Total synthesis of (-)-lentiginosine

Article abstract of DOI:10.1016/j.tetasy.2008.02.017

The total synthesis of (-)-lentignosine is achieved from d-glyceraldehyde in good yields involving a Sharpless asymmetric epoxidation and a one-pot indolizidine construction strategy.

Full text of DOI:10.1016/j.tetasy.2008.02.017

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 746–750
Total synthesis of (ꢀ)-lentiginosine
S. Chandrasekhar,* B. V. D. Vijaykumar and T. V. Pratap
Organic Division-I, Indian Institute of Chemical Technology, Hyderabad 500 007, India
Received 1 February 2008; accepted 14 February 2008
Abstract—The total synthesis of (ꢀ)-lentignosine is achieved from D-glyceraldehyde in good yields involving a Sharpless asymmetric
epoxidation and a one-pot indolizidine construction strategy.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
OH
OH
H
N
H
The design and synthesis of glycosidase inhibitors has been
a topic of current research among various research groups.
Most glycosidase inhibitors fall under ‘sugar mimics’, typ-
ically represented by polyhydroxylated piperidines, pyrro-
lidines, indolizidines and nortropane alkaloids. These
mimics have been used as potential therapeutic agents in
antidiabetic therapy, tumour metastasis, viral infections
(mainly as anti-HIV agents)1 and genetic disorders.2 As a
result of these properties, all of the hydroxylated alkaloids
(more than 100 of these have already been isolated from
both plants and microorganisms) have attracted special
attention from both biologists and chemists. The large
number of synthetic efforts has culminated in the total syn-
thesis of several of these natural products and their ana-
OH
OH
N
1
2
(-)-lentiginosine
(+)-lentiginosine
Figure 1. Structures of (ꢀ) and (+)-lentiginosine.
mediate 4 in over 90% yield. The 4-(p-methoxybenzyl)
butyl iodide 5 was prepared by following the literature pro-
cedure.9 The acetylenic anion in 4 was treated with 5 to give
the alkylated 3-octyne derivative 6 in 52% yield.10
The deprotection of the cyclohexylidene protection in 6 was
straightforward in the presence of dilute HCl to furnish 1,2-
diol 7. By taking advantage of the propargylic alcohol, com-
pound 7 was subjected to LiAlH4 reduction in ether at 0 °C
to rt for 4 h to furnish (E)-allylic alcohol 8 whose geometry
was proven by NMR spectroscopy (1H NMR chemical shift
on C-4: d 5.74, dtd, J = 0.9, 6.8, 15.5 Hz; 1H NMR chemical
shift on C-3: d 5.43, tdd, J = 1.3, 6.6, 15.5 Hz). The required
additional stereogenic centres were derived by Sharpless
asymmetric epoxidation using (+)-diisopropyl L-tartrate,
which is in accordance with the existing chirality11 to realize
mismatched epoxy diol 9 in about 65% yield. The chiral
HPLC of this compound confirmed the enantiomeric purity
to be greater than 95%, whereas simple epoxidation with m-
CPBA ended up with 6:4 non-separable diastereomeric mix-
ture. The selective tosylation of the 1° alcohol group in 9
was achieved using p-toluenesulfonylchloride, pyridine
and catalytic Bu2SnO in 90% yield. The displacement of
the tosyl group by azide was achieved using NaN3 in
DMF at 80 °C to furnish the azido-alcohol 10. The
logues.3,4 (+)-Lentiginosine
2
has attracted much
attention from synthetic chemists and work involved with
this target has recently been reviewed.5
(ꢀ)-Lentiginosine 1 has shown a selective inhibition of
amyloglucosidases that hydrolyze 1,4- and 1,6-a-glucosidic
linkages.3a,6 Herein, we report a new chiron approach to-
wards the synthesis of 1 (Fig. 1) starting from dioxa-spiro
derivative 4, which was obtained from glyceraldehyde
derivative 37 (Scheme 1).
2. Results and discussion
Aldehyde 3 was subjected to a Corey–Fuchs protocol8
using TPP, CBr4 and n-BuLi to furnish acetylenic inter-
*
Corresponding author. Tel.: +91 40 27193210; fax: +91 40 27160512;
e-mail: srivaric@iict.res.in
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.02.017

S. Chandrasekhar et al. / Tetrahedron: Asymmetry 19 (2008) 746–750
747
OH
O
N3
(-)-lentiginosine, 1
OTs
12
O
OMPM
O
+
O
I
O
OMPM
4
6
5
Scheme 1. Retrosynthesis of (ꢀ)-lentiginosine.
