Concise stereoselective synthesis of 5-hydroxy carba-β-D-rhamnose, carba-β-D-rhamnose, (-)-gabosine O, and carba-α-D-rhamnose

Article abstract of DOI:10.1080/07328303.2016.1170138

A divergent approach was developed for the synthesis of 5-hydroxy carba-β-D-rhamnose 1, carba-β-D-rhamnose 2, (-)-gabosine O 3, and carba-α-D-rhamnose 4 starting from D-ribose using ring closing metathesis (RCM).

Full text of DOI:10.1080/07328303.2016.1170138

Journal of Carbohydrate Chemistry
ISSN: 0732-8303 (Print) 1532-2327 (Online) Journal homepage: http://www.tandfonline.com/loi/lcar20
Concise stereoselective synthesis of 5-hydroxy
carba-β-D-rhamnose, carba-β-D-rhamnose, (-)-
gabosine O, and carba-α-D-rhamnose
Gurrapu Raju, Maddimsetti Venkateswara Rao & Batchu Venkateswara Rao
To cite this article: Gurrapu Raju, Maddimsetti Venkateswara Rao & Batchu Venkateswara
Rao (2016) Concise stereoselective synthesis of 5-hydroxy carba-β-D-rhamnose, carba-β-D-
rhamnose, (-)-gabosine O, and carba-α-D-rhamnose, Journal of Carbohydrate Chemistry, 35:3,
150-160, DOI: 10.1080/07328303.2016.1170138
To link to this article: http://dx.doi.org/10.1080/07328303.2016.1170138
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Date: 07 June 2016, At: 08:43

JOURNAL OF CARBOHYDRATE CHEMISTRY
, VOL. , NO. , –
http://dx.doi.org/./..
Concise stereoselective synthesis of -hydroxy
carba-β-D-rhamnose, carba-β-D-rhamnose, (-)-gabosine O,
and carba-α-D-rhamnose
Gurrapu Raju, Maddimsetti Venkateswara Rao, and Batchu Venkateswara Rao
Organic and Biomolecular Chemistry Division, CSIR-Indian Institute of Chemical Technology, Hyderabad,
Telangana, India.
ABSTRACT
ARTICLE HISTORY
Received  December 
Accepted  March 
A divergent approach was developed for the synthesis of
5-hydroxy carba-β-D-rhamnose 1, carba-β-D-rhamnose 2, (-)-
gabosine O 3, and carba-α-D-rhamnose 4 starting from D-ribose
using ring closing metathesis (RCM).
KEYWORDS
BH-Reduction; Grignard
addition; Oxidation; RCM;
Silyl protection
GRAPHICAL ABSTRACT
Introduction
Carbasugars, a family of carbohydrate mimics, have attracted great interest due
to their interesting biological properties. The ability of carbasugars to mimic the
natural sugars in size, structure, and polarity and also their stability towards hydrol-
ysis make them potential candidates as inhibitors of glycosidases and glycosyl-
transferases, etc. The development of synthetic strategies towards carbasugars from
carbohydrates as precursors has advantage over other commonly used approaches,
as the final product can be obtained with high optical purity and the stereochemistry
can be maintained throughout the synthetic sequence.
In 1974, gabosines (Fig. 1), a class of carbasugars, were isolated from Strep-
tomyces strains. A total of 14 different gabosines have been identified and the
absolute configuration of gabosine A–F, I, L, N, and O has been established.[1,2]
The intense interest in these natural products is encouraged by their interesting
CONTACT Gurrapu Raju
rajugurrapu@gmail.com
Organic and Biomolecular Chemistry Division, CSIR-Indian
Institute of Chemical Technology, Hyderabad, Telangana , India.
Supplementary material for this article can be accessed on the publisher’s website.
©  Taylor & Francis Group, LLC

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151
Figure . Structures of Mycobacterium tuberculosis cell-wall, gabosines, and carbarhamnoses.
biological properties such as antibiotic, anticancer, and DNA binding properties.
