Synthesis of some new s-nucleoside derivatives of 2-thioxo and (2,4-Dithioxo)-5,6,7,8-Tetrahydrobenzo-Thieno[2,3-d]Pyrimidin-4-(3H)Ones

Article abstract of DOI:10.1080/10426500903147159

Ribosylation of 2-thioxo-5,6,7,8-tetrahydrobenzo thieno[2,3-d]pyrimidin- 4(3H)-one 1a and 2,4-dithioxo-5,6,7,8-tetrahydrobenzo thieno[2,3-d]pyrimidine 1b with 1-O-acetyl-2,3,5-tri-O-benzoyl - D-ribofuranose 7 afforded the benzoylated S-nucleoside derivati

Full text of DOI:10.1080/10426500903147159

Phosphorus, Sulfur, and Silicon, 185:1615–1622, 2010
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426500903147159
SYNTHESIS OF SOME NEW S-NUCLEOSIDE
DERIVATIVES OF 2-THIOXO AND
(2,4-DITHIOXO)-5,6,7,8-TETRAHYDROBENZO-THIENO[2,3-
d]PYRIMIDIN-4-(3H)ONES
Laila M. Break,1 Nadia A. M. M. Shmiss,2
and Mosselhi A. N. Mosselhi3
1Department of Chemistry, Faculty of Science (Girls), Taif University, Taif,
Saudi Arabia
2Department of Chemistry, Faculty of Science (Girls), University of Azhar,
Cairo, Egypt
3Department of Chemistry, Faculty of Science, Taif University, Taif, Saudi Arabia
Ribosylation of 2-thioxo-5,6,7,8-tetrahydrobenzo thieno[2,3-d]pyrimidin-4(3H)-one 1a and
2,4-dithioxo-5,6,7,8-tetrahydrobenzo thieno[2,3-d]pyrimidine 1b with 1-O-acetyl-2,3,5-tri-
O-benzoyl-β-D-ribofuranose 7 afforded the benzoylated S-nucleoside derivatives 3 and 4,
respectively. Debenzoylation of 3 and 4 by using methanolic sodium methoxide yielded
the corresponding free S-nucleosides 5 and 6, respectively. Furthermore, the reaction of
potassium salt of 2-thioxo-5,6,7,8-tetrahydrobenzo thieno[2,3-d]pyrimidin-4(3H)-one 8 with
2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 9, afforded 10. Deacetylation of the latter
by using methanolic sodium methoxide yielded the corresponding S-glycoside, 2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-
tetra-hydroxy-β-D-glucopyranosylthio)-5,6,7,8-tetrahydro-benzothieno [2,3-d]pyrimidin-4-
one 11. The structural elucidation of the new nucleosides formed was reported.
Keywords 1-O-Acetyl-2,3,5-tri-O-benzoyl-β-D-ribo-furanose; 2,4-dithioxo-benzothieno[2,3-
d]pyrimidine; S-glycosides; 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide; 2-thioxo-
benzothieno[2,3-d]pyrimidin-4(3H)-one
INTRODUCTION
Thieno[2,3-d]pyrimidines have a special position among fused pyrimidines because
they are structural analogues of biogenic purines and can be considered as potential nucleic
acid antimetabolites. Their derivatives have been reported to have remarkable activity, e.g.,
antifungal, antibacterial, insecticidal, hypnotic, antiallergic, and antiviral activity.1,2,13–17 In
addition, some interesting compounds exhibit moderate anti-HIV-1 potency and antitumor
activity when the thiophene moiety is fused to a carbocyclic ring.3,18
Derivatives containing the thieno[2,3-d]pyrimidine nucleosides have been reported to
possess several important pharmacological properties; in particular the biological activity
of some thieno[2,3-d]pyrimidine nucleosides as antiviral agents against HIV-1 and herpes
simplex virus (HSV-1) has been reported.4,5
Received 10 May 2009; accepted 26 June 2009.
