonyl- protected derivatives were synthesized from the corresponding optically active β-amino secondary alcohols in t

Full text of DOI:10.1002/hc.20133

Heteroatom Chemistry
Volume 16, Number 6, 2005
The First Synthesis of Optically Active
1-Substituted Taurines
Jiaxi Xu, Shu Xu, and Qihan Zhang
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education,
Department of Chemical Biology, College of Chemistry and Molecular Engineering,
Peking University, Beijing 100871, People’s Republic of China
Received 16 November 2003; revised 22 July 2004 and 25 February 2005
and their derivatives have been developed [5,6]. For
ABSTRACT: Optically active 1-substituted taurines,
aminoalkanesulfonic acids, β-aminoalkanesulfonic
a type of important sulfur analogues of naturally
acids are very important sulfur analogues of
occurring amino acids, and their N-benzyloxycar-
naturally occurring amino acids because α-amino-
bonyl-protected derivatives were synthesized from the
alkanesulfonic acids and their derivatives are un-
corresponding optically active β-amino secondary
stable. 1-Substituted 2-aminoethanesulfonic acids
alcohols in three steps via N-protection with ben-
(1-substituted taurines) and 2-substituted 2-amino-
zyl chloroformate, substitution with thiolacetic acid
ethanesulfonic acids (2-substituted taurines) are
under Mitsunobu conditions, and oxidation with
two types of structural analogues of naturally
ꢀ
C
performic acid.
2005 Wiley Periodicals, Inc. Het-
occurring amino acids for β-aminoalkanesulfonic
acids. Optically active 2-substituted taurines have
been synthesized effectively from optically active
β-amino primary alcohols [3,7–16], which were
easily obtained by reduction of natural amino acids,
via sulfite displacement of their methanesulfonates
[7–10], or peroxy acid oxidation of their thioacetates
[11–15], and sulfite ring opening of optically active
aziridines [16]. But little attention has been paid
to synthesis of 1-substituted taurines [13,17–19].
Braghiroli and his coworkers attempted to syn-
thesize optically active 1-substituted taurines from
optically active β-amino secondary alcohols and
failed to do so [20]. Liskamp’s group prepared sev-
eral 1-alkyltaurine-containing sulfonopeptides by
the alkylation of taurine-containing sulfonopeptides
[21,22] and by the acylation of 1-substituted 2-N-
protected aminoethanesulfinyl chloride to amino
acid esters and followed oxidation [18]. To our best
knowledge, there is no report on the preparation
of optically active 1-substituted taurines till now.
We herein report the preparation of optically active
1-substituted taurines from optically active β-amino
secondary alcohols.
eroatom Chem 16:466–471, 2005; Published online in
Wiley InterScience (www.interscience.wiley.com). DOI
10.1002/hc.20133
INTRODUCTION
During the last decade, aminoalkylphosphonic acid
and aminoalkanesulfonic acid derivatives have been
widely used as enzyme inhibitors and heptans in
the development of catalytic antibodies because
of their tetrahedrally structural properties [1–3].
On the other hand, several 2-aminoalkanesulfonic
acids have been found in many mammalian tissues
till now and are involved in various and important
physiological processes [4]. To date many methods
for the synthesis of aminoalkylphosphonic acids
Correspondence to: J. Xu; e-mail: jxxu@pku.edu.cn.
Contract grant sponsor: National Natural Science Foundation
of China, Ministry of Education of People’s Republic of China.
Contract grant number: 20272002.
Contract grant sponsor: Peking University (President grant).