Furthermore, gabosines can be considered as chemical precursors of 6-deoxy-
carba pyranose derivatives which are known for the inhibition of oligosaccharide
processing enzymes.[3] Carbarhamnoses are potential inhibitor of rhamnosyl-
transferases which are responsible for cell growth of Mycobacterium tuberculosis[4]
and ultimately become a non-toxic treatment for TB.[5] Furthermore, carbarham-
noses were used in the preparation of stable trisaccharides which were present in
synthetic vaccines for Streptococcus pneumoniae infections.[6] Because of the inter-
esting structures and biological properties of carbarhamnoses and gabosines, a few
syntheses for gabosines and carbarhamnoses have been reported in literature.[7,8]
In the past few years, our group has been involved in developing new strategies
for the synthesis of carbasugars from carbohydrates.[9,10] In continuation, herein
we are reporting a short, efficient, and common strategy (Sch. 1) for the synthesis of
5-hydroxy carba-β-D-rhamnose 1, carba-β-D-rhamnose 2, (-)-gabosine O 3, and
carba-α-D-rhamnose 4 RCM. The key aspect of our synthesis is the efficient prepa-
ration of a diene precursor 6 for RCM. Since, we believe that the success of RCM
strategy depends on how one can make efficiently the diene precursor.
Results and discussion
Retro synthetic analysis (Sch. 1) indicated that compound 5 can be obtained from
RCM of diene 6, which in turn can be derived from D-ribose 7 by simple trans-
formations. Compound 7 was subjected to acetonide protection followed by one

152
G. RAJU ET AL.
Scheme . Retro synthetic analysis of the synthetic targets.
carbon homologation using Wittig reaction to give diol 9 using reported procedure
(Sch. 2).[11] Treatment of diol 9 with sodiummetaperiodate in dichloromethane gave
aldehyde, which was directly used for Grignard reaction with β-methallyl mag-
nesium chloride[12] in ether at 0°C to yield diene 6 in 3:1 ratio as an insepara-
ble diastereomeric mixture, with anti-isomer as the major product. The formation
of anti-isomer as the major product can be explained by non-chelated Felkin–Anh
model.
The diastereomeric mixture of diene mixture 6 was subjected to RCM using
Grubbs second generation catalyst in dichloromethane under reflux condition [13]
to afford the separable cyclohexetols 10 and 11 in 3:1 ratio. We have chosen the
major isomer 10 as a common intermediate for the synthesis of 5-hydroxy-carba-
β-D-rhamnose 1, carba-β-D-rhamnose 2, and (-)-gabosine O 3.
Dihydroxylation of compound 10 with OsO4 in THF and H2O (2:1) gave com-
pound 12 whose spectral data is good in agreement with the reported data.[7g]
Deprotection of the acetonide to give 5-hydroxyl carba-β-D-rhamnose 1 was
Scheme. (i) acetone, HSO (cat), rt,  h, %. (ii) PhPCHBr, KOtBu, THF, °C,  h, %. (iii) (a) NaIO,
CHCl, HO, °C,  h; (b) β-methallyl magnesium chloride, ether, °C, overnight, %. (iv) Grubbs
second generation catalyst, CHCl, reflux,  h, %.

JOURNAL OF CARBOHYDRATE CHEMISTRY
153
Scheme . (i) OsO, NMO, THF and HO (:), °C to rt,  h, %. (ii) TESCl, imdizole, CHCl, °C to
rt,  min, %. (iii) BH.DMS, THF, °C to rt,  h, %. (iv)  N HCl, MeOH, rt,  h, %. (v) Dess Martin
periodinane, CHCl, °C to rt,  h, %. (vi) Amberlyst -, THF, HO, reflux,  h, %.
®
already in the reported literature.[7g] Homo allylic alcohol in compound 10 was con-
verted to silyl ether by treating with TESCl and imidazole in dichloromethane to
afford compound 13 in a 95% yield. Then compound 13 was subjected to hydrob-
oration with BH3.DMS to afford compound 14 as an exclusive product. Global
deprotection of compound 14 with 3 N HCl smoothly gave carba-β-D-rhamnose
2 (Sch. 3).
To prepare (-)-gabosine O 3, the secondary alcohol in compound 14 was sub-
jected to oxidation with Dess Martin periodinane in dichloromethane to produce
the keto compound 15. Then, deprotection of the acetonide and silyl groups in 15
was carried out with Amberlyst -15 to furnish the gabosine O 3 in a 92% yield
®
(Sch. 3). The spectral and analytical data of 5-hydroxy carba-β-D-rhamnose 12,
carba-β-D-rhamnose 2, and (-)-gabosine O 3 are in good agreement with reported
values.[7f–g]
We also utilized the minor isomer 11 to prepare carba-α-D-rhamnose 4 (Sch. 4).
