An efficient deprotection of N-trimethylsilylethoxymethyl (SEM) groups from dinucleosides and dinucleotides

Article abstract of DOI:10.1080/15257771003612847

A convenient and efficient method for deprotection of N-(trimethyl) silylethoxymethyl (SEM) groups from thymidine dinucleoside and dinucleotide has been achieved. The SEM groups were easily removed in excellent yields from protected nucleosides, dinucleosides, and dinucleotides.

Full text of DOI:10.1080/15257771003612847

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An Efficient Deprotection of N-
Trimethylsilylethoxymethyl (SEM) Groups
From Dinucleosides and Dinucleotides
Tilak Chandra a , William E. Broderick a & Joan B. Broderick a
a Department of Chemistry and Biochemistry , Montana State
University , Bozeman, Montana, USA
Published online: 24 Feb 2010.
To cite this article: Tilak Chandra , William E. Broderick & Joan B. Broderick (2010) An Efficient
Deprotection of N-Trimethylsilylethoxymethyl (SEM) Groups From Dinucleosides and Dinucleotides,
Nucleosides, Nucleotides and Nucleic Acids, 29:2, 132-143, DOI: 10.1080/15257771003612847
To link to this article: http://dx.doi.org/10.1080/15257771003612847
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Nucleosides, Nucleotides and Nucleic Acids, 29:132–143, 2010
Copyright ꢀC Taylor and Francis Group, LLC
ISSN: 1525-7770 print / 1532-2335 online
DOI: 10.1080/15257771003612847
AN EFFICIENT DEPROTECTION OF
N-TRIMETHYLSILYLETHOXYMETHYL (SEM) GROUPS FROM
DINUCLEOSIDES AND DINUCLEOTIDES
Tilak Chandra, William E. Broderick, and Joan B. Broderick
Department of Chemistry and Biochemistry, Montana State University,
Bozeman, Montana, USA
A convenient and efficient method for deprotection of N-(trimethyl)silylethoxymethyl (SEM)
2
groups from thymidine dinucleoside and dinucleotide has been achieved. The SEM groups were
easily removed in excellent yields from protected nucleosides, dinucleosides, and dinucleotides.
Keywords Dinucleosides; spore photoproduct; S-adenosylmethionine; spore photo-
product lyase
SAM; S-adenosylmethionine; SPL, spore photoproduct lyase; SP, spore photoproduct;
TES, triethylsilyl; TBDMS, tert-butyldimethylsilyl.
INTRODUCTION
The trimethylsilylethoxymethyl (SEM) group is frequently used for the
protection of alcohols and amines for the synthesis of carbohydrates and nat-
ural products.[1,2] The trimethylsilylethoxymethyl group easily survives under
bromination, basic hydrolysis, oxidation and other harsh conditions.[3] SEM
groups can be removed from protected heterocycles or nitrogen contain-
ing compounds using hydrochloric acid under refluxing conditions[4] or at
elevated temperature,[5] while SEM protecting groups on nucleosides have
been removed using tin tetrachloride at low temperature.[3] Magnesium bro-
mide[6,7] in ether or nitromethane has proven a useful combination for the
deprotection of SEM ethers in the presence of sensitive groups such as tert-
butyldimethylsilyl (TBS) and triisopropylsilyl (TIPS). Neat tetrabutylammo-
nium fluoride[8] works well for N-SEM deprotection in some cases, with the
Received 14 December 2009; accepted 12 January 2010.
This work has been supported by the National Institutes of Health (GM67804 to J.B.B.).
Address correspondence to Joan B. Broderick, Department of Chemistry and Biochemistry, Montana
State University, Bozeman, MT 59717, USA. E-mail: jbroderick@chemistry.montana.edu
132

