Synthesis of 4-mercapto-l-lysine derivatives: Potential building blocks for sequential native chemical ligation

Article abstract of DOI:10.1016/j.bmcl.2009.09.107

A general and diastereoselective synthesis of (2S, 4S)-4-mercapto-l-lysine derivative was described. The key features of this synthesis include Zn-mediated diastereoselective Reformatsky reaction and selective reduction of methyl ester with sodium borohyd

Full text of DOI:10.1016/j.bmcl.2009.09.107

Bioorganic & Medicinal Chemistry Letters 19 (2009) 6268–6271
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Synthesis of 4-mercapto-L-lysine derivatives: Potential building blocks for
sequential native chemical ligation
Kalyan Kumar Pasunooti a, , Renliang Yang b, , Seenuvasan Vedachalam a, Bala Kishan Gorityala a,
a,
Chuan-Fa Liu b, , Xue-Wei Liu
*
*
a Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore 637371, Singapore
b Chemical Biology and Biotechnology Division, School of Biological Sciences, Nanyang Technological University, Singapore 637551, Singapore
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 July 2009
Revised 5 September 2009
Accepted 26 September 2009
Available online 3 October 2009
A general and diastereoselective synthesis of (2S, 4S)-4-mercapto-L-lysine derivative was described. The
key features of this synthesis include Zn-mediated diastereoselective Reformatsky reaction and selective
reduction of methyl ester with sodium borohydride. Introduction of thiol functional group on lysine side
chain proved to be appropriate for dual native chemical ligation. This methodology allows to develop var-
ious 4-substituted L-lysine derivatives.
Ó 2009 Elsevier Ltd. All rights reserved.
Keywords:
Reformatsky reaction
Amino acids
Native chemical ligation
L-Lysine derivatives
Cysteine-mediated native chemical ligation become the most
Step 3
O
attractive methodology for the preparation of novel peptides and
protein domains.1 Since its development it has become a powerful
tool for the chemical synthesis of linear peptides.2 This technique
relies on the combination of a N-terminal cysteine residue with a
C-terminal thioester to form a peptide bond.3–5 Unfortunately, very
few natural thiol-containing amino acids are available for peptide
ligation to form new type peptides. For the past few years various
chemical ligation methodologies have been developed. Wong and
co-workers developed cysteine-free ligation by incorporating a
thiol-containing sugar auxiliary on N-terminal serine, which al-
lows direct access to glycopeptides.6 In this Letter, we described
peptide 3
R1S
NHCbz
MeS
S
Step 2
O
OH
Step 1
H2N
BocHN
O
peptide 2
SR1
peptide 1
Figure 1. 4-Mercapto-
L
-lysine mediated sequential native chemical ligation that
the synthesis of 4-mercapto-L-lysine which serves as a pivotal
provides branched peptides.
building block for the assembly of branched peptides by native
chemical ligation.
We chose 4-mercapto-
native chemical ligation for the following reasons. (1) thio group
lies between the -amino group and the side chain amino group
L-lysine derivative as a mediator for dual
tive molecule which enhances the biological activity relative to
the parent molecule.7 The hydroxyl analogue 3a and 3b are also
useful precursors in many biological active components (Fig. 2).8
a
of lysine, which allows double native chemical ligation and fur-
nishes branched peptides, as shown in Figure 1. Likely, this new
branched structure endows the peptides or proteins with new
Synthesis of these functionalized
ing task due to the multiple functionality of
we developed a new methodology to introduce a thio group onto
the 4-position of -lysine side chain by exploiting Reformatsky
L
-lysine derivatives is a challeng-
L-lysine. In this work,
property and capacity. (2)
a necessary building block of proteins in the body. The substituted
-lysine derivatives, such as (2S,4R)-4-fluoro- -lysine 2 is a bioac-
L-lysine is an essential amino acid and
L
reaction as a key step.
L
L
We envisioned that the chirally pure target molecule, (2S,4S)-4-
mercapto-
able -aspartic acid 4. The side chain homologation, stereoselective
introduction of thiol and amino groups are the key steps in our
strategy. As shown in Scheme 1, the conversion of -aspartic acid
L-lysine could be assembled from commercially avail-
L
* Corresponding authors. Tel.: +65 6316 8901; fax: +65 6791 1961 (X.-W.L.).