2005 Wiley Periodicals, Inc.
c
ꢀ
466

The First Synthesis of Optically Active 1-Substituted Taurines 467
RESULTS AND DISCUSSION
N-benzyloxycarbonyl protected taurines 5 were
obtained. In current reaction conditions, products
4 and 5 should not lose optical purities compared
with compounds 3 because optically active amino
acids can be obtained via hydrolysis of peptides and
proteins in 6 mol/L HCl in a sealed tube at 110◦C
for 24 h. Substituted taurines are sulfur analogues
of naturally occurring amino acids. They should
show similar properties with amino acids. Thus,
they should be stable in acidic conditions. On the
other hand, both of enantiomers of substituted
taurines with almost same specific rotation values
and opposite sign were obtained. This supports
our assumption. The free 1-substituted taurines 4
can also be obtained by treatment of 1-substituted
N-benzyloxycarbonyl protected taurines 5 with
formic acid under refluxing conditions. In general,
the benzyloxycarbonyl group is removed with Pd/C
under hydrogen atmosphere [11]. However, the
current method can avoid hydrogenolytic cleavage
on the benzylic position for products 5a. It is
an alternative method for the deprotection of a
benzyloxycarbonyl group.
As part of a program to synthesize structural analogs
of naturally occurring amino acids, we sought to
prepare optically active 1-substituted taurines. Opti-
cally active β-amino secondary alcohols are impor-
tant key intermediates for synthesizing optically
active 1-substituted taurines (see Scheme 1). First,
optically active β-amino secondary alcohols 1 were
protected with benzyl chloroformate to give
1-(benzyloxycarbonyl)amino-2-alkanols [benzyl N-
(2-hydroxyalkyl) carbamates] 2, which were con-
verted to the corresponding thioacetates 3 in a
Mitsunobu displacement reaction using DEAD
(diethyl azodicarboxylate), triphenylphosphine, and
thiolacetic acid [11–13], in which a Walden inversion
occurs. HPLC analysis on a chiral column indicated
that the benzyl N-(2-hydroxyalkyl) carbamates 2
occurred in a complete configurational inversion to
yield the optically active corresponding thioacetates
3 in the Mitsunobu reaction except for some acetate
by-products. Although vicinal N-acylamino alcohols
yield oxazoline or oxazole derivatives as main by-
products or desired products under the Mitsunobu
conditions in most cases [23–26], no oxazoline
derivative was found in the reaction mixture due
to the hard enolization of the carbamates and the
existence of a strong nucleophilic thioacetate anion
in the reaction systems. The thioacetates 3 were
subsequently oxidized with performic acid, in situ
generated by mixing formic acid and hydrogen
peroxide, under refluxing conditions to afford
1-substituted taurines 4 directly in good yields after
removal of solvent and excess performic acid by
evaporation under reduced pressure, washing with
chloroform, and crystallization from ethanol. It has
been found that the reaction mixture was mixed
with silica gel, evaporated at room temperature,
and separated on a silica gel column, 1-substituted
CONCLUSION
In summary, optically active 2-substituted tau-
rines were prepared from optically active 2-
amino-1-alkanols previously, herein optically
active 1-substituted taurines were synthesized from
corresponding optically active β-amino secondary
alcohols by employing N-protected 1-amino-2-alkyl
thioacetates as key intermediates. As another type
of important sulfur analogues of naturally occurring
amino acids, optically active 1-substituted taurines
could be used as the structural analogues of natu-
rally occurring 2-substituted 2-aminoethanesulfonic
acids for studies of some physiological processes.
SCHEME 1 Synthesis of optically active 1-substituted taurines.

468 Xu, Xu, and Zhang
N-Protected optically active 1-substituted taurines
are also very important building blocks for synthe-
sis of α-substituted β-sulfonopeptides and other
1-substituted-2-aminoethanesulfonic acid contain-
ing compounds.
(S)-Benzyl N-(2-hydroxy-2-phenylethyl) Carba-
mate (S)-2a. Colorless crystal; yield: 86%; mp: 80–
81◦C. Rf = 0.40 (petroleum ether: AcOEt = 2:1, silica
gel plate). [α]25 = +28.7 (c, 1.10, CHCl3). Lit [28]: mp
97–99◦C; [α]D25D = +27.16 (c, 0.93, CHCl3), 64% ee.