Deprotection of SEM Groups
133
FIGURE 1 5R and 5S-SP with and without a phosphate backbone.
rate of deprotection depending upon the degree of vacuum. In general, how-
ever, SEM deprotection from alcohols seems facile[9–14] whereas the N-SEM
deprotection is frequently problematic.
During the course of our studies on the synthesis of spore photoproduct
(SP)[15,16] and derivatives (Figure 1) for mechanistic studies of the DNA re-
pair enzyme SPL, we became interested in the efficient deprotection of SEM
groups to accomplish optimum yields of the final product. SPL is a radical
S-adenosylmethionine (AdoMet) enzyme that utilizes an iron-sulfur cluster
and AdoMet to to generate a putative 5ꢁ-deoxyadenosyl radical intermediate,
which abstracts a hydrogen atom from C-6 of SP to initiate a radical-mediated
β-scission.[17–20] Our recent work on the synthesis and repair of spore pho-
toproduct using spore photoproduct lyase provides direct evidence for the
stereochemical requirements of spore photoproduct repair by spore product
lyase (SPL), with only the 5R-stereoisomers (dinucleosides/dinucleotide)
acting as substrates (Figure 2).[21,22] Our need for pure SP substrate for
mechanistic studies has led us to develop methods for the synthesis of
stereochemically-defined dinucleoside and dinucleotide SP substrates.[21–23]
The complete multistep synthesis of 5R and 5S-spore photoproducts
from thymidine involves the condensation of dihydrothymidine and
thymidine, selective deprotection of triethylsilyl groups,[23] phosphorylation

134

Deprotection of SEM Groups
135
TABLE 1 Yields of 5R and 5S-SP using tin tetrachloride
O
N
O
N
O
N
Me
O
N
Me
SEM
SEM
N
NH
N
HN
O
SnCl4, 0 oC
O
O
H
O
H
H
H
O
O
O
O
OR1
OR1
OR1
OR1
R1O
R1O
OR1
OR1
5R/5S
5R/5S
Entry
Compound
5R/5S
R1
Reagent
Yields
1
2
3
4
5
6
1
3
5
6
14
9
5R
5R
5S
5S
H
Ac
H
Ac
Ac
Ac
SnCl4
SnCl4
SnCl4
SnCl4
SnCl4
SnCl4
45–55
98
40–50
95
93
95–98
Thymidine
5R
at the 3ꢁ hydroxyl of dihydrothymidine and phosphodiester bond formation
between dihydrothymidine and thymidine. Only a few methods are re-
ported for deprotecting the N -SEM from nucleosides and nucleotides; these
proved unsatisfactory for the deprotection of N-SEM from SP dinucleosides
and dinucleotides (Table 1), and led us to develop the alternate method
described here.
RESULTS AND DISCUSSION
The dinucleosides of protected thymidine (5R and 5S-diastereomers)
were prepared by coupling N 3-trimethylsilylethoxymethyl-3, 5-di-triethylsilyl-
5,6-dihydrothymidine and 2-bromomethyl uridine using lithium diisopropyl
amide (LDA) as a condensing reagent at −78◦C, which afforded 5R and 5S-
diastereomers in excellent yields.[21,23] The 5R and 5S-diastereomers were
purified on a silica gel column using a gradient of ethyl acetate and hex-
anes. The stereochemistry of protected dinucleosides was determined by
two-dimensional Nuclear Overhauser Enhancement Spectroscopy (NOESY)
and Rotating-frame Overhauser Effect Spectroscopy (ROESY).[21] In the
next step the tert-butyldimethylsilyl (TBDMS) and triethylsilyl (TES) groups
were removed using HF:pyridine at room temperature in good yields to
produce the di-SEM protected 5R (1) and 5S-dinucleosides (5).[23]
Initial attempts at deprotecting compound 1 were based on literature
protocols and involved treating with tin tetrachloride at 0◦C; this resulted in
only a 40–50% yield of the desired product (Scheme 1, Table 1). A major side

136
T. Chandra et al.
SCHEME 1 Deprotection of N-SEM from 5R-SP using literature protocol.
product was a polar species that did not show any significant nuclear mag-
netic resonance (NMR) signals; mass analysis demonstrated that the polar
species are comprised of tin complexed with the dinucleoside. As such com-
plexation would most likely occur through the sugar hydroxyl groups, we
deduced that protection of these hydroxyl groups might improve the yield
in SEM deprotection. The sugar hydroxyls were thus protected using acetic
anhydride and pyridine at ambient temperature with high purity and yields
(Schemes 2 and 3). The structures of these fully protected dinucleosides
(3 and 6) were easily deduced using one- and two-dimensional NMR tech-
niques. Once the 3ꢁ,5ꢁ- hydroxyls were protected, the SEM groups were easily
SCHEME 2 Deprotection of N-SEM from 5R-SP dinucleoside with protected hydroxyls.

