Synthesis of novel guanidinogalactosides

Article abstract of DOI:10.1002/jccs.200900057

This paper involves the preparation of thioureas, which couple with per-O-acetylated galactosyl isothiocyanate 1 and 2-aminobenzothiazole 2 to give incorporating galactosylthiourea derivatives 3. Nucleophilic addition of active primary amine to 3 in the p

Full text of DOI:10.1002/jccs.200900057

392
Journal of the Chinese Chemical Society, 2009, 56, 392-397
Synthesis of Novel Guanidinogalactosides
Jin-Feng Yang (
College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi, Xinjiang 830046, P. R. China
) and Ling-Hua Cao* (
)
This paper involves the preparation of thioureas, which couple with per-O-acetylated galactosyl iso-
thiocyanate 1 and 2-aminobenzothiazole 2 to give incorporating galactosylthiourea derivatives 3. Nu-
cleophilic addition of active primary amine to 3 in the presence of HgCl2 afforded the per-O-acetylated
guanidinogalactoside 4a-4d, 5a-5d, 6a-6d, 7a-7d in good yield. These adducts were subjected to deace-
tylation in MeOH/NaOMe and furnished the corresponding unprotected guanidinogalactosides 8a-8d,
9a-9d, 10a-10d, 11a-11d. The structures of all newly synthesized compounds were established by IR, 1H
NMR, MS and elemental analysis.
Keywords: Galactosyl isothiocyanate; Benzothiazole; Guanidinogalactoside.
INTRODUCTION
Guanidines are structurally novel molecules reported
guanidine-containing sugars have attracted the attention of
the pharmaceutical industry.8 D-galactose is a normal re-
ducing sugar in the body.9 Glycoside analogs of b-galac-
tosylceramide are a novel class of small molecule antiviral
agents that inhibit HIV-1 entry.10 In recent years, galactose
has become of considerable importance as a pharmaco-
phoric group, which has been synthesized by many meth-
ods.11,12 However, guanidine-like molecules which contain
galactosyl have not been reported.
to exhibit remarkable biological and pharmacological ac-
tivities, which are affected by the guanidine functionality.1
The guanidine moiety has been incorporated into many
drugs covering a variety of therapeutic areas.2 A number of
benzothiazolyl guanidines have been synthesized and re-
ported to exhibit antibacterial and antitubercular activity.3
Guanidino-containing sugar and sugar-like molecules also
have a wide range of biologically important uses such as in-
hibition of replication of HIV,4 antihypertensives,5 antibac-
terial activity,6 and inhibition of nitric oxide syntheses.7 So,
In recent years, many efficient methods of preparing
guanidine have been demonstrated. However, some of
these methods showed limited success on account of unde-
Scheme I
* Corresponding author. E-mail: clhxj@xju.edu.cn

Synthesis of Novel Guanidinogalactosides
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 393
sirable conditions and unstable starting materials, espe-
cially in the synthesis of guanidine containing sugars,13 and
these reactions were considered to go via a carbodiimide
intermediates. In contrast, we have synthesized a series of
new guanidinogalactoside in one step and did not isolate
carbodiimide intermediates in the work. The results indi-
cated that the electron-donating groups on the benzene ring
were favorable to the addition reaction. The resultant
amine can be either alkyl or aryl.
in the carbohydrate field, sugar isothiocyanates play a
pivotal role in the preparation of a broad spectrum of car-
bohydrate derivatives, mostly having a thiourea structure,
for biological and pharmaceutical interests.16,17 In order to
broaden the synthesis and activities research of glycosyl-
guanidine, we obtained a series of new guanidinogalacto-
sides. HIV PR inhibitory and anti-inflluenza activity of
these compounds have been evaluated, some of which did
not display obvious biological activity.
Isothiocyanates are vesertile synthetic intermediates
in organic chemistry due to their availability and their ten-
dency to undergo nucleophilic additions.14,15 Particularly
RESULTS AND DISCUSSION
We used per-O-acetylated galactosyl isothiocyanate
Table 1. Physical data, the elemental analysis and MS data of new compounds
Elemental analysis (calcd) %
Compd.