EXPERIMENTAL
General Method
(R)-Benzyl N-(2-hydroxypropyl) Carbamate (R)-
2b. Colorless oil, yield 77%. Rf = 0.35 (petroleum
ether: AcOEt = 2:1, silica gel plate). [α]2D5 = –9.66 (c,
5.03, MeOH). Lit [29]: [α]2D5 = −9.47 (c, 4.68, MeOH).
Melting points were measured on a Yanaco MP-500
melting point apparatus and are uncorrected. 1H
NMR and 13C NMR spectra were recorded on a Var-
ian Mercury 200 (200 MHz) or Mercury Plus 300
(300 MHz) spectrometer in CDCl3 with TMS as an
internal standard or in DMSO-d6. Mass spectra were
obtained on a VG-ZAB-HS mass spectrometer or a
Bruker ESQUIRE∼LCTM ESI ion trap spectrometer.
CHN analyses were recorded on an Elementar Vario
EL analyzer. Optical rotations were measured on a
Perkin Elmer 341LC polarimeter with a thermally
jacketed 10 cm cell (concentration c given as g/100
mL). IR spectra were taken on a Brucker Vector 22
FT-IR spectrophotometer in KBr pellet. The analyti-
cal data of all known compounds are identical to
those earlier reported in the literature [27–29].
(R)- And (S)-amino alcohols were purchased
from Aldrich and Acros Chemical Co., Inc. THF was
heated under reflux over sodium and distilled prior
to use. Triethylamine was heated under reflux over
sodium hydroxide and distilled prior to use.
(S)-Benzyl N-(2-hydroxypropyl) Carbamate (S)-
2b. Colorless oil, yield 77%. Rf = 0.35 (petroleum
ether: AcOEt = 2:1, silica gel plate). [α]2D5 = +9.85
(c, 4.63, MeOH). +11.7 (c, 0.99, CHCl3). IR (KBr):
1
ν 3419, 3332 (NH, OH), 1707 (C O) cm−1; H NMR
(300 MHz, CDCl3) δ 7.407.22 (m, 5H, ArH), 5.22 (s,
br, 1H, NH), 5.10 (s, 2H, OCH2), 4.68 (s, br, 1H, OH),
3.90 (m, 1H, CH), 3.33 (m, 1H, H in CH2), 3.05 (m,
1H, H in CH2), 1.17 (d, J = 6.3 Hz, 3H, CH3); 13C
NMR (75.5 MHz, CDCl3) δ 157.01, 136.30, 128.33,
127.94, 127.86, 66.91, 66.65, 48.10, 20.33. MS (EI)
m/z: 209 (M+). Anal. Calcd for C11H15NO3 (209.24):
C, 63.14; H, 7.23; N, 6.69. Found: C, 63.41; H, 7.47;
N, 6.46%.
General Procedure for Synthesis of Optically
Active 1-Substituted 2-(Benzyloxycarbonyl)
aminoethyl Thioacetates (R)- and (S)-3
Diethyl azodicarboxylate (1.74 g, 10 mmol) in an-
hydrous tetrahydrofuran (6 mL) was added to an
efficiently stirred solution of triphenylphosphine
(2.62 g, 10 mmol) in 12 mL of anhydrous tetrahy-
drofuran at −10◦C. The mixture was stirred at −10◦C
for 0.5 h. A white precipitate appeared. The benzyl
N-(2-hydroxyalkyl) carbamate 2 (5 mmol) and thio-
lacetic acid (0.76 g, 10 mmol) in 12 mL of tetrahy-
drofuran were added dropwise over 30 min, and
the mixture was stirred for 1 h at −10◦C and at
room temperature for 20 h. The resulting mixture
was concentrated in reduced pressure. The triph-
enylphosphine oxide was crystallized upon addi-
tion of a mixture of ethyl acetate and petroleum
ether. The combined filtrates were concentrated in
vacuo and subject to silica gel column chromato-
graphic separation with a mixture of petroleum
ether and ethyl ether (8:1, v/v) as an eluent to give
thioacetate 3. Optical purity determination condi-
tions: Chiralcel OD column 4.6 × 250 mm, eluent:
hexane: 2-propanol (80:20, v/v) for the determina-
tion of 2-(benzyloxycarbonyl)amino-1-phenylethyl
thioacetates with (R)-3a (t = 17.75 min) and (S)-
3a (t = 22.34); hexane: 2-propanol (99:1, v/v) for
General Procedure for Synthesis of Optically
Active Benzyl N-(2-hydroxyalkyl) Carbamate
(R)- and (S)-2
To a solution of the amino alcohol 1 (50 mmol) in
CH2Cl2 (50 mL) was added 50 mL of 1 N NaOH.