E-mail addresses: CFLiu@ntu.edu.sg (C.-F. Liu), xuewei@ntu.edu.sg (X.-W. Liu).
K. K. Pasunooti and R. L. Yang contributed equally to this paper.
L
0960-894X/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2009.09.107

K. K. Pasunooti et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6268–6271
6269
NH2 OH
NH2
F
Boc
Boc
NH OH
NH OR
(i)
HO
HO
HO
HO
NHCbz
NHCbz
NHCbz
NHCbz
CO2Me
CO2Me
tBuO2C
tBuO2C
O
O
O
2
1
7b
8a
8b
R = TBDPS
R = TBDMS
NH2 OH
NH2 OH
8c R = TPS
Scheme 3. Reagents and conditions: (i) general procedure for 8b, TBDPSCl,
imidazole, DCM, rt, 89%.
O
3a
3b
Figure 2. Some of 4-substituted L-lysine derivatives.
Table 1
Optimization of reaction conditions
4 to
a-tert-butyl-(S)-N-tert-butoxycarbonyl aspartate 5 in four
Boc
Boc
steps with good yields.9 Further, the protected aspartate 5 was
transformed in to the corresponding thioester through DCC cou-
pling at room temperature (yield 95%). The resulting thioester
was reduced with the aid of triethylsilane—10% Pd/C to provide
(S)-aspartate semi-aldehyde 6 in 85% yield.10
NH
NH
R1 R2
R1 R2
Reducing agent
EtOH, RT
CO2Me
tBuO2C
tBuO2C
OH
8
9
No.
R1
R2
Reducing agent
Solvent
Yield (%)
As shown in Scheme 2, the homologation of the side chain was
carried out via diastereoselective Reformatsky reaction between
(S)-aspartate semi-aldehyde 6 and methyl bromoacetate.11 The
resulting Reformatsky product has the same carbon skeleton as
in the target molecule, which allows easy access to a series of 4-
substituted lysine analogues by nucleophilic substitution of hydro-
xyl group. Optimization of reaction conditions identified, zinc and
trimethylsilylchloride in THF at 0 °C as the best condition to fur-
nish the desired product in quantitative yields.12 A reasonable dia-
stereoselectivity of erythro/threo (7a/7b, 3/7) was obtained and
the selectivity towards diastereomer 7b was quite favorable. It
was observed that these two diastereomers could be easily sepa-
rated by column chromatography.13
The enantiomerically pure Reformatsky products 7a and 7b
serve as useful precursors for native chemical ligation. The major
product (7b) of Reformatsky reaction was protected with various
protecting groups like, TBDMSCl (8a, 80%), TBDPSCl (8b, 89%),
and TPSCl (8c, 75%), as shown in Scheme 3. The selective reduction
of methyl ester to the corresponding terminal alcohol was initially
attempted by using different reducing agents like LiAlH4, DIBAL-H,
NaBH3CN, and NaBH4 (Table 1, entries 3–6). Among them, NaBH4
in ethanol at room temperature was found to be superior to other
reducing reagents in terms of yields (Table 1, entry 6). With the
optimized reaction conditions in hand, we decided to investigate
the influence of reducing reagent (NaBH4) on the different protect-
ing groups (entries 6–10). In all cases TBDPS-protected amino acid
treated with NaBH4 in ethanol gave the best result with 92% yield
(entry 6). The stereochemistry of this compound was assigned by
analogy to the similar substrate.14
1
2
3
4
5
6
7
8
9
OTBDMS
OTBDMS
OTBDMS
OTBDMS
OTBDMS
OTBDPS
OTPS
OH
H
H
H
H
H
H
H
H
H
H
LiAlH4
Et2O
THF
—
DIBAL-H
NaBH3CN
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
NaBH4
23
36
53
70
92
65
70
68
85
EtOH
MeOH
EtOH
EtOH
EtOH
EtOH
EtOH
EtOH
OTBDMS
OTBDPS
10
using standard procedure to obtain mesylated product which was
converted into azide using NaN3 in DMF at 80 °C (Scheme 4). The
azide 10 was subjected to Pd/C catalyzed hydrogenation under
H2 atmosphere at room temperature to form amine, which was
easily protected with Cbz group using the standard procedure.