Formula
Yield% m.p./°C
MS m/z (%)
C
H
N
3a
C22H25N3O9S2
C23H27N3O9S2
C23H27N3O9S2
C23H27N3O10S2
C25H32N4O9S
C25H32N4O9S
C28H29N4O9SCl
C29H32N4O10S
C26H34N4O9S
C26H34N4O9S
C29H31N4O9SCl
C30H34N4O10S
C26H34N4O9S
C26H34N4O9S
C29H31N4O9SCl
C30H34N4O10S
C26H34N4O10S
C26H34N4O10S
C29H31N4O10SCl
C30H34N4O11S
C17H24N4O5S
C17H24N4O5S
C20H21N4O5SCl
C21H24N4O6S
C18H26N4O5S
C18H26N4O5S
C21H23N4O5SCl
C22H26N4O6S
C18H26N4O5S
C18H26N4O5S
C21H23N4O5SCl
C22H26N4O6S
C18H26N4O6S
C18H26N4O6S
C21H23N4O6SCl
C22H26N4O7S
80
82
85
84
85
82
75
78
82
76
72
80
81
85
70
71
79
78
72
73
89
80
81
79
81
85
80
81
79
81
79
76
80
82
78
80
211-212 49.03 (48.97)
4.65 (4.67)
4.90 (4.92)
4.91 (4.92)
4.76 (4.78)
5.70 (5.72)
5.69 (5.72)
4.64 (4.62)
5.15 (5.13)
5.92 (5.93)
5.91 (5.93)
4.82 (4.84)
5.36 (5.34)
5.91 (5.93)
5.94 (5.93)
4.82 (4.84)
5.33 (5.34)
5.78 (5.77)
5.75 (5.77)
4.73 (4.72)
5.19 (5.21)
7.76 (7.79) 540 ([M+H]+, 100)
7.57 (7.59) 554 ([M+H]+, 100)
7.56 (7.59) 554 ([M+H]+, 100)
7.41 (7.38) 570 ([M+H]+, 100)
3b
3c
219-220 49.95 (49.90)
198-199 49.84 (49.90)
188-189 48.45 (48.50)
154-155 53.11 (53.17)
149-150 53.22 (53.17)
191-193 53.08 (53.15)
118-120 55.46 (55.40)
174-175 53.91 (53.96)
148-150 54.01 (53.96)
178-179 53.79 (53.86)
198-199 56.00 (56.06)
158-159 53.99 (53.96)
163-165 53.91 (53.96)
183-185 53.91 (53.86)
182-183 56.01 (56.06)
3d
4a
9.96 (9.93)
9.91 (9.93)
8.83 (8.86)
8.90 (8.92)
9.71 (9.69)
9.66 (9.69)
8.68 (8.67)
8.75 (8.72)
9.71 (9.69)
9.67 (9.69)
8.64 (8.67)
8.75 (8.72)
9.41 (9.43)
9.45 (9.43)
8.49 (8.46)
8.52 (8.51)
563 ([M–H]–, 100)
563 ([M–H]–, 100)
632 ([M–H]–, 100)
627 ([M–H]–, 100)
577 ([M–H]–, 100)
577 ([M–H]–, 100)
646 ([M–H]–, 100)
641 ([M–H]–, 100)
577 ([M–H]–, 100)
577 ([M–H]–, 100)
646 ([M–H]–, 100)
641 ([M–H]–, 100)
593 ([M–H]–, 100)
593 ([M–H]–, 100)
662 ([M–H]–, 100)
657 ([M–H]–, 100)
4b
4c
4d
5a
5b
5c
5d
6a
6b
6c
6d
7a
98-99
52.57 (52.51)
7b
7c
144-146 52.48 (52.51)
198-199 52.49 (52.56)
184-186 54.75 (54.70)
123-125 51.57 (51.50)
129-130 51.45 (51.50)
145-146 51.65 (51.71)
188-190 54.73 (54.77)
123-124 52.71 (52.66)
120-122 52.62 (52.66)
142-144 52.76 (52.71)
208-210 55.76 (55.68)
116-118 52.62 (52.66)
123-125 52.73 (52.66)
154-156 52.76 (52.71)
140-142 55.74 (55.68)
137-138 50.62 (50.69)
112-114 50.73 (50.69)
150-152 50.94 (51.00)
206-207 53.81 (53.86)
7d
8a
6.09 (6.11) 14.10 (14.14) 395 ([M–H]–, 100)
6.12 (6.11) 14.17 (14.14) 395 ([M–H]–, 100)
4.55 (4.56) 12.09 (12.07) 464 ([M–H]–, 100)
5.23 (5.26) 12.15 (12.17) 459 ([M–H]–, 100)
6.37 (6.39) 13.64 (13.66) 409 ([M–H]–, 100)
6.40 (6.39) 13.68 (13.66) 409 ([M–H]–, 100)
4.83 (4.85) 11.75 (11.72) 478 ([M–H]–, 100)
5.50 (5.53) 11.78 (11.81) 473 ([M–H]–, 100)
6.41 (6.39) 13.62 (13.66) 409 ([M–H]–, 100)
6.37 (6.39) 13.63 (13.66) 409 ([M–H]–, 100)
4.83 (4.85) 11.74 (11.72) 478 ([M–H]–, 100)
5.50 (5.53) 11.83 (11.81) 473 ([M–H]–, 100)
6.14 (6.15) 13.17 (13.14) 425 ([M–H]–, 100)
6.17 (6.15) 13.12 (13.14) 425 ([M–H]–, 100)
4.68 (4.69) 11.39 (11.34) 494 ([M–H]–, 100)
5.35 (5.35) 11.47 (11.43) 489 ([M–H]–, 100)
8b
8c
8d
9a
9b
9c
9d
10a
10b
10c
10d
11a
11b
11c
11d

394 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Yang and Cao
Table 2. IR spectral data for new compounds
Compd.