Deprotection of SEM Groups
137
SCHEME 3 Deprotection of N-SEM from 5S-SP dinucleoside with protected hydroxyls.
removed from the dinucleosides in excellent yields (Table 1) to produce
4 and 7. Finally, the acetates were removed using ammonium hydroxide at
ambient temperature to afford the desired 5R- and 5S-spore photoproducts
2 and 8. NMR and mass spectroscopy (MS) analysis confirmed the structure
of the final 5R- and 5S-SP.
To check the validity of the reaction, the acetate protected phospho-
triester[3,21,22] was also treated with tin tetrachloride under similar reaction
conditions as described above and afforded the SEM deprotected product
in 95–98% yields (Scheme 4). The SEM from 3ꢁ and 5ꢁ acetate protected
thymidine 14 was also deprotected (Scheme 5) in excellent yields (93%)
in a similar fashion as described for the thymine dinucleosides. Finally, the
efficacy of this method is illustrated by our ability to use the fully depro-
tected synthetic dinucleoside spore photoproducts in SPL activity assays,
SCHEME 4 Deprotection of N-SEM from protected phosphotriester.

138
T. Chandra et al.
SCHEME 5 Deprotection of N-SEM from protected thymidine.
which clearly showed that only the 5R diastereomer was repaired by
SPL.[21]
EXPERIMENTAL
All reactions were carried out in oven- or flame-dried glassware under a
nitrogen atmosphere. Solvents were distilled prior to use. Dichloromethane
and pyridine were distilled from calcium hydride. Purification of reac-
tion products was carried out by flash chromatography using silica gel
(230–400 mesh). All reagents were commercially available and used with-
out further purification. All reactions were monitored by thin-layer chro-
matography (TLC) using silica gel 60, F-254. Column chromatography was
conducted using flash silica gel. 1H NMR and 13C NMR spectra were recorded
on a Bruker DPX-300, Bruker DRX-500 or on a Bruker DRX-600 (Brucker,
Billerica, MA, USA). NMR spectra were recorded on solutions in deuterated
1
chloroform (CDCl3), with residual chloroform (δ 7.27 ppm for H NMR
and δ 77.0 ppm for 13C NMR) or deuterated dimethyl sulfoxide (DMSO-d6),
1
with residual dimethyl sulfoxide (δ 2.50 ppm for H NMR and δ 35.0 ppm
for 13C NMR) taken as the standard, and were reported in parts per million
(ppm). Abbreviations for signal coupling are as follows: s, singlet; d, doublet;
t, triplet; q, quartet; m, multiplet. The multiplicities of the 13C NMR signals
were determined by heteronuclear multiple quantum coherence (HMQC)
and distortionless enhancement by polarization transfer (DEPT) techniques.
Mass spectra (high resolution FAB [fast-atom bombardment] or ESI [electro
spray ionizations]) were recorded on a Q-Tof and 70-VSEs spectrometer at
Noyes Laboratory, University of Illinois Urbana-Champaign.
General
Tetra Acetate Formation of Thymidine Dinucleoside
A solution of 1 or 521 (0.100 g, 0.13 mmol) in pyridine (5.0 mL) and
acetic anhydride (1.0 mL) was stirred at room temperature for 5 hours. After