Address correspondence to Mosselhi A. N. Mosselhi, Department of Chemistry, Faculty of Science, Taif
University, P. O. 888, Taif, Saudi Arabia. E-mail: mosselhi2008@hotmail.com
1615

1616
L. M. BREAK ET AL.
Other differently substituted thieno[2,3-d]pyrimidine nucleosides as antiviral agents
against hepatitis-A virus (HAV) have been recently described.6 In light of these consider-
ations and in continuation of the studies in the chemistry of nucleosides and thieno[2,3-
d]pyrimidine,7–12,22–24 we thought it interesting to investigate the synthesis of some new
nucleosides of thieno[2,3-d]pyrimidine.
RESULTS AND DISCUSSION
The starting compounds, 2-thioxo-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidin-
4(3H)-one (1a) and 2,4-dithioxo-5,6,7,8-tetrahydrobenzothieno[2,3-d]pyrimidine (1b)
were prepared as reported in the literature19 from the reaction of 2-amino-4,5,6,7-
tetrahydrobenzo-thiophene-3-[carbo(thio)oxamide] with carbondisulfide. Ribosylation of
1a,b was achieved by refluxing in hexamethyldisilazane (HMDS) to give the silylated
derivatives 2a,b. The latter was stirred with 1-O-acetyl-2,3,5-O-benzoyl-β-D-ribofuranose
(7) in the presence of 1,2-dichloroethane as solvent using trimethylsilyl trifluoromethane-
sulfonate (TMS triflate) as a catalyst for 24 h (followed by TLC), following the method
of Vorbruggen et al.,20 to give the corresponding β-anomeric protected S-nucleoside
derivatives 3 and 4, respectively, in good yields (Scheme 1).
Debenzoylation of 3 and 4 was performed by using methanolic sodium methox-
ide solution following Zemplen et al.’s method21 to afford the free nucleosides 5 and 6,
respectively (Scheme 1).
The chemical structures of nucleoside derivatives 3–6 were established and confirmed
on the basis of their elemental analyses and spectral data (IR, 1H and 13C NMR) (see the
Experimental section). 1H NMR spectra of 3 and 4 showed in each case a doublet signals at
δ 6.5 for compound 3 and at δ 6.3, 6.4 for compound 4 assigned to the anomeric proton of the
ꢁ
ꢁ
ribose moiety with spin–spin coupling constant (J1 ,2 ) equal to 5.5 Hz, which confirms the
β-anomeric configuration. This is in accord with the results for other 2,3,5-tri-O-benzoyl-
1-β-D-furanosyl pyrimidine and purine nucleosides.20,22–24
The 13C NMR of nucleoside products revealed the absence of a thione carbon atom
at about δ 173.0 for product 3 and at δ 169.0, 181.0 for product 4. The resonance of the
N C N carbon atom (C2) of 3 at δ 159.0 was similar to the chemical shift of the
corresponding carbon atom of compound 1a. The signals at δ 163.2, 164.1, 165.2, and
166.4 are due to the four benzoyl carbonyl carbon atoms and the signals at δ 22.0–31.0 are
assigned to tetrahydro benzo carbon atoms. The five signals at δ 86.2, 80.8, 77.3, 75.5, and
63.7 were assigned to C-1ꢁ, C-2ꢁ, C-3ꢁ, C-4ꢁ, and C-5ꢁ of the sugar moiety, respectively.
The 1H NMR of 5 and 6 showed the expected base moiety protons in addition to the
sugar moiety protons (see the Experimental section).
The IR spectrum of compound 3 did not show the signal of a thione group but showed
signals at 1670 cm−1 for the C O group. Stretching vibration frequencies of the benzoyl
carbonyl groups appeared at 1740 cm−1
.
IR spectra of compounds 5 and 6 showed absorptions around 3400 cm−1 for (OH).