IR (KBr) n/cm-1
3a
3376 (m, NH), 1757 (s, C=O), 1512 (m, N-C=S), 1216 (s, C–O–C), 911 (m, C1–H)
3347 (m, NH), 1747 (s, C=O), 1515 (m, N-C=S), 1217 (s, C–O–C), 913 (m, C1–H)
3334 (m, NH), 1750 (s, C=O), 1518 (m, N-C=S), 1218 (s, C–O–C), 914 (m, C1–H)
3356 (m, NH), 1749 (s, C=O), 1517 (m, N-C=S), 1221 (s, C–O–C), 913 (m, C1–H)
3b
3c
3d
4a
3434 (s, NH), 3371 (s, NH), 1747 (s, C=O), 1616 (s, guanidino), 1216 (s, C–O–C), 908 (m, sugar ring C1–H)
3421 (m, NH), 1757 (s, C=O), 1618 (s, guanidino), 1220 (s, C–O–C), 910 (m, sugar ring C1–H)
3446 (m, NH), 1748 (s, C=O), 1614 (s, guanidino), 1216 (s, C–O–C), 913 (m, sugar ring C1–H)
3447 (m, NH), 1754 (s, C=O), 1616 (s, guanidino), 1222 (s, C–O–C), 915 (m, sugar ring C1–H)
3427 (m, NH), 3390 (s, NH), 1748 (s, C=O), 1617 (s, guanidino), 1223 (s, C–O–C), 910 (m, sugar ring C1–H)
3440 (m, NH), 1749 (s, C=O), 1617 (s, guanidino), 1217 (s, C–O–C), 916 (m, sugar ring C1–H)
3438 (m, NH), 1748 (s, C=O), 1620 (s, guanidino), 1224 (s, C–O–C), 917 (m, sugar ring C1–H)
3445 (m, NH), 1753 (s, C=O), 1616 (s, guanidino), 1232 (s, C–O–C), 913 (m, sugar ring C1–H)
3430 (m, NH), 3363 (s, NH), 1758 (s, C=O), 1612 (s, guanidino), 1221 (s, C–O–C), 910 (m, sugar ring C1–H)
3456 (m, NH), 1750 (s, C=O), 1616 (s, guanidino), 1221 (s, C–O–C), 914 (m, sugar ring C1–H)
3446 (m, NH), 1748 (s, C=O), 1620 (s, guanidino), 1229 (s, C–O–C), 913 (m, sugar ring C1–H)
3451 (m, NH), 1751 (s, C=O), 1612 (s, guanidino), 1219 (s, C–O–C), 913 (m, sugar ring C1–H)
3444 (m, NH), 3380 (m, NH), 1751 (s, C=O), 1615 (s, guanidino), 1216 (s, C–O–C), 910 (m, sugar ring C1–H)
3472 (m, NH), 1756 (s, C=O), 1615 (s, guanidino), 1216 (s, C–O–C), 906 (m, sugar ring C1–H)
3453 (m, NH), 1748 (s, C=O), 1621 (s, guanidino), 1216 (s, C–O–C), 913 (m, sugar ring C1–H)
3429 (m, NH), 1746 (s, C=O), 1606 (s, guanidino), 1216 (s, C–O–C), 910 (m, sugar ring C1-H)
3523 (s, NH), 3346 (s, OH), 1613 (s, guanidino), 1215 (s, C–O–C), 913 (m, sugar ring C1–H)
3527 (s, NH), 3347 (m, OH), 1608 (s, guanidino), 1218 (s, C–O–C), 918 (m, sugar ring C1–H)
3532 (s, NH), 3328 (m, OH), 1616 (s, guanidino), 1209 (s, C–O–C), 913 (m, sugar ring C1–H)
3527 (s, NH), 3331 (m, OH), 1612 (s, guanidino), 1218 (s, C–O–C), 913 (m, sugar ring C1–H)
3538 (s, NH), 3349 (m, OH), 1609 (s, guanidino), 1210 (s, C-O-C), 914 (m, sugar ring C1–H)
3567 (s, NH), 3358 (m, OH), 1607 (s, guanidino), 1211 (s, C–O–C), 910 (m, sugar ring C1–H)
3543 (s, NH), 3328 (m, OH), 1608 (s, guanidino), 1218 (s, C–O–C), 915 (m, sugar ring C1–H)