OH
a
d
b
c
O
O
O
O
OH
OMPM
O
O
O
7
4
3
OMPM
6
OH
OH
OH
O
O
e
g
f
OMPM
OMPM
OH
OMPM
OH
N3
OH
10
9
8
OH
OH
O
O
i
h
1
OTs
11
N3
12
N3
Scheme 2. Reagents and conditions: (a) TPP, CBr4, CH2Cl2, 0 °C to rt, 90%; (ii) n-BuLi, Et2O, 0 °C to rt, 79%; (b) n-BuLi, THF, 5, ꢀ78 °C, 52%; (c) 1:1
CH3CN/1 M HCl, rt, 98%; (d) LiAlH4, Et2O, 0 °C to rt, 70%; (e) (+)-DIPT, Ti(iOPr)4, TBHP, CH2Cl2, ꢀ20 °C, 72 h, 65%; (f) (i) TsCl, Py, Bu2SnO, rt,
84%; (ii) NaN3, DMF, 80 °C, 90%; (g) DDQ, THF/H2O (1:1) 62%; (h) TsCl,Py, 0 °C, 57%; (i) 10 mol % Lindlar’s catalyst, MeOH, rt, 3 h then two drops
methanolic KOH, 39%.
deprotection of the MPM group was achieved using DDQ
to form the primary alcohol 11, which was again tosylated
to give 12 using 1 equiv of p-toluenesulfonylchloride and
pyridine as solvent. The reduction of azido group using
Lindlar’s catalyst in MeOH resulted in the one-pot reduc-
tion, a double intramolecular nitrogen triggered epoxide
opening (a 5-endo-tet ring closure)12 and tosyl displacement
in a clean indolizidine construction (Scheme 2). This al-
lowed us to complete the total synthesis of (ꢀ)-lentigino-
sine, whose analytical data were in complete agreement
with the reported ones.3
4. Experimental
4.1. General
All solvents and reagents were purified by standard tech-
niques. Crude products were purified by column chromato-
graphy on silica gel of 60–120 mesh. IR spectra were
recorded on Perkin–Elmer 683 spectrometer. Optical rota-
tions were obtained on Jasco Dip 360 digital polarimeter.
1H and 13C NMR spectra were recorded in CDCl3 solution
on a Varian Gemini 200 and Brucker Avance 300. Chemi-
cal shifts were reported in parts per million with respect to
internal TMS. Coupling constants (J) are quoted in Hertz.
Mass spectra were obtained on an Agilent Technologies
LC/MSD Trap SL.
3. Conclusions
In conclusion, we have achieved a higly efficient stereose-
lective synthesis of (ꢀ)-lentiginosine. The key steps being
‘mismatched Sharpless asymmetric epoxidation’ and one-
pot indolizidine construction by Lindlar’s catalytic
hydrogenation.
4.1.1. (S)-1,2-Cyclohexylidenedioxybut-3-yne 4. Triphenyl
phosphine (9.18 g, 35.0 mmol) was dissolved in CH2Cl2
(85 mL) and cooled to 0 °C. To the cooled solution was

748
S. Chandrasekhar et al. / Tetrahedron: Asymmetry 19 (2008) 746–750
added CBr4 (5.85 g, 17.6 mmol) in one portion, and the
mixture was stirred for 1 h, after which a solution of 3
(2.52 g, 14.9 mmol) in 20 mL of CH2Cl2 was added in
one portion, and the mixture was stirred for 1 h. The solu-
tion was concentrated in vacuo, and the residual solid was
purified via silica gel column chromatography eluted with
hexanes/EtOAc (9:1) to give dibromoalkene (4.378 g, 90%
yield) as a light brownish oil.
ture. The CH3CN in the reaction mixture was removed
under vacuum. Then, it was diluted with ethyl acetate
(50 mL) and after separation of the layers, the aqueous
layer was further extracted into ethyl acetate (30 mL ꢁ 3).