The mixture was cooled in an ice bath and 50%
benzyl chloroformate in toluene (17.06 g, 50 mmol)
was added keeping the temperature at 0–5◦C. After
stirring overnight at room temperature, the organic
layer was separated, washed with water (2 × 20 mL),
dried over anhydrous MgSO4. The solvent was re-
moved under reduced pressure to give the N-Cbz
protected amino alcohol [benzyl N-(2-hydroxyalkyl)
carbamate] 2. Benzyl N-(2-hydroxy-2-phenylethyl)
carbamates 2a were obtained as colorless crystals
after crystallized from a mixture of petroleum ether
and ethyl acetate.
(R)-Benzyl N-(2-hydroxy-2-phenylethyl) Carba-
mate (R)-2a. Colorless crystal; yield: 76%; mp: 82–
83◦C. Rf = 0.40 (petroleum ether: AcOEt = 2:1, sil-
ica gel plate). [α]2D5 = −28.0 (c, 1.02, CHCl3). Lit [27]:
[α]2D0 = −25.0 (c, 2, CHCl3), ee 83%.

The First Synthesis of Optically Active 1-Substituted Taurines 469
the determination of 2-(benzyloxycarbonyl)amino-
1-methylethyl thioacetates with (R)-3b (t = 33.79
min), and (S)-3b (t = 36.89), flow rate: 0.6 mL/min.
(S)-2-(Benzyloxycarbonyl)amino-1-methylethyl
Thioacetate (S)-3b. Colorless oil, yield 67%, >99%
ee. Rf = 0.25 (petroleum ether: ether = 4:1, silica
gel plate). [α]2D5 = −29.5 (c, 1.13, CHCl3). IR (KBr): ν
3342 (NH), 1720 (C O), 1693 (C O) cm−1; 1H NMR
(300 MHz, CDCl3) δ 7.40–7.27 (m, 5H, Ph), 5.10 (s,
2H, OCH2), 5.02 (s, br, 1H, NH), 3.66 (ddq, J = 6.3,
6.9, 6.9 Hz, 1H, CH), 3.43 (ddd, J = 5.7, 6.3, 13.9
Hz, 1H in NCH2), 3.31 (ddd, J = 6.9, 6.9, 13.9 Hz,
1H in NCH2), 2.30 (s, 3H, COCH3), 1.30 (d, J = 6.9
Hz, 3H, CH3); 13C NMR (75.5 MHz, CDCl3) δ 195.69,
156.41, 136.35, 128.45, 128.07, 127.98, 66.73, 46.08,
39.72, 30.68, 18.06; MS (EI) m/z: 267 (M+, 1.1), 224
(M+-Ac, 1.2), 191 (M+-AcSH, 9.3), 108 (PhCH2OH+,
13.7), 107 (PhCH2O+, 8.2), 91 (PhCH2+, 100). Anal.