3537 (s, NH), 3336 (m, OH), 1612 (s, guanidino), 1210 (s, C–O–C), 913 (m, sugar ring C1–H)
3549 (s, NH), 3356 (m, OH), 1611 (s, guanidino), 1209 (s, C–O–C), 911 (m, sugar ring C1–H)
3563 (s, NH), 3355 (m, OH), 1613 (s, guanidino), 1216 (s, C–O–C), 913 (m, sugar ring C1–H)
3546 (s, NH), 3361 (m, OH), 1606 (s, guanidino l), 1220 (s, C–O–C), 913 (m, sugar ring C1–H)
3569 (s, NH), 3546 (m, OH), 1608 (s, guanidino ), 1218 (s, C–O–C), 913 (m, sugar ring C1–H)
3563 (s, NH), 3353 (m, OH), 1606 (s, guanidino), 1210 (s, C–O–C), 910 (m, sugar ring C1–H)
3476 (s, NH), 3343 (m, OH), 1611 (s, guanidino), 1208 (s, C–O–C), 908 (m, sugar ring C1–H)
3555 (s, NH), 3364 (m, OH), 1618 (s, guanidino l), 1216 (s, C–O–C), 913 (m, sugar ring C1–H)
3567 (s, NH), 3362 (m, OH), 1614 (s, guanidino), 1213 (s, C–O–C), 917 (m, sugar ring C1–H)
4b
4c
4d
5a
5b
5c
5d
6a
6b
6c
6d
7a
7b
7c
7d
8a
8b
8c
8d
9a
9b
9c
9d
10a
10b
10c
10d
11a
11b
11c
11d
as the starting material, which reacted with 2-aminobenzo-
thiazole derivatives in dry benzene to give galactosylthio-
ureas 3a-3d. Treatment of 3a-3d with various active amines,
and using HgCl2 as a regent for desulfurization, a series of
new guanidinoglycoside compounds 4a-4d, 5a-5d, 6a-6d,
7a-7d have been obtained. These compounds were further
deacetylated in MeOH/NaOMe to generate the correspond-
ing deacetylated guanidinogalactosides 8a-8d, 9a-9d, 10a-
10d, 11a-11d.
thioureido at about 1500 cm-1, the compounds 4-11 were
characterized by a strong band at about 1610 cm-1, assigned
to guanidine. And then there were no bands of thioureido at
about 1500 cm-1. The band at 913 cm-1 indicated that all
new compounds were in common 4C1 (b-nomer).
In the 1H NMR spectra of compounds 4a-4d, 5a-5d,
6a-6d and 7a-7d, the proton signal of the acetyl group in
the glycosyl ring appeared at about d 2.00-2.65 and showed
the four independent absorption peaks in the event of the
chemical environmental difference. The resonance peaks
of the d 3.80-5.40 were assigned to sugar ring protons. It is
the signal of sugar ring C1–H that appeared at d 5.50 which
shifted to the low-field displacement and presented triplet
In the IR spectra, all new compounds 4-7 showed
peaks in the region of 3500-3200 cm-1 (N–H stretching),
1750 cm-1 (C=O stretching) and 1240-1210 cm-1 (C–O–C).
In contrast with compounds 3a-3d, which showed bands of

Synthesis of Novel Guanidinogalactosides
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 395
Table 3. 1H NMR spectral data of new compounds
Compd.