For this purpose, the homo allylic alcohol in compound 11 was converted into silyl
ether by reacting with TESCl in dichloromethane to give compound 16. Compound
16 was subjected to hydroboration followed by deprotection with 3 N HCl to afford
Scheme . (i) TESCl, imdizole, CHCl, °C to rt,  min, %. (ii) BH.DMS, THF, °C to rt,  h, %. (iii)
 N HCl, MeOH, rt,  h, %.

154
G. RAJU ET AL.
Table . Glycosidase inhibitory activities of compounds 2 and 3.
IC value (in µM)
Enzymes
carba-β-D-rhamnose 2
carba-α-D-rhamnose 4
α-galactosidase
β-galactosidaes
α-glucosidase
β-glucosidase
.
NI
.
NI
NI
NI
NI
NI
NI = No Inhibition observed up to  µM.
carba-α-D-rhamnose 4. Spectral data of compound 4 was in good agreement with
the reported values.[7c]
Finally, carba-β-D-rhamnose 2 and carba-α-D-rhamnose 4 were biologically
evaluated as potential inhibitors of α-galactosidase, β-galactosidase, α-glucosidase,
and β-glucosidase. As shown in Table 1, compound 2 was found to have moderate
inhibition on α-glucosidase and α-galactosidase with IC50 values of 0.152 µM and
0.231µM, respectively, whereas no inhibition on β-glucosidase and β-galactosidase.
On the other hand, compound 4 did not show inhibition of on all four enzymes at
up to 50 µM concentration.
Conclusion
In summary, stereoselective and divergent syntheses of 5-hydroxy carba-β-D-
rhamnose 1, carba-β-D-rhamnose 2, (-)- gabosine O 3, and carba-α-D-rhamnose
4 were accomplished in good overall yields. This strategy is also useful to prepare
some other carbasugar analogues. Studies on the glycosidase inhibitory activity of
carba-β-D-rhamnose 2 and carba-α-D-rhamnose 4 revealed that 2 had moderate
activities to inhibit α-glucosidase and α-galactosidase with IC50 values of 0.152 µM
and 0.231 µM, respectively.
Experimental
General methods: Moisture and oxygen sensitive reactions were carried out under
N2 atmosphere in flame or oven dried glassware with magnetic stirring. Solvents
were distilled under standard procedures, and THF used was freshly distilled over
Na and benzophenone. All reactions were monitored by TLC (silica-coated plates,
visualized under UV light or by phosphomolibdidate solution staining). Before con-
centration of the solvent, the organic layer was dried over Na2SO4. Column chro-
matography (CC) was performed on silica gel (60–120 mesh) using mixtures of
AcOEt and hexane as eluents. Melting points (mp) were determined on a Fisher
John’s melting point apparatus and were uncorrected. IR spectra were recorded on
a Perkin–Elmer RX-1 FT-IR system. 1H NMR and 13C NMR spectra were recorded
1
using Varian Gemini-200, Bruker Avance-300, and Inova-500 spectrometers. H
NMR data are expressed as chemical shifts in ppm followed by multiplicity, num-
ber of proton(s), and coupling constant(s) quoted in J (Hz). 13C NMR chemical

JOURNAL OF CARBOHYDRATE CHEMISTRY
155
shifts are expressed in ppm. Optical rotations were measured with a JASCO digi-
tal polarimeter. High resolution MS was performed on a Q STAR mass spectrom-
eter. α-Glucosidase from Saccharomyces cerevisiae (cat. # G5003), β-glucosidase
from almond (cat. # 49290), α-galactosidase from green coffee beans (cat. # G8507),
β-galactosidase from Kluyveromyces lactis (cat. # G3665), 4-nitrophenyl β-D-
glucopyranoside (cat. # N7006), and 4-Nitrophenyl α-D-glucopyranoside (cat #
N1377) used in biological assays were purchased from commercial sources.