The combined organic layers were washed with brine
(30 mL) and dried over anhydrous Na2SO4. After the evap-
oration of the solvent, the residue was purified on silica gel
column eluted with hexanes/EtOAc (1:1) to give diol 8
25
(2.32 g, 98% yield) as a viscous liquid; ½aꢂD ¼ þ11:0 (c
This vinyldibromide (1.21 g, 3.7 mmol) was dissolved in
THF (20 mL) and subsequently cooled to ꢀ78 °C. To this
was added a solution of n-BuLi (2.5 M in hexanes) (3.6 mL,
9.0 mmol) over 15 min via a syringe. The reaction was then
allowed to proceed at ꢀ78 °C for 30 min, after which the
solution was warmed to room temperature and stirred for
1 h. The mixture was then cooled to 0 °C, quenched with
H2O (100 mL) and extracted into EtOAc (100 mL ꢁ 2).
The combined organic layers were dried with MgSO4, fil-
tered and concentrated in vacuo. Purification via silica
gel chromatography eluted with hexanes/Et2O (9.5:0.5)
1.2, CHCl3): IR (neat): m 3434, 2924, 2857, 1623, 1514,
1246, 1084, 1032 cmꢀ1 1H NMR (CDCl3, 300 MHz): d
;
7.18 (d, J = 8.3 Hz, 2H), 6.82 (d, J = 8.3 Hz, 2H), 4.39 (s,
2H), 4.34–4.30 (m, 1H), 3.79 (s, 3H), 3.65–3.50 (m, 2H),
3.42 (t, J = 6.0 Hz, 2H), 2.22 (dt, J = 6.7, 1.5 Hz, 2H),
2.10 (br s, 1H), 2.01 (br s, 1H), 1.72–1.53 (m, 4H); 13C
NMR (CDCl3, 75 MHz): d 159.1, 130.4, 129.2, 113.7,
86.6, 78.2, 72.5, 69.3, 66.7, 63.3, 55.2, 28.7, 25.2, 18.4;
ESIMS: m/z 301 (M+Na)+; HRMS calcd for C22H30O4Na:
301.1415 (M+Na)+, found: 301.1417.
gave 4 (0.49 g, 79% yield) as a low boiling light yellow li-
4.1.4. (2S,3E)-8-[(4-Methoxybenzyl)oxy]-3-octene-1,2-diol
8. In a clean and dry round-bottom flask, LiAlH4
(0.27 g, 7.1 mmol) was dissolved in dry ether (5 mL) and
cooled to 0 °C. To it was added diol 7 (1.0 g, 3.6 mmol)
in Et2O (10 mL). The mixture was stirred for 2 h and
quenched with saturated aq Na2SO4 (3 mL) and stirred
for 3 h. Then it was filtered through Celite and washed with
ethyl acetate (20 mL ꢁ 2). The combined organic layers
were washed with water (25 mL), brine (20 mL), dried over
Na2SO4 and the solvent was evaporated in vacuo. The res-
idue obtained was purified by column chromatography on
silica gel eluted with hexanes/EtOAc (1:1) to give the allylic
25
quid; ½aꢂD ¼ þ39:0 (c 1.0, CHCl3); IR (neat): m 3440,
2923, 1636, 1216, 1045, 761 cmꢀ1 1H NMR (CDCl3,
;
300 MHz): d 4.71–4.67 (m, 1H), 4.17 (dd, J = 8.3, 6.8 Hz,
1H), 4.15 (dd, J = 8.3, 6.0 Hz, 1H), 2.48 (d, J = 2.2 Hz,
1H), 1.76 (m, 2H), 1.63 (m, 6H), 1.42 (m, 2H); 13C NMR
(CDCl3, 75 MHz): d 111.2, 81.6, 73.7, 69.5, 64.9, 36.4,
36.1, 25.1, 23.8; ESIMS: m/z 167 (M+H)+ detected in
APCI-scan only.
4.1.2.
(2S)-2-{6-[(4-Methoxybenzyl)oxy]-1-hexynyl}-1,4-
dioxaspiro[4.5]decane 6. To a cold (ꢀ78 °C), stirred solu-
tion of 1-alkyne (1.99 g, 12.0 mmol) in THF (50 mL) was
added n-BuLi (1.6 M in hexanes) (6.87 mL, 11 mmol).