1H NMR (CDCl3, 400 MHZ), d
3a
3b
3c
3d
4a
4b
1.98, 2.02, 2.06, 2.18 (4s, 12H, 4 ´ COCH3), 3.9 -5.34 (m, 6H, sugar ring 2,3,4,5,6–H), 5.45 (t, J = 9.6 Hz, 1H, sugar ring
C1–H), 7.03-7.46 (m, 4H, ArH), 10.11-10.33 (br, 1H, NH), 11.44-11.77 (s, 1H, NH)
1.52 (s, 3H, CH3), 1.98, 2.04, 2.16, 2.50 (4s, 12H, 4 ´ COCH3), 3.95-5.25 (m, 6H, sugar ring 2,3,4,5,6–H), 5.45 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 7.03-7.48 (m, 3H, ArH), 10.11-10.33 (br, 1H, NH), 11.39-11.72 (br, 1H, NH)
1.43 (s, 3H, CH3), 2.00, 2.08, 2.18, 2.42 (4s, 12H, 4 ´ COCH3), 4.10-5.24 (m, 6H, sugar ring 2,3,4,5,6–H), 5.44 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 7.14-7.60 (m, 3H, ArH), 10.11-10.33 (br, 1H, NH), 11.46-11.71 (br, 1H, NH)
2.00, 2.04, 2.20, 2.42 (4s, 12H, 4 ´ COCH3), 3.78 (s, 3H, OCH3), 3.95-5.18 (m, 6H, sugar ring 2,3,4,5,6–H), 5.42 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 7.13-7.62 (m, 3H, ArH), 10.11-10.33 (br, 1H, NH), 11.36-11.70 (br, 1H, NH)
1.23-1.34 (d, J = 7.2 Hz, 6H, 2 ´ CH3), 1.98, 2.02, 2.05, 2.18 (4s, 12H, 4 ´ COCH3), 3.66 (s, 1H, NH), 3.95-5.32 (m, 7H,
sugar ring 2,3,4,5,6–H, CH), 5.49 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.03-7.46 (m, 4H, ArH), 10.09 (s, 1H, NH)
1.01 (t, J = 6.0 Hz, 3H, CH3), 1.64 (m, 2H, CH2), 1.98, 2.00, 2.04, 2.18 (4s, 12H, 4 ´ COCH3), 3.14 (m, 2H, CH2), 3.89-
5.22 (m, 6H, sugar ring 2,3,4,5,6–H), 5.39 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 5.62 (s, 1H, NH), 7.03-7.48 (m, 4H, ArH),
10.29 (s, 1H, NH)
4c
4d
5a
1.98, 2.02, 2.07, 2.19 (4s, 12H, 4 ´ COCH3), 4.08-5.40 (m, 6H, sugar ring 2,3,4,5,6–H), 5.58 (t, J = 9.6 Hz, 1H, sugar ring
C1–H), 7.09-7.58 (m, 7H, ArH), 10.11 (d, 1H, NH), 12.12 (d, 1H, NH)
1.98, 2.02, 2.06, 2.19 (4s, 12H, 4 ´ COCH3), 3.80 (s, 3H, OCH3), 3.95-5.26 (m, 6H, sugar ring 2,3,4,5,6–H), 5.46 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 7.06-7.46 (m, 7H, ArH), 10.12 (d, J = 9.2 Hz, 1H, NH), 12.05 (s, 1H, NH)
1.23-1.36 (d, J = 7.2 Hz, 6H, 2 ´ CH3), 1.52 (s, 3H, CH3), 2.02, 2.04, 2.18, 2.54 (4s, 12H, 4 ´ COCH3), 3.62 (s, 1H, NH),
4.05-5.25 (m, 7H, sugar ring 2,3,4,5,6–H, CH), 5.48 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.03-7.48 (m, 3H, ArH), 10.52 (s,
1H, NH)
5b
1.01 (t, J = 6.0 Hz, 3H, CH3), 1.51 (s, 3H, CH3), 1.64 (m, 2H, CH2), 2.00, 2.05, 2.17, 2.51 (4s, 12H, 4 ´ COCH3), 3.14 (m,
2H, CH2), 3.95-5.21 (m, 7H, sugar ring 2,3,4,5,6–H, NH), 5.48 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.05-7.48 (m, 3H,
ArH), 10.49 (s, 1H, NH)
5c
5d
6a
1.54 (s, 3H, CH3), 2.00, 2.04, 2.24, 2.52 (4s, 12H, 4 ´ COCH3), 4.12-5.40 (m, 6H, sugar ring 2,3,4,5,6–H), 5.63 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 7.09-7.58 (m, 7H, ArH), 10.21 (d, 1H, NH), 12.33 (s, 1H, NH)
1.53 (s, 3H, CH3), 2.00, 2.06, 2.18, 2.50 (4s, 12H, 4 ´ COCH3), 3.78 (s, 3H, OCH3), 3.89-5.26 (m, 6H, sugar ring 2,3,4,5,6–
H), 5.41 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.06-7.57 (m, 7H, ArH), 10.02 (d, J = 9.2 Hz, 1H, NH), 12.03 (s, 1H, NH)