Furthermore, the potassium salt of the starting material 2-thioxo-5,6,7,8-
tetrahydrobenzothieno[2,3-d]pyrimidin-4(3H)-one (8) was treated with 2,3,4,6-tetracetyl-
O-acetyl-α-D-glucopyranosyl bromide (9) in dry acetone to give the corresponding
S-glycoside 10 (Scheme 2). Thin layer chromatography showed the formation of a single
unique compound. The structure of the product 10 was established and confirmed by
1
elemental analyses and spectral data (IR, H NMR, 13C NMR) (see the Experimental

NEW S-NUCLEOSIDE DERIVATIVES
1617
O
N
O
N H
S
N H
NaOCH3
S
S
N
S
BzO
O
HO
O
OBz
BzO
BzO
OH
HO
5
3
OAc
OBz
BzO
O
7
2a, X= O, R1 = Si(CH3)3, R2 = H
X
X
HMDS
N-H
N R2
S
S
1
N
H
S
S
2
N
R1
a, X= O
b, X= S
OAc
BzO
O
2b, X= S, R1 = R2 = Si(CH3)3
OBz
BzO
7
OBz
OBz
S
OH
OH
S
N
O
N
O
NaOCH3
S
OBz
S
N
S
N
S
OH
HO
BzO
O
6
O
HO
OH
BzO
OBz
4
Scheme 1
section). The 1H NMR spectrum of 2-(2ꢁ,3ꢁ,4ꢁ,6ꢁ-tetra-O-acetyl-β-D-gluco-pyranosylthio)-
5,6,7,8-tetrahydro-benzothieno[2,3-d]pyrimidin-4-one 10 showed the anomeric proton
ꢁ
ꢁ
of the glucose moiety as a doublet at δ 5.98 with a coupling constant (J1 ,2 ) = 5.1 Hz,
indicating β-configuration of the anomeric center. The other protons of the glucopyranose
ring resonated at δ 3.90–5.50, while the four acetoxy groups appeared as four singlets at δ
2.10–2.20. The 13C NMR revealed the absence of a thione carbon atom at about δ 173.0.
The signals at δ 168.0, 169.0, 169.5, and 170.3 are due to the four acetoxy carbonyl carbon
atoms, and the signals at δ 21.0–22.0 are assigned to the acetate methyl carbon atoms.
The five signals at δ 62.0, 68.0, 69.0, 74.1, and 82.5 were assigned to C-6ꢁ, C-4ꢁ, C-2ꢁ,
C-3ꢁ, and C-5ꢁ, respectively. The IR spectrum of compound 10 did not show the signal of a
thione group, but showed signals at 1675 cm−1 for the C O group. Stretching vibration
frequencies of the acetate carbonyl groups appeared at 1745 cm−1
.

1618
L. M. BREAK ET AL.
O
N-H
O
N
AcO
H
O
OAc
S
N
H
S
N-H
CH3COCH3
+
AcO
-
+
rt
S K
S
O
OAc
Br
OAc
OAc
8
9
OAc OAc
10
CH3ONa
rt
O
N-H
S
N
H
S
HO
O
OH
OH OH
11
Scheme 2
Deacetylation of the blocked nucleoside 10 was achieved in methanolic sodium
methoxide to afford the corresponding deprotected S-nucleoside 11 (Scheme 2). IR spectra
1
of the latter compound showed absorption around 3420 cm−1 for (OH). The H NMR of
11 showed the expected base moiety protons in addition to the sugar moiety protons (see
the Experimental section).
A distinction between the O-, N-, and S-glycosides was possible by comparison of
the 1H NMR and 13C NMR spectra with those of literature data of similar compounds.25–30
13C S Chemical shifts of δ 172.0 were reported for cycloalkyl[4,5]thieno[2,3-d]pyrimidin-
4-one-2-thione, while 2-alkylthio-cycloalkyl[4,5]thieno[2,3-d]pyrimidin-4-one showed
chemical shifts of C-2 around δ 159 ppm. Some literature data of N- and S-glycosides are
shown in Chart 1.