Calcd for C13H17NO3S (267.35): C, 58.40; H, 6.41; N,
5.24. Found: C, 58.51; H, 6.70; N, 5.09%.
(R)-2-(Benzyloxycarbonyl)amino-1-phenylethyl
Thioacetate (R)-3a. Colorless crystal; yield 67%,
mp 73–74◦C, >99% ee. Rf = 0.30 (petroleum ether:
ether = 3:1, silica gel plate). [α]2D5 = −126 (c, 1.12,
CHCl3). IR (KBr): ν 3343 (NH), 1720 (C O), 1695
(C O) cm−1; 1H NMR (300 MHz, CDCl3) δ 7.32–7.29
(m, 10H, ArH), 5.08 (s, 2H, OCH2), 4.96 (s, 1H,
NH), 4.72 (t, J = 7.5 Hz, 1H, CH), 3.68 (dd, J = 6.9,
7.5 Hz, 2H, NCH2), 2.30 (s, 3H, CH3); 13C NMR
(75.5 MHz, CDCl3) δ 194.33, 156.09, 138.46, 136.38,
128.77, 128.64, 128.38, 127.98, 127.84, 127.79, 66.69,
47.81, 45.55, 30.34; MS (EI) m/z: 329 (M+, 1.2), 286
(M+-Ac, 14.9), 253 (M+-AcSH, 1.1), 238 (M+-PhCH2,
19.8), 108 (PhCH2OH+, 5.9), 91 (PhCH+2 , 100). Anal.
Calcd for C18H19NO3S (329.41): C, 65.63; H, 5.81; N,
4.25. Found: C, 65.51; H, 5.71; N, 4.46%.
General Procedure for Synthesis of Optically
Active 1-Substituted Taurines (R)- and (S)-4
(S)-2-(Benzyloxycarbonyl)amino-1-phenylethyl
Thioacetate (S)-3a. Colorless crystal; yield 63%,
mp 72.5–73.5◦C, >99% ee. Rf = 0.30 (petroleum
ether: ether = 3:1, silica gel plate). [α]2D5 = +122 (c,
0.72, CHCl3). IR (KBr): ν 3342 (NH), 1718 (C O),
1696 (C O) cm−1; 1H NMR (300 MHz, CDCl3) ꢀ
7.32–7.29 (m, 10H, ArH), 5.08 (s, 2H, OCH2), 4.96
(s, 1H, NH), 4.72 (t, J = 7.5 Hz, 1H, CH), 3.68 (dd,
J = 6.9, 7.5 Hz, 2H, NCH2), 2.30 (s, 3H, CH3);13C
NMR (75.5 MHz, CDCl3) δ 194.27, 156.09, 138.46,
136.38, 128.77, 128.64, 128.38, 127.98, 127.84,
127.79, 66.69, 47.81, 45.55, 30.34; MS (EI) m/z: 329
(M+, 1.2), 286 (M+-Ac, 14.8), 253 (M+-AcSH, 1.2),
238 (M+-PhCH2, 19.8), 108 (PhCH2OH+, 5.9), 91
(PhCH+2 , 100). Anal. Calcd for C18H19NO3S (329.41):
C, 65.63; H, 5.81; N, 4.25. Found: C, 65.51; H, 5.69;
N, 4.05%.
To a performic acid solution, prepared by mixing
and stirring 30% H2O2 (1.2 mL) and 88% HCO2H
(12 mL) at room temperature for 1 h and cooled in
an ice bath were added thioacetate derivatives 3 (2
mmol) in 88% HCO2H (2.7 mL) dropwise, the result-
ing mixture was refluxed and stirred overnight. After
removal of solvent and washing with chloroform, the
residue was crystallized from methanol to give the
pure 1-substituted taurines 4.
(R)-2-Amino-1-phenylethanesulfonic Acid (R)-4a.