1.25-1.34 (d, J = 7.0 Hz, 6H, 2 ´ CH3), 1.42 (s, 3H, CH3), 2.00, 2.18, 2.20, 2.39 (4s, 12H, 4×COCH3), 3.70 (s, 1H, NH),
4.10-5.25 (m, 7H, sugar ring 2,3,4,5,6–H, CH), 5.48 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.15-59 (m, 3H, ArH), 10.52 (s,
1H, NH)
6b
1.04 (t, J = 6.0 Hz, 3H, CH3), 1.43 (s, 3H, CH3), 1.60 (m, 2H, CH2), 2.00, 2.08, 2.19, 2.40 (4s, 12H, 4 ´ COCH3), 3.14 (m,
3H, CH2), 4.10-5.22 (m, 7H, sugar ring 2,3,4,5,6–H, NH), 5.45 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.14-7.64 (m, 3H,
ArH), 10.49 (s, 1H, NH)
6c
6d
7a
1.42 (s, 3H, CH3), 2.00, 2.08, 2.17, 2.41 (4s, 12H, 4 ´ COCH3), 4.06-5.22 (m, 6H, sugar ring 2,3,4,5,6–H), 5.43 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 7.09-7.58 (m, 7H, ArH), 10.11 (d, 1H, NH), 12.26 (s, 1H, NH)
1.41 (s, 3H, CH3), 1.98, 2.08, 2.18, 2.44 (4s, 12H, 4 ´ COCH3), 3.78 (s, 3H, OCH3), 3.89-5.24 (m, 6H, sugar ring 2,3,4,5,6–
H), 5.41 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.06-7.57 (m, 7H, ArH), 10.12 (d, J = 9.2 Hz, 1H, NH), 12.06 (s, 1H, NH)
1.26-1.38 (d, J = 7.2 Hz, 6H, 2 ´ CH3), 2.00, 2.04, 2.18, 2.44 (4s, 12H, 4 ´ COCH3), 3.69 (s, 1H, NH), 3.80 (s, 3H, OCH3),
3.98-5.13 (m, 7H, sugar ring 2,3,4,5,6–H, CH), 5.28 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 7.22-7.68 (m, 3H, ArH), 10.76 (s,
1H, NH)
7b
1.03 (t, J = 6.0 Hz, 3H, CH3), 1.58 (m, 3H, CH2), 2.00, 2.04, 2.20, 2.42 (4s, 12H, 4 ´ COCH3), 3.12 (m, 2H, CH2), 3.73 (s,
3H, OCH3), 3.95-5.08 (m, 6H, sugar ring 2,3,4,5,6–H), 5.22 (t, J = 9.6 Hz, 1H, sugar ring C1-H), 5.37 (s, 1H, NH), 7.13-
7.69 (m, 3H, ArH), 10.67 (s, 1H, NH)
7c
7d
8a
8b
2.00, 2.10, 2.18, 2.42 (4s, 12H, 4 ´ COCH3), 3.78 (s, 3H, OCH3), 3.95-5.20 (m, 6H, sugar ring-H 2,3,4,5,6–H), 5.42 (t, J =
9.6 Hz, 1H, sugar ring C1–H), 7.11-7.52 (m, 7H, ArH), 10.09 (d, J = 9.2 Hz, 1H, NH), 12.24 (s, 1H, NH)
2.00, 2.06, 2.17, 2.45 (4s, 12H, 4 ´ COCH3), 3.79 (s, 6H, 2 ´ OCH3), 3.95-5.20 (m, 6H, sugar ring 2,3,4,5,6–H), 5.42 (t, J =
9.6 Hz, 1H, sugar ring C1–H), 7.06-7.56 (m, 7H, ArH), 10.12 (d, J = 9.2 Hz, 1H, NH), 12.16 (s, 1H, NH);
1.23-1.34 (d, J = 7.2 Hz, 6H, 2 ´ CH3), 3.23-3.67 (m, 7H, sugar ring 2,3,4,5,6–H, NH), 4.34 (t, J = 9.4 Hz, 1H, sugar ring
C1–H), 4.23-5.64 (m, 5H, sugar ring–OH, CH), 7.04-7.48 (m, 4H, ArH), 9.72 (d, J = 9.2 Hz, 1H, NH)
1.01 (t, J = 6.0 Hz, 3H, CH3), 1.64 (m, 2H, CH2), 3.14 (m, 2H, CH2), 3.23-3.64 (m, 6H, sugar ring 2,3,4,5,6–H), 4.34 (t, J =
9.4 Hz, 1H, sugar ring C1–H), 4.23-5.65 (m, 5H, sugar ring–OH, NH), 7.03-7.48 (m, 4H, ArH), 9.69 (d, J = 9.2 Hz, 1H,
NH)

396 J. Chin. Chem. Soc., Vol. 56, No. 2, 2009
Yang and Cao
8c
8d
9a
9b
3.34-3.64 (m, 6H, sugar ring 2,3,4,5,6–H,), 4.34 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.22 (m, 4H, sugar ring–OH),
7.09-7.56 (m, 7H, ArH), 10.11 (d, J = 9.2 Hz, 1H, NH), 12.12 (s, 1H, NH)
3.34-3.64 (m, 6H, sugar ring 2,3,4,5,6–H,), 3.81 (s, 3H, OCH3), 4.32 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.22 (m, 4H,