The last part of the synthesis of protected 4-mercapto-L-lysine con-
sists of introducing thiol unit into lysine chain. After deprotection
of the silyl ether 11 with tetra-butylammonium fluoride (TBAF),
the secondary alcohol of amino acid 12 was mesylated followed
by nucleophilic substitution of thioacetate to afford 13 in good
yield.15 Saponification and subsequent protection of 13 with S-
methyl methanethiosulfonate (MMTS) furnished 14, which was
then treated with TFA to get unprotected aminoacid (15) in good
yields. Further protection with Boc anhydride delivered the desired
amino acid 16.16 The unprotected amino acid 16 is useful interme-
diate for dual native chemical ligation.17
Accordingly, (2S,4S)-4-hydroxy-L-lysine 12 was useful precursor
to generate 4-substituted-L-lysine derivatives (Fig. 2) by using dif-
ferent nucleophiles, such as FÀ, BrÀ, and N3À. Similarly, enantiome-
Having the optimized reaction conditions, TBDPS-protected
substrate 9 was treated with methanesulfonyl chloride and DIPEA
rically pure minor product (7a) of Reformatsky reaction serves as a
NHBoc
CO2H
NH2
NHBoc
CHO
(i)
(ii)
HO
COOH
tBuO2C
tBuO2C
(iii)
O
4
5
6
Scheme 1. Reagents and conditions: (i) Ref. 8; (ii) EtSH, DCC, DMAP, DCM, rt, 95%; (iii) Et3SiH, 10% Pd/C, DCM, rt, 85%.
Boc
Boc
Boc
NH OH
NH OH
NH
(i)
CO2Me
CO2Me
CHO
+
tBuO2C
tBuO2C
tBuO2C
7b
7a
6
Scheme 2. Reagents and conditions: (i) methyl bromoacetate, Zn, TMSCl, THF, 0 °C, 92%.

6270
K. K. Pasunooti et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6268–6271
Boc
Boc
NH OTBDPS
NH OTBDPS
(i)
(iii)
(iv)
tBuO2C
N3
tBuO2C
OH
(ii)
9
10
Boc
Boc
NH OTBDPS
NH OH
(v)
(vi)
(vii)
tBuO2C
NHCbz
NHCbz
tBuO2C
NHCbz
11
12
Boc
Boc
SMe
(x)
(viii)
(ix)
NH SAc
NH
S
tBuO2C
tBuO2C
NHCbz
13
14
Boc
SMe
S
SMe
NH
NH2
S
(xi)
NHCbz
NHCbz
HO2C
HO2C
16
15
Scheme 4. Reagents and conditions: (i) methanesulfonyl chloride, diisopropyl ethylamine (DIPEA), 0 °C; (ii) NaN3, DMF, 80 °C, two steps 83% yield; (iii) Pd/C, ethyl acetate,
quantitative yield; (iv) CbzCl, NaHCO3, dioxane:water (2:1), 0 °C, 81%; (v) TBAF, THF, 0 °C, 77%; (vi) methanesulfonyl chloride, diisopropyl ethylamine (DIPEA), 0 °C; (vii)
potassium thioacetate, DMF, 40 °C, two steps 70% yield; (viii) NaOH, MeOH, rt; (ix) S-methyl methanethiosulfonate (MMTS), triethylamine, CH2Cl2, rt, 50% (two steps); (x) 95%
TFA, H2O, rt; (xi) Boc2O/TEA, MeOH, rt, 78% over two steps.
12. Selected reference on Reformatsky reaction: (a) Furstner, A. Synthesis 1989,
useful precursor for another potentially useful substrate for native
chemical ligation. Synthesis of these analogues is currently under
way in our laboratory.
571; (b) Rathka, M. W. Org. React. 1975, 22, 423; (c) Shriner, R. L. Org. React.
1942, 1, 1.