Colorless crystal; yield: 96%; mp >360◦C. [α]D25
=
−4.98 (c, 0.91, H2O). IR (KBr): ν 3424, 3217, 3061
+
1
(NH3 ), 1212 (SO2), 1170 (SO2) cm−1; H NMR (300
MHz, DMSO-d6) δ 7.78 (s, br, 3H, NH3), 7.29 (s, 5H,
ArH), 3.88 (dd, J = 4.5, 9.9 Hz, 1H, H in CH2), 3.45
(d, J = 4.5 Hz, 1H, H in CH2), 3.08 (d, J = 9.9 Hz,
1H, CH); 13C NMR (75.5 MHz, DMSO-d6) δ 136.11,
129.06, 127.93, 127.21, 61.56, 40.88. MS (ESI, posi-
tive ion) m/z: 202 (MH)+. Anal. Calcd for C8H11NO3S
(201.24): C, 47.75; H, 5.51; N, 6.96. Found: C, 47.60;
H, 5.77; N, 7.14%.
(R)-2-(Benzyloxycarbonyl)amino-1-methylethyl
Thioacetate (R)-3b. Colorless oil, yield 54%, >99%
ee. Rf = 0.25 (petroleum ether: ether = 4:1, silica
gel plate). [α]2D5 = +29.7 (c, 1.22, CHCl3). IR (KBr): ν
3344 (NH), 1721 (C O), 1692 (C O) cm−1; 1H NMR
(300 MHz, CDCl3) δ 7.40–7.27 (m, 5H, Ph), 5.10 (s,
2H, OCH2), 5.02 (s, br, 1H, NH), 3.66 (ddq, J = 6.3,
6.9, 6.9 Hz, 1H, CH), 3.43 (ddd, J = 5.7, 6.3, 13.9
Hz, 1H, H in NCH2), 3.31 (ddd, J = 6.9, 6.9, 13.9
Hz, 1H, H in NCH2), 2.30 (s, 3H, COCH3), 1.30 (d,
J = 6.9 Hz, 3H, CH3); 13C NMR (75.5 MHz, CDCl3)
δ 195.69, 156.41, 136.35, 128.45, 128.07, 127.98,
66.73, 46.08, 39.72, 30.68, 18.06; MS (EI) m/z: 267
(M+, 1.2), 224 (M+-Ac, 1.2), 191 (M+-AcSH, 9.2), 108
(PhCH2OH+, 13.7), 107 (PhCH2O+, 8.2), 91 (PhCH+2 ,
100). Anal. Calcd for C13H17NO3S (267.35): C, 58.40;
H, 6.41; N, 5.24. Found: C, 58.61; H, 6.29; N, 5.09%.
(S)-2-Amino-1-phenylethanesulfonic Acid (S)- 4a.
Colorless crystal; yield: 92%; mp >360◦C. [α]D25
=
+4.80 (c, 0.77, H2O). IR (KBr): ν 3421, 3215, 3058
+
1
(NH3 ), 1214 (SO2), 1170 (SO2) cm−1; H NMR (300
MHz, DMSO-d6) δ 7.82 (s, br, 3H, NH3), 7.29 (s, 5H,
ArH), 3.88 (dd, J = 4.5, 9.9 Hz, 1H, H in CH2), 3.46
(m, 1H, H in CH2), 3.09 (d, J = 9.9 Hz, 1H, CH); 13
C
NMR (75.5 MHz, DMSO-d6) δ 136.09, 129.07, 127.95,
127.30, 61.59, 40.91. MS (ESI, positive ion) m/z: 202
(MH)+. Anal. Calcd for C8H11NO3S (201.24): C, 47.75;
H, 5.51; N, 6.96. Found: C, 47.50; H, 5.79; N, 7.04%.

470 Xu, Xu, and Zhang
(R)-2-Amino-1-methylethanesulfonic Acid (R)-
4b. Colorless crystal; yield: 98%; mp: 236–238◦C.
[α]2D5 = −8.56 (c, 1.10, H2O). IR (KBr): ν 3140 (br,
(S)-2-(Benzyloxycarbonyl)amino-1-phenylethane-
sulfonic Acid (S)-5a. Colorless crystal; yield 93%,
mp 190–192◦C. Rf = 0.60 (CHCl3: MeOH = 4:1,
silica gel plate). [α]2D5 = −19.1 (c, 0.94, MeOH).