sugar ring–OH), 7.06-7.48 (m, 7H, ArH), 10.08 (d, J = 8.8 Hz, 1H, NH), 12.05 (s, 1H, NH)
1.24-1.36 (d, J = 7.2 Hz, 6H, 2 ´ CH3), 2.52 (s, 3H, CH3), 3.34-3.64 (m, 7H, sugar ring 2,3,4,5,6–H, NH), 4.34 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 4.58-5.22 (m, 5H, sugar ring–OH, CH), 7.03-7.48 (m, 3H, ArH), 10.43 (d, J = 8.8 Hz, 1H, NH)
1.01 (t, J = 6.0 Hz, 3H, CH3), 2.51 (s, 3H, CH3), 1.64 (m, 2H, CH2), 3.14 (m, 2H, CH2), 3.34-3.64 (m, 6H, sugar ring
2,3,4,5,6–H), 4.34 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.40-5.22 (m, 5H, sugar ring–OH, NH), 7.05-7.48 (m, 3H, ArH),
10.12 (d, J = 8.8 Hz, 1H, NH)
9c
2.51 (s, 3H, CH3), 3.34-3.68 (m, 6H, sugar ring 2,3,4,5,6–H), 4.34 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.22 (m, 4H,
sugar ring–OH), 7.09-7.58 (m, 7H, ArH), 9.66 (d, J = 8.8 Hz, 1H, NH), 12.21 (s, 1H, NH)
9d
2.51 (s, 3H, CH3), 3.30-3.80 (m, 9H, sugar ring 2,3,4,5,6–H, OCH3), 4.32 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.21
(m, 4H, sugar ring–OH), 7.06-7.56 (m, 7H, ArH), 9.64 (d, J = 9.2 Hz, 1H, NH), 12.03 (s, 1H, NH)
1.25-1.34 (d, J = 7.0 Hz, 6H, 2 ´ CH3), 1.48 (s, 3H, CH3), 3.34-3.72 (m, 7H, sugar ring 2,3,4,5,6–H, NH), 4.34 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 4.58-5.25 (m, 5H, sugar ring–OH, CH), 7.15-7.59 (m, 3H, ArH), 9.68 (d, J = 8.8 Hz, 1H, NH)
1.04 (t, J = 7.0 Hz, 3H, CH3), 1.48 (s, 3H, CH3), 1.60 (m, 2H, CH2), 3.14 (m, 3H, CH2), 3.32-3.69 (m, 6H, sugar ring
2,3,4,5,6–H), 4.34 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.64 (m, 5H, sugar ring–OH, NH), 7.12-7.61 (m, 3H, ArH),
9.59 (d, J = 8.8 Hz, 1H, NH)
10a
10b
10c
10d
11a
11b
1.42 (s, 3H, CH3), 3.32-3.64 (m, 6H, sugar ring 2,3,4,5,6–H), 4.34 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.23 (m, 4H,
sugar ring–OH), 7.06-7.54 (m, 7H, ArH), 9.64 (d, J = 8.8 Hz, 1H, NH), 12.02 (s, 1H, NH)
1.41 (s, 3H, CH3), 3.32-3.86 (m, 9H, sugar ring 2,3,4,5,6–H, OCH3), 4.34 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.23
(m, 4H, sugar ring–OH), 7.06-7.57 (m, 7H, ArH), 9.58 (d, J = 9.2 Hz, 1H, NH), 12.06 (s, 1H, NH)
1.26-1.34 (d, J = 7.2 Hz, 6H, 2 ´ CH3), 3.32-3.71 (m, 7H, sugar ring 2,3,4,5,6–H, NH), 3.78 (s, 3H, OCH3), 4.34 (t, J = 9.6
Hz, 1H, sugar ring C1–H), 4.58-5.23 (m, 4H, sugar ring–OH), 7.17-7.64 (m, 3H, ArH), 9.67 (d, J = 9.2 Hz, 1H, NH)
1.03 (t, J = 7.0 Hz, 3H, CH3), 1.58 (m, 3H, CH2), 3.12 (m, 2H, CH2), 3.32-3.64 (m, 6H, sugar ring 2,3,4,5,6–H), 3.80 (s, 3H,
OCH3), 4.32 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.37 (m, 5H, sugar ring–OH, NH), 7.18-7.65 (m, 3H, ArH), 9.72 (d,
J = 8.8 Hz, 1H, NH)
11c
3.32-3.65 (m, 6H, sugar ring 2,3,4,5,6-H), 3.81 (s, 3H, OCH3), 4.35 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.58-5.23 (m, 4H,
sugar ring–OH), 7.11-7.54 (m, 7H, ArH), 9.66 (d, J = 8.8 Hz, 1H, NH), 12.04 (s, 1H, NH)
11d