Deprotection of SEM Groups
139
complete acetylation the solvent was removed on a rotary evaporator under
reduced pressure. The residue was dissolved in methylene chloride and
washed with saturated sodium bicarbonate solution. The methylene chloride
layer was dried over anhydrous sodium sulfate, concentrated and finally the
residue was purified on a silica gel column (flash chromatography) using a
mixture of ethyl acetate:hexanes (50:50), resulting in the desired product as
a white fluffy solid with 90–95% yield.
Deprotection of N-SEM from Protected Thymidine Dinucleoside
To a cold solution of protected dinucleoside 3 or 6 (100 mg, 0.11 mmol)
in methylene chloride (10 mL), tin tetrachloride 1M (1.5 mL) in methy-
lene chloride (5.0 mL) was added dropwise over 25 minutes. The reaction
mixture was stirred at 0◦C for 1 hour, and then at room temperature for
an additional 1 hour. The reaction progress was monitored using TLC. Af-
ter completion of the reaction, the solution was cooled and the reaction
mixture was neutralized with 4% sodium hydroxide (5.0 mL). The mixture
was stirred for 10 minutes, and the solid was removed by centrifugation and
the organic layer was decanted and the solvent was removed under reduced
pressure. The residue was purified on a silica gel column using a mixture
of 5% methanol and methylene chloride, which afforded SEM deprotected
dinucleosides in 95–98% yield.
(5R-Tetra acetate 3): Yield: 95%; viscous oil; Rf. 0.5; 1H NMR (CDCl3): δ
-0.053 (s, 9H, CH3), -0.034 (s, 9H, 3CH3), 0.80–0.885 (m, 2H, CH2), 0.91 (t,
J = 8 Hz, 2H, CH2, SEM), 1.19 (s, 3H, Me), 1.96–2.34 (m, 4H, CH2, 2ꢁ), 2.0
(s, 3H, OAc), 2.07 (s, 3H, OAc), 2.19 (s, 3H, OAc), 2.2 (s, 3H, OAc), 2.61 (d,
J = 14.5 Hz, 1H, CH2, bridge), 2.79 (d, J = 14.5 Hz, 1H, CH2, bridge), 3.10
(d, J = 13Hz, 1H, CH2, base), 3.23 (d, J = 13 Hz, 1H, CH2, base), 3.54 (t,
2H, J = 8 Hz, CH2, SEM), 3.62 (t, J = 8 Hz, 2H, CH2, SEM), 4.09 (q, 1H, CH,
4ꢁ), 4.20 (q, 1H, 4ꢁ), 4.25 (bs, 1H, 3ꢁ), 4.26 (bs, 1H, 3ꢁ), 4.30 (dd, J = 3.5, 8.5
Hz, 2H, CH2, 5ꢁ), 4.35 (dd, J = 3.5, 8.5 Hz, 2H, CH2, 5ꢁ), 5.11–5.31 (m, 4H,
NCH2, SEM), 6.28–6.34 (m, 2H, 1ꢁ), 7.58 (s, 1H, base); 13C NMR (CDCl3): δ
−1.43 (CH3), 18.0 (CH2), 18.1 (Cquat), 20.81 (Me, OAc), 20.86 (Me, OAc),
20.87 (Me, OAc), 20.97 (Me, OAc), 22.43 (CH3, C-5), 32.3 (CH2 bridge),
33.7 (CH2), 37.1 (CH2), 42.2, 43.6 (CH2-base), 63.7 (CH2), 63.9 (CH2), 66.8
(CH2), 67.69 (CH2), 70.0 (CH2, SEM), 70.4 (CH2, SEM), 80.7 (C 3ꢁ), 82.0
(C 3ꢁ), 84.3 (C 4ꢁ), 85.0 (C, 1ꢁ), 108.9 (Cquat), 139.1 (CH), 150.6 (Cquat),
152.2 (Cquat), 163.4 (Cquat), 170.2 (Cquat); 170.4 (Cquat), 170.7 (Cquat),
170.8 (Cquat), 173.7 (Cquat); MS: (TOF, MS, ESI) m/z 935 (M + Na).
1
(Compound 4): Yield: 98%; viscous oil; Rf. 0.4; H NMR (CD3OD): δ
1.16 (s, 3H, Me), 2.03 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.11 (s, 3H, OAc),
2.4 (s, 3H, OAc), 2.10–2. 18 (m, 4H, CH2, 2ꢁ), 2.64–2.71 (m, 2H, CH2,
bridge), 3.21–3.31 (m, 2H, C-6), 4.07 (bt 1H, 4ꢁ), 4.17–4.38 (m, 5H, 4ꢁ,
5ꢁ), 5.13 (bt, 1H, 3ꢁ), 5.23 (bt, 1H, 3ꢁ), 6.18–6.24 (m, 2H, 1ꢁ), 7.57 (s, 1H,