1-((4R,5S)-2, 2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-3-methylbut-3-en-1-ol
(6). To a stirred solution of diol 9 (6.7 g, 35.6 mmol) in dichloromethane (60 mL)
was added drop wise an aqueous solution of NaIO4 (11.4 g, 53.4 mmol, 1.5 M
solution) at 0°C and the reaction mixture was stirred at rt for 40 min. After water
(50 mL) was added, the mixture was extracted with methylene chloride (600 mL),
dried, filtered, and evaporated under reduced pressure. The crude product was
directly treated with solution of β-methallyl magnesium chloride prepared from
Mg (7.69 g, 320.5 mmol) and β-methyallyl chloride (25.2 mL, 256.4 mmol) in
ether (60 mL) at 0°C. After stirring for overnight at rt, the reaction mixture was
poured into saturated aqueous NH4Cl (150 mL) and extracted with ethyl acetate
(3 × 150 mL). The combined organic layers were washed with water, brine, and
dried over Na2SO4, concentrated under reduced pressure and purified through
CC (hexane/ethyl acetate 4:1) to afford the corresponding diastereomeric mixture
(3:1) diene 6 as a colorless oil (6.6 g, 80%). [α]30 = –2.16 (c = 1.6, CHCl3); IR
D
(neat): 3462, 2923, 2876, 2854, 1792, 1729, 1459, 1380, 1237, 1117, 741 cm−1; 1H
NMR (CDCl3, 500 MHz): δ 6.09–5.96 (m, 1H), 5.42, 5.36∗ (d, J = 17.7, J∗ = 17.1,
1H), 5.26–5.32 (dd, J = 10.2, 9.1, 1H), 4.90, 4.85∗ (s, s∗, 1H), 4.82, 4.79∗ (s, s∗, 1H),
4.71–4.65, 4.60–4.55∗ (dd, J = 6.8, J∗ = 7.4, 1H), 4.07–4.02∗, 4.0–3.94 (dd, J∗ = 7.4,
6.2, J = 7.4, 6.8, 1H), 3.76 (m, 1H), 2.5 (d, J = 13.7, 1H), 2.21–2.09 (m, 2H), 1.78,
1.75∗ (s, s∗, 3H), 1.53∗, 1.49 (s∗, s, 3H), 1.40∗, 1.38 (s∗, s, 3H,); 13C NMR (CDCl3,
75 MHz,): δ 142.2, 141.9∗, 134.3, 134.0∗, 119.5∗, 117.9, 113.7, 113.2∗, 108.6, 108.6,
80.5, 80.1∗, 79.1∗, 78.8, 67.6∗, 67.1∗, 42.4, 42.1∗, 27.7, 27.3∗, 25.3, 25.0∗, 22.4; ESIMS:
m/z 235 [M+Na]+; HRMS: calcd for C12H20O3Na [M+Na]+ = 235.1304, found
235.1303. ∗ indicates isomer peaks.
(3aR,4R,7aS)-2,2,6-Trimethyl-3a,4,5,7a-tetrahydrobenzo[d] [1,3]dioxol-4-ol.
(10) & (3aR,4S,7aS)-2,2,6-Trimethyl-3a,4,5,7a-tetrahydrobenzo[d][1,3]dioxol-
4-ol (11). To the diene 6 (4.5 g, 21.2 mmol) in dry CH2Cl2 (840 mL), Grubbs II
generation catalyst (0.89 g, 1.06 mmol) was added and the resulting purple solution
was turned to brown after 10 min. The reaction mixture was refluxed for 8 h, con-
centrated under reduced pressure, and the residue was purified by CC (hexane/ethyl
acetate: 7:3) to give compound 10 (2.5 g, 64%) & 11 (0.89 g, 22%) as light brown oils
(3.39 g, 87%).
Data for compound 10: [α]30 = +2.5 (c = 0.5, CHCl3); IR(neat): 3414, 2983,
D
1
2922, 1671, 1438, 1377, 1229, 1163, 1104, 1024, 853 cm−1; H NMR (CDCl3,
600 MHz): δ 5.58 (bs, 1H), 4.59 (bs, 1H), 3.94–3.91 (dd, J = 6.4, 8.6, 1H), 3.83 (m,
1H), 2.29–2.22 (dd, J = 5.2, 16.9, 1H), 2.09–2.02 (dd, J = 10.1, 16.9, 1H), 1.78 (s,
3H), 1.49 (s, 3H), 1.40 (s, 3H); 13C NMR (CDCl3, 75MHz): δ 138.6, 118.0, 109,

156
G. RAJU ET AL.
79.1, 73.1, 69.4, 35.8, 28.4, 25.9, 23.4; ESIMS: m/z 207 [M+Na]+; HRMS: calcd for
C10H16O3Na = 207.09917 [M+Na]+, found 207.0994.