13. (2S,4R)-1-tert-Butyl 6-methyl 2-(tert-butoxy carbonyl amino)-4-hydroxy
hexanediote (7a)/(2S,4S)-1-tert-butyl 6-methyl-2-(tert-butoxy carbonyl amino)-
4-hydroxy hex anediote (7b): To a cooled (0 °C) solution of aldehyde (0.50 g,
In summary, a practical and concise synthesis of amino acid
(2S,4S)-4-mercapto-
commercially available
stereoselective Reformatsky reaction as a key step to form func-
tionalized -lysine derivatives. We believe that this approach
allows a direct access to 4-hydroxy- -lysine derivatives that offer
L-lysine has been developed starting from
1.83 mmol) in THF (7.32 mL, 0.25 M) was added dropwise
a solution of
L-aspartic acid. The synthesis involves dia-
Reformatsky reagent (4.57 mL, 4.57 mmol) (the experimental procedure for
Reformatsky reagent given below) over a period of 15 min and the reaction
mixture was stirred for 2 h. The reaction was quenched by the addition of
saturated, aqueous ammonium chloride solution and extracted three times
with ethyl acetate. The combined organic layers were then washed with
saturated sodium bicarbonate solution and brine, dried over sodium sulfate,
then concentrated in vacuo. The residue was purified by silica gel flash column
chromatography using ethyl acetate/hexane (20:80) as eluent. Rf (7a) = 0.28; Rf
(7b) = 0.34. Combined yield 92% (colorless solid). 7a [2S,4R] diastereomer: 1H
NMR (500 MHz, CDCl3): d in ppm = 5.38 (br s, 1H, NH), 4.20–4.18 (m, 2H, CH–
NH, CH–OH), 3.68 (s, 3H, CH3), 3.24 (br s, 1H, OH), 2.54–2.44 (m, 2H, CH2–
CO2Me), 1.94–1.86 (m, 2H, CH2), 1.44 (s, 9H, 3CH3), 1.41 (s, 9H, 3CH3); 13C NMR
(100 MHz, CDCl3): d in ppm = 172.8 (C@O), 171.5 (C@O), 155.5 (C@O), 82.0 (C),
79.8 (C), 65.2 (CH–OH), 51.9 (CH3), 51.7 (C–NH), 41.0 (CH2), 38.8 (CH2), 28.3
L
L
some interesting biologically active molecules and useful building
blocks for native chemical ligation.
Acknowledgments
We gratefully thank Nanyang Technological University and the
Ministry of Education, Singapore for the financial support.
À1
~
(3CH3), 27.9 (3CH3); IR (CHCl3):
m
= 3429, 3018, 2980, 2401, 1724, 1367 cm
;
HRMS (ESI): m/z: calcd for C16H30NO7: 348.2022 [M]+; found: 348.2021.
Compound 7b [2S,4S] diastereomer: 1H NMR (500 MHz, CDCl3):
d in
Supplementary data
ppm = 5.42 (d, J = 7.9 Hz, 1H, NH), 4.37–4.33 (m, 1H, CH–OH), 4.21 (d,
J = 3.5 Hz, 1H, CH-NH), 4.07 (br s, 1H, OH), 3.68 (s, 3H, CH3), 2.55 (dd, J = 15.7
and 8.1 Hz, 1H, CH–CO2Me), 2.40 (dd, J = 15.7 and 4.7 Hz, CH–CO2Me), 1.89–
1.84 (m, 1H), 1.61–1.54 (m, 1H), 1.44 (s, 9H, 3CH3), 1.41 (s, 9H, 3CH3); 13C NMR
(100 MHz, CDCl3): d in ppm = 172.1 (C@O), 171.6 (C@O), 156.7 (C@O), 82.3 (C),
80.4 (C), 64.4 (CH–OH), 51.7 (CH3), 51.2 (CH–NH), 41.2 (CH2), 40.6 (CH2), 28.2
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.bmcl.2009.09.107.
À1
~
References and notes
(3CH3), 27.9 (3CH3); IR (CHCl3):
m
= 3425, 3018, 2981, 2399, 1730, 1369 cm
;
HRMS (ESI): m/z: calcd for C16H30NO7: 348.2022 [M]+; found:
348.2033.Preparation of Reformatsky reagent (1 M solution in THF): A flame-
dried two-necked flask fitted with a reflux condenser and septum was charged
with zinc dust (0.47 g, 7.18 mmol), trimethylchlorosilane (TMSCl) (0.11 mL,
0.98 mmol), and dry THF (3.50 mL), then heated to reflux with stirring under
nitrogen for 15 min. The flask was then removed from the heat and methyl
bromoacetate (0.60 mL, 6.53 mmol) in dry THF (3.50 mL) was added via
syringe at such a rate as to maintain gentle reflux. At this stage the reaction
was stopped to allow the coarse Zn particles to settle down. The upper green
color solution (Reformatsky reagent, 1 M solution in THF) can be readily used
for further steps.