140
T. Chandra et al.
base); 13C NMR (CD3OD): δ 21.05 (CH3), 22.1 (OAc), 32.31 (CH2), 34.34
(CH2), 38.0 (CH2), 43.92 (Cquat), 46.6 (CH2-base), 65.16 (CH2), 75.7,
76.18, 82.28, 83.61, 85.41, 86.32, 91.2, 111.0 (Cquat), 141.17 (CH), 152.1
(Cquat), 154.37 (Cquat), 166.2 (Cquat), 172.29 (Cquat), 172.3 (Cquat),
172.6 (Cquat), 172.78 (Cquat), 176.5 (Cquat); MS: (TOF, MS, ESI) m/z 653,
652, 325, 326.
(5S-Tetra acetate 6): Yield: 90%; viscous oil; Rf. 0.5; 1H NMR (CDCl3): δ
−0.058 (s, 9H, CH3), −0.041 (s, 9H, 3CH3), 0.81–0.92 (m, 4H, CH2, SEM),
1.17 (s, 3H, Me), 1.94–2.18 (m, 2H, CH2, 2ꢁ), 2.0 (s, 3H, OAc), 2.07 (s,
3H, OAc), 2.19 (s, 3H, OAc), 2.2 (s, 3H, OAc), 2.41 (dd, 2H, CH2, 2ꢁ),
2.64 (d, J = 14.5 Hz, 1H, CH2, bridge), 2.70 (d, J = 14.5 Hz, 1H, CH2,
bridge), 3.10–3.16 (m, 2H, CH2, base), 3.48–3.54 (m, 2H, CH2), 3.6 (t, 2H,
J = 8 Hz, CH2, SEM), 4.06 (q, 1H, CH, 4ꢁ), 4.1 (q, 1H, 4ꢁ), 4.2 (bs, 1H, 3ꢁ),
5.11–5.31 (m, 4H, NCH2, SEM), 6.26–6.29 (m, 1H, 1ꢁ), 6.34–6.37 (m, 1H,
1ꢁ), 7.47 (s, 1H, base); 13C NMR (CDCl3): δ −1.43 (CH3), 18.0 (CH2), 18.1
(CH2), 20.9 (Me, OAc), 21.6 (CH3, C5), 32.31 (CH2 bridge), 33.9 (CH2),
37.4 (CH2), 42.6 (Cquat, C-5), 44.4 (CH2-base), 64.0 (CH2), 66.8 (CH2),
67.5 (CH2), 70.1 (CH2), 70.4 (CH2, SEM), 74.4 (CH), 74.44 (CH), 80.6 (C
3ꢁ), 82.1, 84.5 (C 4ꢁ), 85.6 (C, 1ꢁ), 109.0 (Cquat), 137.6 (CH), 150.5 (Cquat),
152.7 (Cquat), 163.2 (Cquat), 170.3 (Cquat); 170.4 (Cquat), 170.42 (Cquat),
170.53 (Cquat), 173.2(Cquat); MS: (TOF, MS, ESI) m/z 913.
1
(Compound 7): Yield: 88%; viscous oil; Rf. 0.4; H NMR (Acetone-d6):
δ 1.1 (s, 3H, Me), 2.04 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.08 (s, 3H, OAc),
2.1 (s, 3H, OAc), 2.29–2.45 (m, 4H, CH2, 2ꢁ), 2.5 (d, J = 14 Hz, 1H, CH2,
bridge), 2.75 (d, J = 14 Hz, 1H, CH2, bridge), 3.2 (q, 2H, CH2, base), 3.51
(m, 2H, CH2, C5ꢁ), 4.0 (bt, 1H, 4ꢁ), 4.17–4.38 (m, 3H, 4ꢁ, 5ꢁ), 5.0 (bt, 1H,
3ꢁ), 5.23 (bt, 1H, 3ꢁ), 6.2–6.3 (m, 2H, 1ꢁ), 7.5 (s, 1H, base), 9.15 (s, 1H, NH),
10.1 (s, 1H, NH); 13C NMR (Acetone-d6): δ 21.0 (CH3), 21.1 (OAc), 32.2
(CH2), 34.2 (CH2), 37.6 (CH2), 43.2 (Cquat), 46.8 (CH2-base), 64.8 (CH2),
75.4, 75.6, 81.6, 83.0, 85.0, 85.9, 110.4 (Cquat), 139.7 (CH), 151.0 (Cquat),
153.2 (Cquat), 164.5 (Cquat), 170.8 (Cquat), 171.0 (Cquat), 174.7 (Cquat);
MS: (TOF, MS, ESI) m/z 653, 652, 325, 326.
(Compound 8): A solution of 7 (0.08 g, 0.12 mmol) in ammonium hy-
droxide (∼26%) was kept at room temperature for 24 hours. After complete
deprotection of chlorophenyl and acetate, the excess ammonium hydroxide
was removed under reduced pressure. The residue was partitioned between
methylene chloride and water. The water layer was separated and carefully
washed with methylene chloride. The aqueous layer was concentrated on
a rotary evaporator under reduced pressure, which afforded the pure 5S-
1
SP without any further purification. Yield: 85–95%; white solid; Rf. 0.2; H
NMR (500 MHz, DMSO-d6): δ 1.0 (s, 3H, Me), 1.75–1.79 (m, 2H, CH2, 2ꢁ),
1.96–2.01 (m, 2H, CH, 2ꢁ), 2.25 (d, J = 14 Hz, 1H, CH2, bridge), 2.71 (d,
J = 14 Hz, 1H, CH2 bridge), 3.05 (d, J = 13 Hz, 1H, CH2 bridge), 3.19 (d,
J = 13 Hz, 1H, CH2 bridge), 3.2–3.6 (m, 4H, CH2, 5ꢁ), 3.61 (m, 1H, 4ꢁ), 3.7