Data for compound 11: [α]30 = +1.5 (c = 0.8, CHCl3); IR(neat): 3437, 2983,
D
2923, 2854, 1441, 1377, 1214, 1054, 893 cm−1; 1H NMR (CDCl3, 300 MHz): δ 5.46
(bs, 1H), 4.60 (bs, 1H), 4.35–4.27 (dd, J = 3.0, 6.0, 1H), 3.89 (m, 1H), 2.35–2.22 (dd,
J = 7.1, 16.9, 1H), 2.18–2.07 (dd, J = 4.1, 16.9, 1H), 1.75 (s, 3H), 1.42 (s, 3H), 1.39 (s,
3H); 13C NMR (CDCl3, 75 MHz): δ 135.4, 119.6, 109.1, 75.1, 73.4, 67.18, 33.9, 27.2,
26.0, 23.5; ESIMS: m/z 207 [M+Na]+; HRMS; calcd for C10H16O3Na = 207.09917
[M+Na]+, found 207.0994.
(3aS,4S,5R,7R,7aR)-2,2,5-Trimethyl hexahydrobenzo [d][1,3]dioxole-4,5,7-
triol (12). To a stirred soln. of the compound 10 (0.1 g, 0.5 mmol) in THF/ H2O (2:1,
mL) were added NMO monohydrate (0.12 g, 1 mmol) followed by OsO4 (0.002 g,
0.01 mmol) at 0°C and stirred at rt for 24 h. After addition of Na2SO3 the reac-
tion mixture was diluted with H2O and extracted with CH2Cl2 (3 × 5 mL). The
combined organic layers were dried over anhydrous Na2SO4, concentrated under
reduced pressure, purified by CC (hexane/AcOEt: 2:8) to give compound 12 as col-
20
orless oil (0.1 g, 85%). [α]30 = –48.5 (c = 1.5, CHCl3) {lit.[7g] [α]
= –49.6
D
D
(c = 0.82, CHCl3)}; IR (neat): 3392, 2988, 2884, 1644, 1375, 1215 cm−1. 1H NMR
(DMSO-d6, 300 MHz,): δ 4.98 (d, J = 6.6, 1H), 4.86 (d, J = 6.6, 1H), 4.56 (s, 1H),
4.05 (dd, J = 6.6, 1H), 3.98 (dd, J = 6.0, 1H,), 3.69 (m, 1H), 3.26 (dd, J = 6.6, 1H,),
1.67–1.61 (m, 2H), 1.40 (s, 3H), 1.28 (s, 3H), 1.14 (s, 3H); 13C NMR (DMSO-d6,
75 MHz): δ 107.4, 79.3, 78.2, 74.1, 71.7, 67.3, 40.5, 27.9, 26.3, 25.6; ESIMS: m/z 241
[M+Na]+; HRMS: calcd for C10H18O5 = 241.10435 [M+Na]+, found 241.10464
Triethyl((3aS,4R,7aS)-2,2,6-Trimethyl-3a,4,5,7a-tetrahydro
benzo[d][1,3]dioxol-4-yloxy)silane (13). To an ice cooled stirred soln. of alcohol
10 (2 g, 10.8 mmol) in dry CH2Cl2 (20 mL) was added imidazole (1.47 g, 21.7mmol)
and TESCl (2.49 mL, 16.3 mmol) and stirred for 20 min. The reaction mixture
was extracted in CH2Cl2 (50 mL) and washed with brine. The organic layer was
separated, dried over anhydrous Na2SO4, concentrated, and purified by CC using
hexane/ethyl acetate (19:1) to give 13 (2.8 g, 95%) as a colors oil [α]30 = +6.2
D
(c = 1.8, CHCl3); IR (neat): 2954, 2912, 2876, 1457, 1378, 1212, 1103, 1058,
741 cm−1; 1H NMR (CDCl3, 500 MHz): δ 5.53 (bs, 1H), 4.59 (bs, 1H), 3.93 (m, 1H),
3.83 (m, 1H), 2.17–2.11 (dd, J = 5.0, 17.0, 1H), 2.05–1.98 (dd, J = 8.6, 17.0, 1H),
1.74 (s, 3H), 1.46 (s, 3H), 1.38 (s, 3H), 0.97 (9H, J = 7.9 1t), 0.7–0.53 (m, 6H); 13
C
NMR (CDCl3, 75 MHz): δ 137.5, 118.3, 108.5, 78.4, 73.2, 69.8, 37.2, 28.2, 25.9, 23.5,
6.7, 4.8; ESIMS: m/z 321 [M+Na]+; HRMS: calcd for C16H30O3NaSi = 321.1856
[M+Na]+, found 321.1850.