IR (KBr): ν 3413 (NH), 1698 (C O), 1222 (SO2),
1172 (SO2) cm−1; 1H NMR (200 MHz, d6-DMSO)
δ 7.36–7.22 (m, 10H, ArH), 6.99 (s, 1H, NH), 4.92
(s, 2H, OCH2), 3.78 (dd, J = 8.6, 14.6 Hz, 1H, CH),
3.64 (m, 2H, NCH2); 13C NMR (50 MHz, d6-DMSO)
δ 155.79, 137.48, 137.22, 129.48, 128.33, 127.66,
127.45, 127.40, 126.47, 65.05, 64.42, 42.55; MS
(ESI, negative ion) m/z: 334 (M-H)−. Anal. Calcd
for C16H17NO5S (335.38): C, 57.30; H, 5.11; N, 4.18.
Found: C, 57.52; H, 5.29; N, 4.06%.
1
NH), 1219 (SO2), 1171 (SO2) cm−1; H NMR (300
MHz, DMSO-d6) δ 3.87 (s, br, 3H, NH3), 2.88 (m, 2H,
CH2), 2.68 (m, 1H, CH), 1.10 (d, J = 6.6 Hz, 3H, CH3);
13C NMR (75.5 Hz, DMSO-d6) δ 51.12, 41.28, 13.94.
MS (ESI, positive ion) m/z: 140 (MH)+. Anal. Calcd
for C3H9NO3S (139.17): C, 25.89; H, 6.52; N, 10.06.
Found: C, 25.70; H, 6.78; N, 9.88%.
(S)-2-Amino-1-methylethanesulfonic Acid (S)-4b.
Colorless crystal; yield: 97%; mp 237–239◦C. [α]D25
=
+8.70 (c, 1.15, H2O). IR (KBr): ν 3138 (br, NH), 1213
(SO2), 1170 (SO2) cm−1; 1H NMR (300 MHz, DMSO-
d6) δ 3.93 (s, br, 3H, NH3), 2.89 (m, 2H, CH2), 2.67
(m, 1H, CH), 1.10 (d, J = 6.6 Hz, 3H, CH3); 13C NMR
(75.5 Hz, CDCl3) δ 51.59, 41.22, 13.75. MS (ESI, pos-
itive ion) m/z: 140 (MH)+. Anal. Calcd for C3H9NO3S
(139.17): C, 25.89; H, 6.52; N, 10.06. Found: C, 26.00;
H, 6.49; N, 9.89%.
(R)-2-(Benzyloxycarbonyl)amino-1-methyletha-
nesulfonic Acid (R)-5b. Colorless crystal; yield
94%, mp >360◦C. Rf = 0.60 (CHCl3: MeOH = 4:1,
silica gel plate). [α]2D5 = +3.96 (c, 1.11, DMSO).
IR (KBr): ν 3362 (NH), 1701 (C O), 1215 (SO2),
1170 (SO2) cm−1; 1H NMR (300 MHz, DMSO-d6)
δ 7.33 (s, 5H, Ph), 7.04 (s, 1H, NH), 4.99 (s, 2H,
OCH2), 3.40–3.28 (m, 1H, H in NCH2), 3.08 (ddd,
J = 7.5, 7.5, 12.9 Hz, 1H, H in NCH2), 2.57 (m, 1H,
CH), 1.06 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75.5
MHz, DMSO-d6) δ 156.11, 137.30, 128.47, 127.88,
127.80, 65.33, 53.66, 42.77, 13.80; MS (ESI, negative
ion) m/z: 272 (M-H)−. Anal. Calcd for C11H15NO5S
(273.31): C, 48.34; H, 5.53; N, 5.12. Found: C, 49.50;
H, 5.79; N, 5.00%.