EXPERIMENTAL
Melting points were determined on an Electrothermal apparatus. IR spectra were
recorded in potassium bromide using a PU 9712 spectrophotometer. Elemental analyses
were carried out at the Microanalytical Laboratory in the National Research Center, Giza,
Egypt. 1H and 13C NMR spectra were recorded in the appropriate deuterated solvents using
a Jeol 400 MHz apparatus with tetramethylsilane as an internal standard. IR spectra were
recorded for KBr discs on Testscan Shimadzu FTIR 8000 Series and Bruker IFS 113V
spectrophotometers. 2-Thioxo-5,6,7,8-tetrahydrobenzo-thieno[2,3-d]pyrimidin-4(3H)-one
1a and 2,4-dithioxo-5,6,7,8-tetrahydrobenzo-thieno[2,3-d]pyrimidine 1b were prepared
according to the procedures reported in the literature.19

NEW S-NUCLEOSIDE DERIVATIVES
1619
160.9
O
191.3
187.6
O
O
N
S
S
CH2Ph
CH2Ph
CH2Ph
HN
HN
HN
HN
HN
S
N
H
S
N
H
CH2Ph CH3S
S
N
H
O
N
H
175.9
148.6
172.7
174.7
163.2
[Ref.25]
[Ref.25]
[Ref.25]
[Ref.27]
[Ref.27]
O
N
O
O
N
O
NH
NH
NH
NH
S
S
N
SMe
SCH3
S
S
S
N
S
172.9
168.6
172.4
161.2
[Ref.26]
[Ref.26]
[Ref.29]
[Ref.29]
159.5
NH
O
N
159.0
O
N
H
N
S
S
S
S
OAc
OAc
O
O
OAc
OAc
OAc
OAc
OAc
OAc
[Ref. 30]
product 10
Chart 1
Preparation of 2-(2ꢀ,3ꢀ,5ꢀ-Tri-O-benzoyl-β-D-ribofuranosylthio)-5,6,7,8-
tetrahydrobenzo-thieno[2,3-d]pyrimidin-4(3H)-one (3) and 2,4-Di(2ꢀ,3ꢀ,5ꢀ-
tri-O-benzoyl-β-D-ribofuranosylthio)-5,6,7,8-tetrahydrobenzo-thieno
[2,3-d]pyrimidine (4)
A mixture of 1a or 1b (20 mmol) and dry hexamethyldisilazane (100 mL) was heated
under reflux for 4 h with a catalytic amount of ammonium sulfate (100 mg). After the clear
solution was cooled, it was evaporated to dryness under anhydrous condition to give the
silylated derivative 2a or 2b, respectively, which was directly dissolved in 50 mL of dry
1,2-dichloroethane. To this, a solution of 1-O-acetyl-2,3,5-tri-O-benzoyl-β -D-ribofuranose
(7) (9.6 g, 19.6 mmol) in dry 1,2-dichloroethane (50 mL) was then added. The mixture
was cooled in an ice bath, and a solution of trimethylsilyl trifluoromethanesulfonate (4 mL,
20 mmol) in dry 1,2-dichloroethane (20 mL) was added dropwise. It was stirred at room
temperature for 24 h, and then diluted with chloroform (500 mL), washed with a saturated
solution of aqueous sodium bicarbonate (200 mL) and water (3 × 150 mL), and dried over
anhydrous sodium sulfate. The solvent was removed in vacuo, and the residue was washed
with petroleum ether 60–80 to afford a white solid, which was crystallized from ethanol to
yield colorless crystals of the corresponding nucleoside derivative 3 or 4.