(3aS,4R,5S,7R,7aS)-2,2,5-Trimethyl-7-(triethylsilyloxy)hexahydrobenzo
[d][1,3]dioxol-4-ol (14). To a solution of 13 (2 g, 7.4 mmol) in THF (20 mL),
BH3.Me2S (1.2 mL, 14.8 mmol) was added drop wise at –10°C. Stirring was con-
tinued for 30 min at rt. The reaction mixture was quenched by the addition of 10%
NaOH (3mL) followed by 30% H2O2 (3 mL) at 0°C. The reaction was allowed to
warm to rt and stirred for another 2 h. The reaction mixture was extracted with

JOURNAL OF CARBOHYDRATE CHEMISTRY
157
AcOEt (2 × 50 mL) and the combined organic extracts were washed with brine,
separated, and dried over anhydrous Na2SO4. The solvent was removed on a rotary
evaporator and the residue was purified by CC on silica gel using hexane/AcOEt
(7:3) as the eluant to give pure compound 14 (1.5 g, 70%) as a colorless liquid.
[α]30 = +135 (c = 0.18, CHCl3); IR (neat): 3395, 2953, 2910, 2876,1457, 1414,
D
1
1219, 1044, 723 cm−1; H NMR (CDCl3, 300 MHz): δ 4.21 (t, J = 4.1, 1H), 3.90
(m, 1H), 3.83–3.77 (dd, J = 4.9, 7.5, 1H), 3.34–3.24 (dd, J = 7.5, 10.5, 1H), 2.50 (bs,
1H), 1.65–1.57 (m, 2H), 1.53 (s, 3H), 1.35 (s, 3H), 1.03 (d, J = 6.4, 3H), 0.95 (t, J =
7.9, 9H), 0.7–0.58 (m, 6H); 13C NMR (CDCl3, 75 MHz): δ 109.6, 81.8, 77.9, 77.7,
68.8, 36.2, 32.8, 28.4, 26.1, 17.7, 6.7, 4.6; ESIMS: m/z 317 [M+H]+; HRMS: calcd
for C16H33O4Si = 317.2142 [M+H]+, found 317.2138.
(1R,2R,3S,4R,5S)-5-Methylcyclohexane-1,2,3,4-tetraol (2). Compound 14
(0.5 g, 1.7 mmol) was taken in MeOH (5 mL), to this soln. at rt aq. 3 N HCl (2 mL)
was added. Then the reaction was stirred for 12 h at r.t. After completion of the
reaction, volatiles were removed under vacuum. Purification by silica flash chro-
matography using MeOH/CHCl3 (1:20) as the eluant provided alcohol 2 (0.25 g,
90%) as white solid. Mp: 160–161°; [α]30 = +6.2 (c = 1.0, CH3OH) {lit.[7f] for
D
enantiomer [α]28D = –5.4.0. (c = 0.7, CH3OH)}; IR (neat): 3315, 2923, 1645, 1552,
1412, 1220, 1056, 966, 771 cm−1; 1H NMR (CD3OD, 300 MHz,): δ 3.98 (bs, 1H),
3.65 (m, 1H), 3.26–3.31 (m, 2H), 1.49–1.61 (m, 2H), 1.36 (m, 1H), 1.07 (d, J = 6.8,
3H); 13C NMR (CD3OD, 300 MHz): δ 76.2, 76.1, 75.0, 70.6, 36.2, 35.2, 18.5; ESIMS:
m/z 185 [M+Na]+; HRMS: calcd for C7H14O4Na = 185.07805 [M+Na]+, found
185.07843.
(3aR,5S,7R,7aS)-2,2,5-Trimethyl-7-triethylsilyloxy)tetrahydrobenzo[d][1,3]
dioxol-4(3aH)-one (15). To an ice cold soln. of compound 14 (1 g, 3.4 mmol)
in CH2Cl2 (10 mL), Dess Martin periodane (2.9 g, 6.9 mmol) was added. After
being stirred at 0°C for 1 h, the reaction mixture was diluted with ether (20 mL)
followed by 1:1 sat. NaHCO3 and Na2SO3 solution (5 mL) was added. The reac-
tion mixture was extracted with ether (3 × 20 mL) and the organic layer was
washed with H2O and brine, dried over anhydrous Na2SO4. The solvent was
removed under reduced pressure and the crude was purified through CC (hex-
ane/AcOEt: 7:3) to afford corresponding alcohol 15 (0.8 g, 80%) as a colorless oil.