Deprotection of SEM Groups
141
(q, 1H, J = 3.5 Hz, CH, 4ꢁ), 4.24 (bt, J = 3.5 Hz, 1H, 3ꢁ), 4.34–4.36 (bt, J = 3.5
Hz, 1H, 3ꢁ), 4.7 (t, 1H), 4.9 (t, 1H), 5.1 (d, 1H), 5.2 (d, 1H), 6.1 (t, J = 7 Hz,
1H, 1ꢁ), 6.15 (t, J = 6.5 Hz, 2H, 1ꢁ), 7.6 (s, 1H, base, C-6), 10.1 (s, 2H, NH);
13C NMR (DMSO-d6): δ 20.5 (CH3), 32.6 (CH2), 37.6 (CH2), 41.34 (CH2),
43.4 (Cquat), 47.9 (CH2-base), 63.1 (CH2, 5ꢁ), 63.6 (CH2, 5ꢁ), 72.4 (3ꢁ), 72.7
(3ꢁ), 85.4 (C 4ꢁ), 86.6 (C 1ꢁ), 87.6 (C 4ꢁ), 89.0 (C 1ꢁ), 110.6 (Cquat), 141.4
(CH), 152.2 (Cquat), 154.6 (Cquat), 166.3 (Cquat), 176.4 (Cquat); MS: m/z
507 (M + Na); HRMS: m/z: 485.1893 (calcd. for C20H29N4O10; 485.1884)
(M + H).
(Compound 11): Yield: 80–90%; white solid; Rf. 0.1; 1H NMR (CD3OD): δ
1.24 (s, 3H, Me), 2.1 (dd, 1H, CH2, 2ꢁ), 2.2–2.9 (m, 1H, CH, 2ꢁ), 2.3–2.38 (m,
1H, CH, 2ꢁ), 2.4–2.49 (m, 1H, CH, 2ꢁ), 2.60 (d, J = 14 Hz, 1H, CH2, bridge),
2.8 (d, J = 14 Hz, 1H, CH2, bridge), 3. 3 (d, J = 14 Hz, 1H, CH2, base), 3.4
(d, J = 13.5 Hz, 1H, CH2, base), 3.62–3.67 (m, 2H, CH2, 5ꢁ), 3.7 (dd, J = 3.5,
10 Hz, 2H, CH2, 5ꢁ), 3.9 (bt, 1H, CH, 4ꢁ), 4.0 (bs, 1H, 4ꢁ), 4.5–4.53 (m, 1H,
3ꢁ), 4.6–4.67 (m, 1H, 3ꢁ), 6.1–6.17 (m, 2H, 1ꢁ), 7.8 (s, 1H, base); 13C NMR
(CD3OD): δ 24.2 (CH3, C5), 36.5 (CH2 bridge), 37.2 (CH2), 39.9 (CH2),
41.9, 47.3 (CH2-base), 61.5 (CH2), 65.2 (CH2), 71.2 (C 3ꢁ), 73.2 (C 3ꢁ), 83.8
(C 4ꢁ), 84.3 (C, 1ꢁ), 85.2 (C 1ꢁ), 86.5 (C 4ꢁ), 112.0 (Cquat), 140.1 (CH), 152.5
(Cquat), 155.5 (Cquat), 165.4 (Cquat), 176.9 (Cquat); 31P NMR (CD3OD):
0.064; HRMS: m/z: 547.1420 (calcd. for C20H28N4O12P; 547.1441) (M + H);
MS: (TOF, MS, ESI) m/z 547, 449, 362, 314.
(Compound 13): Yield: 95%; white solid; Rf. 0.5; 1H NMR (CDCl3): δ 1.8