Compound 3. Yield (60%); mp 100–102◦C (ethanol); ν (cm−1) (KBr) 1740, 1670
(CO); 1H NMR (CDCl3): δ 1.30 (m, 2H, CH2), 2.03 (m, 4H, 2CH2), 3.03 (s, 2H, CH2),
H
4.40 (m,1H, H-5ꢁ), 4.73 (d, 1H, H-4ꢁ, J4 ,3 = 4.3 Hz), 4.70 (d, 1H, H-3 , J3 ,4 = 4.4 Hz), 6.09
ꢁ
ꢁ
ꢁ
ꢁ
ꢁ
(t, 1H, H-2ꢁ, J = 5.9 Hz), 6.50 (d, 1H, H-1ꢁ, J1 ,2 = 5.5 Hz), 7.30–8.09 (m, 15H, Ar-H), 11.7
ꢁ
ꢁ

1620
L. M. BREAK ET AL.
(s, 1H, NH); 13C NMR (CDCl3): δ C 22.0, 22.9, 25.0, 31.0 (4 C’s of tetrahydrobenzo), 63.7,
75.5, 77.3, 80.8, 86.2, (sugar carbons), 120.0, 122.0, 125.0, 128.2., 128.5, 129.0, 131.0,
132.0, 133.0, 150.0 (Ar. C’s and 4 C’s of thiophene), 159.0 (N C), 163.2, 164.1, 165.2,
166.4 (4 CO); Anal. Found/ Calcd.: C, 63.50; H, 4.60; N, 4.12; S, 9.40%; C36H30N2O8S2
(682.78); C, 63.33; H, 4.43; N, 4.10; S, 9.39%.
Compound 4. Yield (55%); mp 109–112◦C (EtOH); ν (cm−1) (KBr) 1740 (CO);
1H NMR (CDCl3): δ 1.90 (m, 2H, CH2), 2.40 (m, 4H, 2CH2), 3.30 (s, 2H, CH2), 4.30
H
(m,1H, H-5ꢁ), 4.40 (m,1H, H-5ꢁꢁ), 4.50 (d, 1H, H-4ꢁ, J4 ,3 = 4.3 Hz), 4.70 (d, 1H, H-4ꢁꢁ,
ꢁ
ꢁ
J4 ,3 = 4.3 Hz), 4.85 (d, 1H, H-3ꢁ, J3 ,4 = 4.4 Hz), 4.90 (d, 1H, H-3ꢁꢁ, J3 ,4 = 4.4 Hz), 5.80
ꢁ
ꢁ
ꢁ
ꢁ
ꢁꢁ
ꢁ
(t, 1H, H-2ꢁ, J = 5.8 Hz)), 5.90 (t, 1H, H-2ꢁꢁ, J = 5.8 Hz)), 6.30 (d, 1H, H-1ꢁ, J1 ,2 = 5.5
ꢁ
ꢁ
Hz), 6.40 (d, 1H, H-1ꢁꢁ, J1 ,2 = 5.5 Hz), 7.50–8.04 (m, 30H, Ar-H); 13C NMR (CDCl3): δ
C 22, 22.9, 25, 31 (4 C’s of tetrahydrobenzo), 63.8, 63.9, 71.4, 71.9, 75.3, 75.9, 80.0, 84.0,
84.5, 93.0 (sugar carbons), 129.0, 129.5, 129.8, 130, 131, 132, 133, 134, 150 (Ar. C’s and 4
C’s of thiophene), 158, 159 (N C),164,165,169 (3 CO); Anal. Found/Calcd.: C, 65.00; H,
4.50; N, 2.12; S, 8.50%; C62H50N2O14S3 (1143.29); C, 65.14; H, 4.41; N, 2.45; S, 8.41%.
ꢁ
ꢁ
Preparation of 2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-Tetra-O-acetyl-β-D-glucopyranosyl
thio)-5,6,7,8-tetrahydrobenzo-thieno[2,3-d]pyrimidin-4(3H)-one (10)
To a solution of 1a (5 mmol) in aqueous potassium hydroxide [(0.28 g, 5 mmol) in
distilled H2O (4 mL)], a solution of 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl bromide 9
(2.06 g, 5 mmol) in acetone (20 mL) was added. The reaction mixture was stirred at room
temperature overnight (12 h) and judged to be complete by TLC (CHCl3/MeOH, 9:1).