[α]30 = –220 (c = 0.7, CHCl3); IR (neat): 2923, 2854, 1791, 1729, 1459, 1380,
D
1220, 1117, 772 cm−1; 1H NMR (CDCl3, 500 MHz): δ 4.48 (m, 1H), 4.31–4.26 (m,
2H), 2.36 (m, 1H), 1.99–1.93 (m, 2H), 1.44 (s, 3H), 1.38 (s, 3H), 1.11 (d, J = 6.5,
3H), 0.98 (t, J = 8.0, 9H), 0.66 (q, J = 7.7, 15.7, 6H); 13C NMR (CDCl3, 75 MHz):
δ 208.1, 110.4, 80.0, 78.3, 67.6, 39.3, 36.2, 26.9, 25.7, 14.2, 6.7, 4.7; ESIMS: m/z
316 [M+H]+; HRMS: calcd for C16H31O4Si = 315.1986 [M+H]+, found 315.
1990.
Gabosine O (3). To the solution of compound 15 (0.5 g, 1.7 mmol), in THF
(5 mL) and H2O (1 mL), Amberlyst −15 resin (20 mg) was added and refluxed
®
at 70°C for 5 h. The reaction mixture was filtered and the filtrate was concentrated
under reduced pressure to give syrup which was purified through CC to give gabo-
sine O 3 (0.25 g, 92%) yield as a white solid, mp: 108–109°; [α]30D = –20 (c = 1.0,

158
G. RAJU ET AL.
CH3OH) {lit.[8a] [α]20D = –21.0 (c 0.07, MeOH}; IR (neat): 3434, 3278, 2926, 1718,
1435, 1409, 1219, 1034, 990, 772 cm−1; 1H NMR (CD3OD, 300 MHz): δ 4.25–4.28
(m, 1H), 4.18–4.22 (m, 1H), 4.14–4.18 (m, 1H), 2.46–2.60 (m, 1H), 1.96–2.07 (m,
1H), 1.82 (q, J = 12.3, 1H,), 1.03 (d, J = 6.5, 3H); 13C NMR (CD3OD, 300 MHz): δ
212.1, 78.1, 76.9, 69.4, 39.7, 37.8, 14.0; ESIMS: m/z 183 [M+Na]+, HRMS: calcd for
C7H13O4 = 161.0808 [M + H]+, found 161.0809.
Triethyl (3aS,4S,7aS)-2,2,6-trimethyl-3a,4,5,7a-tetrahydro benzo[d][1,3]dio-
xol-4-yloxy)silane (16). To an ice cooled stirred solution of alcohol 11 (0.8 g,
4.3 mmol) in dry CH2Cl2 (5 mL) was added imidazole (0.59 g, 8.7 mmol) and TESCl
(1.1 mL, 6.5 mmol) and stirred for 20 min. The reaction mixture was extracted in
CH2Cl2 (20 mL) and washed with brine. The organic layer was separated, dried over
anh. Na2SO4, concentrated, and purified by CC using hexane/AcOEt (19:1) to give
16 (1.1 g, 95%) as a colors oil [α]30D = +11 (c = 1.0, CHCl3); IR (neat): 2954, 2912,
2876, 1457, 1378, 1212, 1103, 1058, 741 cm−1; 1H NMR (CDCl3, 500 MHz): δ 5.26
(bs, 1H), 4.56 (bs, 1H), 4.26 (m, 1H), 3.90–3.85 (dd, J = 2.2, 5.3, 10.3, 1H), 2.40
(m, 1H), 1.96–1.90 (dd, J = 5.4, 16.1 1H), 1.70 (s, 3H), 1.37 (s, 6H), 0.97 (t, J = 8,
9H), 0.64 (m, 6H); 13C NMR (CDCl3, 75 MHz): δ 137.5, 118.3, 108.5, 78.4, 73.2, 69.8,
37.2, 28.2, 25.9, 23.5, 6.7, 4.8; ESIMS: m/z 321 [M+Na]+; HRMS: calcd for C16H30O3
NaSi = 321.1856 [M+Na]+, found 321.1850.