(s, 3H, Me), 2.0 (s, 3H, OAc), 2.1 (s, 3H, CH3), 2.2–2.3 (m, 1H, CH, 2ꢁ),
2.4–2.5 (m, 1H, CH, 2ꢁ), 4.27 (m, 1H, CH), 4.3 (m, 2H, CH2, 5ꢁ), 5.2 (m, 1H,
3ꢁ), 6.3 (m, 2H, 1ꢁ), 7.3 (s, 1H, base), 7.3 (s, 1H, base); 13C NMR (CD3OD):
δ 12.7 (CH3, C5), 20.86 (OAc), 20.94 (OAc), 37.5 (CH2), 63.9 (CH2), 74.1
(C 3ꢁ), 82.1 (C 4ꢁ), 84.8 (C, 1ꢁ), 111.6 (Cquat), 134.5 (CH), 150.5 (Cquat),
163.7 (Cquat), 170.2 (Cquat), 170.49.
(Compound 14): Yield: 90–95%; viscous oil; Rf. 0.7; 1H NMR (CDCl3): δ
0.9 (s, 9H, TMS), 0.9 (t, 2H, CH2, SEM), 1.9 (s, 3H, Me), 2.0 (s, 3H, OAc),
2.1 (s, 3H, OAc), 2.2–2.3 (m, 1H, CH, 2ꢁ), 2.3–2.4 (m, 1H, CH, 2ꢁ), 3.6 (t,
2H, SEM), 4.1 (m, 1H, CH), 4.3 (m, 2H, CH2, 5ꢁ), 5.2 (m, 1H, 3ꢁ), 5.28 (s,
2H, SEM), 6.2 (m, 2H, 1ꢁ), 7.23 (s, 1H, base); 13C NMR (CDCl3): δ –1.43
(SEM), 13.3 (CH3, C5), 18.1 (SEM), 20.8 (OAc), 20.88 (OAc), 37.5 (CH2),
63.8 (CH2), 67.5, 70.2, 74.0, 82.1, 82.1 (C 4ꢁ), 85.4 (C, 1ꢁ), 110.7 (Cquat),
133.2 (CH), 150.8 (Cquat), 163.1(Cquat), 170.1 (Cquat), 170.3 (Cquat).
CONCLUSION
In summary, we illustrate a simple and convenient methodology for the
deprotection of SEM, (trimethylsilyl)ethoxymethyl from thymidine, thymi-
dine dinucleosides and dinucleotides to the subsequent amines in excellent
yields. SEM groups from the protected dinucleosides can be removed in

142
T. Chandra et al.
95–98% yields; while the same groups from unprotected dinucleosides pro-
duces low yields of the desired product. In addition, the acetate protected
5R and 5S-dinucleosides were easily deprotected into corresponding 5R and
5S-spore photoproduct.
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