The solvent was evaporated under reduced pressure at 40◦C, and the crude product was
filtered off and washed with distilled H2O (3 × 4 mL) to remove the potassium bromide
that formed. The product was dried and crystallized from the proper solvent to afford the
desired product 10.
Compound 10. Pale white powder, yield (70%), mp 180–182◦C (ethanol); IR
1
(KBr) ν cm−1: 1745, 1675, 1520; H NMR (DMSO): δH 1.80 (m, 2H, CH2), 2.10–2.20
(4s, 12H, 4CH3), 2.35(m, 4H, 2CH2), 3.21(t, 2H, CH2, J = 7.1 Hz), 3.90 (m, 1H, H-5ꢁ),
4.00–4.25 (d, 2H, H-6ꢁ, J = 5.1 Hz), 5.20 (t, 1H, H-3ꢁ, J = 5.0 Hz), 5.50 (t, 1H, H-2ꢁ, J =
5.0 Hz), 5.98 (d, 1H, H-1ꢁ, J1 ,2 = 5.1 Hz), 11.5 (s, 1H, NH); 13C NMR (DMSO): δC 21.0,
21.5, 21.7, 22.0, 27.0, 27.5, 27.7, 29.0, 30.0, 33.0, 62.0, 68.0, 69.0, 74.1, 82.5, 120.0, 136.4,
137.0, 152.0, 158.5, 159.8, 168.0, 169.0, 169.5, 170.3; Anal. Found/Calcd.: C, 51.00; H,
4.90; N, 4.70; S, 11.50%; C24H28N2O10S2 (568.63); C, 50.70; H, 4.96; N, 4.93; S, 11.28%.
ꢁ
ꢁ
Deprotection of 3, 4, and 10: Synthesis of 2-(β-D-Ribofuranosylthio)-
5,6,7,8-tetrahydrobenzo-thieno[2,3-d]pyrimidin-4(3H)-one (5),
2,4-Di(β-D-ribofuranosylthio)-5,6,7,8-tetrahydrobenzo-thieno[2,3-d]-
pyrimidine (6), and 2-(2ꢀ,3ꢀ,4ꢀ,6ꢀ-Tetrahydroxy-β-D-glucopyranosylthio)-
5,6,7,8-tetrahydrobenzo-thieno[2,3-d]pyrimidin-4(3H)-one (11)
A mixture each of the protected nucleosides 3, 4, and 10 (2 mmol), absolute methanol
(40 mL), and sodium methoxide (120 mg, 2.2 mol) was stirred at room temperature for 24
h. Evaporation of the solvent under vacuum gave a colorless solid, which was dissolved in
hot water and neutralized with acetic acid. The precipitate was filtered off and afforded,

NEW S-NUCLEOSIDE DERIVATIVES
1621
upon crystallization from water, the free nucleosides 5, 6, and 11, respectively as colorless
crystals.