(3aS,4R,5S,7S,7aS)-2,2,5-Trimethyl-7-(triethylsilyloxy)hexahydrobenzo
[d][1,3]dioxol-4-ol (17). To a solution of 16 (1 g, 3.7 mmol) in THF (10 mL),
BH3.Me2S (0.57 mL, 7.4 mmol) was added drop wise at –10 °C. Stirring was
continued for 30 min at rt. The reaction mixture was quenched by the addition of
10% NaOH (2 mL) followed by 30% H2O2 (2 mL) at 0°C. The reaction was allowed
to warm to rt and stirred for another 2 h. The reaction mixture was extracted
with AcOEt (2 × 20 mL) and the combined organic extracts were washed with
brine, separated, and dried over anh. Na2SO4. The solvent was removed on a rotary
evaporator and the residue was purified by CC on silica gel using hexane/AcOEt
(7:3) as the eluant to give pure compound 17 (0.74 g, 70%) as a colorless liquid.
[α]30 = –2.8 (c = 1.4, CHCl3); IR (neat): 3395, 2953, 2911, 2877, 1457, 1414,
D
1219 cm−1; 1H NMR (CDCl3, 300 MHz): δ 4.10–4.02 (m, 3H), 3.35–3.25 (dd, J =
6.2, 9.4, 1H), 1.92 (m, 1H), 1.80–1.56 (m, 2H), 1.49 (s, 3H), 1.35 (s, 3H), 1.09–0.88
(m, 2H), 0.65–0.54 (m, 6H); 13C NMR (CDCl3, 75 MHz): δ 108.8, 80.2, 78.8, 77.4,
67.5, 35.8, 29.5, 28.0, 25.9, 18.1, 6.7, 4.6; ESIMS: m/z 317 [M+Na]+; HRMS: calcd
for C16H33O4Si = 317.2142 [M+Na]+, found 317.2138.
(1S,2R,3S,4R,5S)-5-Methylcyclohexane-1,2,3,4-tetraol (4). Compound 17
(0.5 g, 1.7 mmol) was taken in MeOH (5 mL) to this soln. at rt aq. 3 N HCl (2 mL)
was added. The mixture was stirred for 12 h at rt. After completion of the reaction
mixture solvent was removed under vacuum. Purification by silica flash chromatog-
raphy using MeOH&CHCl3 (1:20) as the eluant provided alcohol 4 (0.25 g, 90%) as
a colorless oil. [α]30 = –18.3 (c = 1.5, CH3OH); {lit[7c] [α] 20 = –17.24 (c 0.58,
D
D
1
CH3OH} IR (neat): 3315, 2923, 1412, 1220, 1056, 966 cm−1; H NMR (CD3OD,
300 MHz): δ 3.87 (dd, J = 3.5, 3.0, 1H,), 3.83 (dd, J = 3.5, 3.0, 3.0, 1H), 3.61

JOURNAL OF CARBOHYDRATE CHEMISTRY
159
(dd, J = 9.6, 3.0, 1H) 3.26 (dd, J = 9.6, 9.6, 1H), 1.78 (m, 1H), 1.64–1.56 (m, 2H),
1.01 (d, J = 6.6, 3H); 13C NMR(75 MHz, CD3OD): δ 76.8, 75.0, 74.3, 71.1, 35.9,
33.1, 18.6. ESIMS: m/z 185 [M + Na]+; HRMS: calcd for C7H14O4Na = 185.07805,
[M + Na]+, found 185.07843.
Glycosidase inhibitory study. These assays were performed with fixed concen-
tration of substrate (1.6 mM) in sodium phosphate buffer (0.05 M, pH 6.8) and
enzyme (100 uL, 1mg/mL). The substrate solution (2 mL) was pre-incubated with
compound for 1 min, and the reaction was started by the addition of the enzyme and
the activity was followed for 5 min at 405 nm. Increasing amount of the inhibitors
at fixed enzyme and substrate concentrations, typical dose-response curves were
observed for both inhibitors. The data was analyzed by the following equation:
Y = Bottom + (Top-Bottom)/(1 + 10ˆ((LogIC50-X)∗HillSlope))
Where Y is inhibition% and X is log [inhibitor].
Acknowledgments
We thank Dr. Nitin W. Fadnavis, Natural Product Chemistry division, for helping in glycosidase
inhibition studies and Director, CSIR-IICT for the constant support and encouragement.
Funding
G.R and M.V.R thank CSIR, New Delhi for financial support as part of XII Five Year plan Pro-
gramme under title DENOVA 0205 and ORIGIN.
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