General Procedure for Synthesis of Optically
Active 1-Substituted N- Benzyloxycarbonyl
Taurines (R)- and (S)-5
To a performic acid solution, prepared by mixing
and stirring 30% H2O2 (1.2 mL) and 88% HCO2H
(12 mL) at room temperature for 1 h and cooled in
an ice bath, was added thioacetate derivative 3 (2
mmol) in 88% HCO2H (2.7 mL) dropwise, keeping
the temperature at 0◦C. After the mixture was stirred
at 0◦C for an additional 2 h and at room temperature
for 20 h, the resulting mixture was mixed with silica
gel and evaporated to dry at room temperature. The
residue was separated on a silica gel column with
a mixture of chloroform and methanol in 20:1–10:1
(v/v), and methanol as eluents in order to give the
pure 1-substituted N-benzyloxycarbonyl taurines 5.
(S)-1-(Benzyloxycarbonyl)amino-2-propanesulfo-
nic Acid (S)-5b. Colorless crystal; yield 90%, mp
>360◦C. Rf = 0.60 (CHCl3: MeOH = 4:1, silica gel
plate). [α]2D5 = – 4.01 (c, 1.19, DMSO). IR (KBr): ν
3360 (NH), 1700 (C O), 1216 (SO2), 1172 (SO2)
cm−1; 1H NMR (300 MHz, DMSO-d6) δ 7.33 (m,
5H, Ph), 7.04 (s, 1H, NH), 4.99 (s, 2H, OCH2), 3.34
(ddd, J = 4.5, 4.5, 12.9 Hz, 1H in NCH2), 3.08 (ddd,
J = 7.5, 7.5, 12.9 Hz, 1H in NCH2), 2.57 (m, 1H,
CH), 1.06 (d, J = 6.9 Hz, 3H, CH3); 13C NMR (75.5
MHz, DMSO-d6) δ 156.11, 137.30, 128.47, 127.88,
127.80, 65.33, 53.66, 42.77, 13.80; MS (ESI, negative
ion) m/z: 272 (M-H)−. Anal. Calcd for C11H15NO5S
(273.31): C, 48.34; H, 5.53; N, 5.12. Found: C, 48.55;
H, 5.74; N, 4.96%.
(R)-2-(Benzyloxycarbonyl)amino-1-phenyletha-
nesulfonic Acid (R)-5a. Colorless crystal; yield
95%, mp 190–192◦C. Rf = 0.60 (CHCl3: MeOH =
4:1, silica gel plate). [α]2D5 = +19.4 (c, 1.14, MeOH).
IR (KBr): ν 3411 (NH), 1699 (C O), 1220 (SO2),
1171 (SO2) cm−1; 1H NMR (200 MHz, d6-DMSO)
δ 7.36–7.22 (m, 10H, ArH), 7.00 (s, 1H, NH), 4.92
(s, 2H, OCH2), 3.79 (dd, J = 8.6, 14.6 Hz, 1H, CH),
3.64 (m, 2H, NCH2); 13C NMR (50 MHz, d6-DMSO)
δ 155.79, 137.48, 137.22, 129.48, 128.33, 127.66,
127.45, 127.40, 126.47, 65.05, 64.42, 42.55; MS
(ESI, negative ion) m/z: 334 (M-H)−. Anal. Calcd
for C16H17NO5S (335.38): C, 57.30; H, 5.11; N, 4.18.
Found: C, 57.45; H, 5.19; N, 4.01%.
General Procedure for Synthesis of Optically
Active 1-Substituted Taurines (R)- and (S)-4
from Optically Active 1-Substituted N-Protected
Taurines (R)- and (S)-5
1-Substituted N-benzyloxycarbonyl taurine 5 (0.6
mmol) was dissolved in formic acid (5 mL). The re-
sulting solution was stirred and refluxed overnight.

The First Synthesis of Optically Active 1-Substituted Taurines 471
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After removal of solvent, water was added and
removed under reduced pressure three times for
azeotropical removal of benzyl alcohol. The residue
was refluxed in chloroform and cooled to room tem-
perature. Crystallized optically active 1-substituted
taurines 4 were obtained after filtration and wash-
ing with chloroform.
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