Compound 5. Yield (45%); mp 177–179◦C (H2O), ν (cm−1) (KBr) 3400 (OH);
1H NMR (DMSO-d6): δH 1.80 (m, 2H, CH2), 2.80 (m, 4H, 2CH2), 3.30 (s, 2H, CH2),
3.70–3.85(m, 2H, H-5ꢁ), 4.00 (m, 1H, H-4ꢁ), 4.20 (m, 1H, H-3ꢁ), 4.35–4.40 (m, 1H, H-2ꢁ),
4.7–4.8 (t, 1H, OH-5ꢁ, J = 5.8 Hz), 5.1–5.2 (d, 1H, OH-3ꢁ, J = 5.8 Hz), 5.4–5.5 (d, 1H,
OH-2ꢁ, J = 5.5 Hz), 6.1–6.2 (d, 1H, J1 ,2 = 5.5 Hz, H-1ꢁ), 11.7 (s, 1H, NH); 13C NMR
(DMSO-d6): δC 22.0, 22.7, 24.1, 25.0 (4 C’s of tetrahydrobenzo), 61.7, 70.8, 75.8, 85.3,
87.8, (sugar carbons), 128.0, 129.0, 130.0, 132.0 (4 C’s of thiophene), 158.0 (N C) 165.0
(CO); Anal. Found/ Calcd.: C, 48.50; H, 4.60; N, 7.42; S, 17.40%; C15H18N2O5S2 (370.45);
C, 48.63; H,4 .90; N, 7.56; S, 17.31%.
ꢁ
ꢁ
Compound 6. Yield (40%); mp 203–204◦C (H2O/EtOH, 1:1); ν (cm−1) (KBr)
1
3400 (OH); H NMR (DMSO-d6): δH 2.00 (m, 2H, CH2), 2.40 (m, 4H, 2CH2), 3.30 (s,
2H, CH2), 3.85 (m, 2H, H-5ꢁ), 3.95 (m,1H, H-5ꢁꢁ), 4.10 (m, 1H, H-4ꢁ), 4.20 (d, 1H, H-4ꢁꢁ,
J = 5.5 Hz), 4.30 (m, 1H, H-3ꢁ), 4.35 (d, 1H, H-3ꢁꢁ, J = 5.5 Hz), 4.40 (m, 1H, H-2ꢁ), 4.50
(m, 1H, H-2ꢁꢁ), 4.7 (t, 1H, OH-5ꢁ, J = 6.8 Hz), 5.1 (d, 1H, OH-3ꢁ, J = 5.5 Hz), 5.30 (d,
1H, OH-2ꢁ, J = 5.5 Hz), 6.00 (d,1H, J1 ,2 = 5.5 Hz, H-1ꢁ), 6.10 (d, 1H, H-1ꢁꢁ, J1 ,2 = 5.4
ꢁ
ꢁ
ꢁ
ꢁ
Hz); 13C NMR (CDCl3): δ 22.0, 23.0, 25.0, 31.0 (4 C’s of tetrahydrobenzo), 61.4, 64.6,
C
71.5, 72.6, 75.5, 75.9, 80.0, 83.0, 93.0, 94.8 (sugar carbons), 128.0, 129.0, 130.0, 131.0 (4
C’s of thiophene), 158.0, 159.0 (N C); Anal. Found/Calcd.: C, 46.10; H, 5.20; N, 5.42; S,
18.50%; C20H26N2O8S3 (518.63); C, 46.32; H, 5.05; N, 5.40; S, 18.55%.
Compound 11. White powder, yield (40%), mp 222–223◦C (ethanol; IR (KBr) ν
1
cm−1: 3420 (OH); H NMR (DMSO-d6): δH 1.10 (t, 2H, OH-2ꢁ + OH-3ꢁ, J = 5.0 Hz),
1.40(m, 2H, OH-4ꢁ + OH-5ꢁ), 1.90 (m, 2H, CH2), 2.20 (m, 4H, 2CH2), 3.12 (t, 2H, CH2,
J = 6.9 Hz), 3.45 (s, 1H, H-2ꢁ), 3.90 (s, 2H, H-3ꢁ + H-4ꢁ), 4.20 (d, 3H, H-5ꢁ + H-6ꢁ, J = 5.2
Hz), 6.50 (t, 1H, H-1ꢁ, J1 ,2 = 5.0), 11.2 (s, 1H, NH); Anal. Found/Calcd.: C, 47.99; H, 5.03;
ꢁ
ꢁ
N, 7.00; S, 16.01%; C16H20N2O6S2 (400.48); C, 47.80; H, 5.25; N, 6.94; S, 15.97%%.
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