1. Hodgson, D. R. W.; Sanderson, J. M. Chem. Soc. Rev. 2004, 33, 422.
2. Haase, C.; Rohde, H.; Seitz, O. Angew. Chem., Int. Ed. 2008, 47, 6807.
3. Dawson, P. E.; Muir, T. W.; Clarklewis, I.; Kent, B. H. Science 1994, 266, 776.
4. Liu, C. F.; Tam, J. P. J. Am. Chem. Soc. 1994, 116, 4149.
5. Liu, C. F.; Tam, J. P. Proc. Natl. Acad. Sci. U.S.A. 1994, 91, 6584.
6. Payne, R. J.; Ficht, S.; Tang, S.; Brik, A.; Yang, Y. Y.; Case, D. A.; Wong, C. H. J. Am.
Chem. Soc. 2007, 129, 13527.
7. Hallinan, E. A.; Kramer, S. W.; Houdek, S. C.; Moore, W. M.; Gerome, G. M.;
Spanglar, D. P.; Stevens, A. M.; Shieh, H. S.; Manning, P. T.; Pitzele, B. S. Org.
Biomol. Chem. 2003, 1, 3527.
8. (a) Lachner, M.; Jenuwein, T. Curr. Opin. Cell Biol. 2002, 14, 286; (b) Spiro, R. G. J.
Biol. Chem. 1967, 242, 4813; (c) Van Slyke, D. D.; Hiller, A. Proc. Natl. Acad. Sci.
U.S.A. 1921, 7, 185.
9. Ramalingam, K.; Woodward, R. W. J. Org. Chem. 1988, 53, 1900.
10. Roberts, S. J.; Morris, J. C.; Dobson, R. C. J.; Gerrard, J. A. Bioorg. Med. Chem. Lett.
2003, 13, 265.
11. (a) Kameda, Y.; Nagano, H. Tetrahedron 2006, 62, 9751; (b) Chattopadhyay, A.;
Salaskar, A. Synthesis 2000, 561; (c) Bhalay, G.; Clough, S.; McLaren, L.;
Sutherland, A.; Willis, C. L. J. Chem. Soc., Perkin Trans. 1 2000, 901.
14. Martin, J.; Didierjean, C.; Aubry, A.; Casmir, J. R.; Briand, J. P.; Guichand, G. J.
Org. Chem. 2004, 69, 130.
15. Representative experimental procedures for compound 14 (2S, 4S)-tert-Butyl-
4-(acetylthio)-6-(benzyloxy carbonylamino)-2-(tertbutoxy carbonyl amino)
hexane –dioate: Compound 12 (0.05 g, 0.07 mmol) was dissolved in dry THF
(1.5 mL, 0.05 M) and cooled to 0 °C. 1 M solution of TBAF (0.11 mL, 0.11 mmol)
was introduced via syringe at the same temperature. The reaction mixture was
stirred for 8 h at 0 °C and quenched with saturated ammonium chloride
solution. Evaporation of the solvent gave a residue, which was dissolved in

K. K. Pasunooti et al. / Bioorg. Med. Chem. Lett. 19 (2009) 6268–6271
6271
ethyl acetate. The solution was washed with water and brine. The organic layer
was dried over sodium sulfate and concentrated in vacuo, which was purified
by silica column chromatography to give desired alcohol (0.025 g, 77%) as a
colorless oil. Then, 0.08 mL (0.44 mmol) of diisopropyl ethylamine (DIPEA) was
added to a solution of 0.10 g (0.22 mmol) of above alcohol in 2.2 mL (0.1 M) of
dichloromethane at room temperature. The solution was cooled to 0 °C, and
0.02 mL (0.27 mmol) of methanesulfonyl chloride was added. The reaction
mixture was allowed to reach room temperature and stirred for 2 h. The
reaction mixture was quenched with saturated ammonium chloride solution at
0 °C and diluted with dichloromethane. The layers were separated, the aqueous