3.34-3.64 (m, 6H, sugar ring 2,3,4,5,6–H), 3.79 (s, 6H, 2 ´ OCH3), 4.34 (t, J = 9.6 Hz, 1H, sugar ring C1–H), 4.55-5.25 (m,
4H, sugar ring–OH), 7.06-7.56 (m, 7H, ArH), 9.62 (d, J = 8.8 Hz, 1H, NH), 12.02 (s, 1H, NH)
peaks due to the deshielding of O, N. The data J = 8-10 Hz
further indicated the b-anomer. In the 1H NMR spectra of
compounds 8a-8d, 9a-9d, 10a-10d and 11a-11d, N–H con-
nected with sugar ring C1–H appearing at about d 9.76 and
split into two peaks due to the impact of coupling. The pro-
ton signal of the glycosyl ring showed multiple peaks at
about d 3.23-3.64. It is worth noting that O–H showed a
chemical shift in the range of d 4.58-5.30 and that it is easy
to identify because of its short and lively peak shape of the
features. It was confirmed that such absorption by D2O ex-
changing was disappearing.
scopic melting point apparatus. The IR spectra were re-
corded in KBr pellets on a Bruker Equinox-55 FT-IR appa-
ratus. The 1H NMR spectra were recorded on an INOVA-
400 (using TMS as internal standard, DMSO-d6 or CDCl3
as solvent). Mass spectra were recorded on an HP 1100
LC-MS (ESI). Elemental analyses were performed on a
Thermo Flash EA-1112 analyzer. All reagents were com-
mercial products of analytical grade and can be used di-
rectly without purification except where especially noted.
1. Compound 1 was prepared according to the re-
ported method18
The MS (ESI) spectra displayed that all the com-
pounds had quasi-molecular peaks, most of which were the
base peaks. This type of compound is stable.
Yield 55%, m.p. 92-93 °C (lit18: m.p. 92-94 °C).
2. Compounds 2a-2d were prepared according to the
reported method19
2a: Yield 85%, m.p. 130-132 °C (lit19: 131-132 °C);
2b: Yield 65%, m.p. 126-128 °C (lit19: 128-130 °C);
2c: Yield 65%, m.p. 134-136 °C (lit19: 135-136 °C);
2d: Yield 72%, m.p. 161-162 °C (lit19: 160-162 °C).
EXPERIMENT
General method
Melting points were taken on a Yanaco MP-S3 micro-

Synthesis of Novel Guanidinogalactosides
J. Chin. Chem. Soc., Vol. 56, No. 2, 2009 397
3. General procedure for the preparation of galac-
tosyl thiourea derivatives (3a-3d)
the National Natural Science Foundation of China (No.
20462006) and Xinjiang Key Laboratory of Plant Re-
sources & Natural Products Chemistry. We are grateful to
the National Center of China for Drug Screening for the
anti-ACE and HIV PR inhibitory test.
An equimolecular mixture of galactosyl isothiocya-
nates 1 and the 2-amino-4/6-benzothizole 2a-2d in 15 mL
dry benzene was refluxed (TLC, 1:1 EtOAc-petroleum
ether) for 12 h, then concentrated in vacuo. The residue was
crystallized from ethanol to give compounds as colorless
crystals in good yield.
Received September 26, 2008.
4. General procedure for the preparation of N-Alkyl-
N¢-(4/6-substituted benzothiazol-2-yl)-N²-(2,3,4,6-
tetra-O-acetyl-b-D-guanidinogalactosides (4a-4d,
5a-5d, 6a-6d, 7a-7d)
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ACKNOWLEDGEMENT
This work was supported by the financial support of