layer was extracted with dichloromethane two times, and the combined
organic extract was washed with water and brine. Drying over anhydrous
sodium sulfate and removal of solvent under vacuum resulted in a colorless
oily residue which was dissolved in DMF (4.4 mL, 0.05 M). A total of 0.75 g
(0.66 mmol) of potassium thioacetate was added to the solution, which was
heated to 40 °C for 8 h. After allowed to reach room temperature, water was
added to the solution, which was extracted twice with ethyl acetate. The crude
product was purified by column chromatography on silica gel to give desired
product 14 (0.04 g, 70%) as a pale brown oil. 1H NMR (400 MHz, CDCl3): d in
ppm = 7.34–7.28 (m, 5H, Ph), 5.46 (br s, 1H, NH), 5.23 (d, J = 8.0 Hz, 1H, NH),
5.07 (dd, J = 14.8 and 12.5 Hz, 2H, CH2-Ph), 4.26 (dd, J = 13.6 and 7.8 Hz, 1H,
CH–NH), 3.66–3.59 (m, 1H, CH–S), 3.39 (dd, J = 13.0 and 5.4 Hz, 1H, CH2–NH),
3.15–3.10 (m, 1H, CH2–NH), 2.31 (s, 3H, CH3), 2.03 (dd, J = 13.4 and 6.5 Hz, 2H,
CH2), 1.90–1.82 (m, 1H, CH2), 1.68–1.59 (m, 1H, CH2) 1.44 (s, 9H, 3CH3), 1.40 (s,
9H, 3CH3); 13C NMR (100 MHz, CDCl3): d in ppm = 195.9 (COCH3), 171.1 (C@O),
156.4 (C@O), 155.6 (C@O), 136.7 (Ph), 128.4 (Ph), 128.1 (Ph), 127.9 (Ph), 82.4
(C), 80.1 (C), 66.5 (CH2-Ph), 51.9 (CH–NH), 39.7 (CH2–NH), 38.2 (CH2), 38.2
~
(CH2), 33.7 (CH–S), 33.7 (CH3) 28.2 (3CH3), 27.9 (3CH3); IR (CHCl3):
m = 3431,
3018, 2399, 1645, 2088, 1637, 1215 cmÀ1
; HRMS (ESI): m/z: calcd for
C25H39N2O7S: 511.2478 [M]+; found: 511.2480.
16. The white powder of Boc-lys(SSMe, Cbz)-OtBu 14 was dissolved in 0.5 mL of
95% TFA. After 1 h at room temperature, TFA was removed by evaporation to
get unprotected amino acid 15 in quantitative yield. The residue was dissolved
in 1 mL of methanol/H2O mixture (3:1). pH was adjusted to 8.0 with Et3N.
0.02 mL of Boc2O was added to react with 15 for 3 h at room temperature. The
mixture was subjected to semi-preparative HPLC isolation on C18 column. Boc-
Lys(SSMe, Cbz)-OH 15 (7 mg, 78% yield) was isolated. 1H NMR (400 MHz,
CDCl3): d in ppm = 7.34–7.33 (m, 5H, Ph), 5.33 (br s, 1H, NH), 5.29 (d, J = 7.2 Hz,
1H, NH), 5.08 (s, 2H, CH2-Ph), 4.43 (b, 1H, CH–NH), 3.38 (b, 2H, CH2), 2.92–2.86
(m, 1H, CH), 2.38 (s, 3H, CH3), 2.17–2.03 (m, 2H, CH2), 1.87–1.83 (m, 2H, CH2)
1.39 (s, 9H, 3CH3). 13C NMR (100 MHz, CDCl3): d in ppm = 175.3 (C@O), 156.7
(C@O), 156.0 (C@O), 136.4 (Ph), 128.4 (Ph), 128.2 (Ph), 128.1 (Ph), 80.8 (C), 66.8
(CH2-Ph), 51.4 (CH–NH), 44.7 (CH2–NH), 39.1 (CH3–S), 38.5 (CH2), 32.6 (CH2),
À1
~
m
28.2 (3CH3), 24.0 (CH-S). IR (CHCl3):
= 3440, 3022, 2399, 1650, 1640 cm
.
HRMS (ESI): m/z: calcd for C20H30N2O6S2Na: 481.1443; [M+Na]+; found
481.1446.
17. Yang, R.; Pasunooti, K. K.; Li, F.; Liu, X. W.; Liu, C. F. J. Am. Chem. Soc. 2009, 131,
13592.