The solution was allowed to warm to room temperature
before adding alkyl halide (3.2 g, 10 mmol). The reaction
mixture was heated at gentle reflux and stirred until all of
the alkyl halide was consumed (TLC, 9 h). The mixture
was cooled to 0 °C and quenched with saturated NH4Cl
(70 mL). Standard work-up with ether (50 mL ꢁ 2) pro-
vided a crude material, which was purified by flash
chromatography eluted with hexanes/EtOAc (95:5) to give
diol 8 (0.70 g, 70% yield) as a yellowish oily liquid;
25
½aꢂD ¼ þ7:2 (c 1.0, CHCl3); IR (neat): m 3423, 2925, 2856,
2364, 1742, 1621, 1513, 1457, 1247, 1087, 1030, 761 cmꢀ1
;
1H NMR (CDCl3, 300 MHz): d 7.24 (d, J = 8.7 Hz, 2H),
6.88 (d, J = 8.7 Hz, 2H), 5.74 (dtd, J = 0.9, 6.8, 15.5 Hz,
1H), 5.43 (tdd, J = 1.3, 6.6, 15.5 Hz, 1H), 4.42 (s, 2H),
4.19–4.13 (m, 1H), 3.8 (s, 3H), 3.60 (dd, J = 3.6, 11.1 Hz,
1H), 3.48–3.41 (m, 2H), 3.02 (t, J = 7.5 Hz, 1H), 2.45 (br
s, 2H), 2.04 (q, J = 7.1 Hz, 2H), 1.68–1.38 (m, 4H); 13C
NMR (CDCl3, 75 MHz): d 159.1, 133.9, 130.6, 129.2,
128.6, 113.7, 73.1, 72.5, 69.8, 66.5, 55.2, 32.0, 29.2, 25.6;
ESIMS: m/z 303 (M+Na)+; HRMS calcd for C16H24O4Na:
303.1572 (M+Na)+, found: 303.1566.
alkylated 3-octyne derivative 6 (1.88 g, 52% yield) as a light
25
yellowish oily liquid; ½aꢂD ¼ þ24:5 (c 1.2, CHCl3); IR
(neat): m 3449, 2930, 2857, 2368, 1614, 1513, 1246, 1102,
1
926, 821, 765 cmꢀ1; H NMR (CDCl3, 300 MHz): d 7.25
(d, J = 8.7 Hz, 2H), 6.86 (d, J = 8.7 Hz, 2H), 4.72–4.66
(m, 1H), 4.42 (s, 2H), 4.10 (dd, J = 7.8, 6.2 Hz, 1H),
3.81 (m, 4H), 3.44 (t, J = 6.2 Hz, 2H), 2.23 (dt, J = 6.9,
1.9 Hz, 2H), 1.74–1.52 (m, 14H) 13C NMR (75 MHz,
4.1.5. (1R)-1-{(2S,3S)-3-4-[(4-Ethylbenzyl)oxy]butyloxiran-
2-yl}ethane-1,2-diol 9. To a stirred suspension of vaccum-
dried and powdered molecular sieves (4 A) (2.0 g) in
˚
CH2Cl2 (40 mL) were added Ti(OiPr)4 (1.1 mL, 3.6 mmol)
and (+)-diisopropyl L-tartrate (DIPT) (0.98 g, 4.2 mmol)
in CH2Cl2 (6 mL) at ꢀ20 °C. After stirring for 30 min at
the same temperature, diol 8 (0.98 g, 3.5 mmol) was added
to the mixture and kept stirring for 1 h at the same temper-
ature. A solution of tert-butyl hydroperoxide (TBHP) (4 M
in toluene) (960 lL, 3.84 mmol) was added to the mixture
and the mixture was stirred for 72 h at ꢀ20 °C. The reac-
tion was quenched by the addition of water (10 mL) fol-
lowed by acetone (50 mL), and the mixture was filtered
using Celite. The Celite was washed with THF
(100 mL ꢁ 2) and the combined filtrate was dried over
anhydrous Na2SO4, evaporated under reduced pressure
CDCl3):
d 159.1, 130.6, 129.1, 113.7, 110.5, 86.3,
77.6, 72.5, 69.8, 69.4, 65.4, 55.2, 35.7, 35.4, 28.8, 25.1,
25.0, 23.8, 18.5. (ESI-MS): m/z 381 (M+Na)+; HRMS
calcd for C22H30O4Na: 381.2041 (M+Na)+, found:
381.2043.
4.1.3.
(2S)-8-[(4-Methoxybenzyl)oxy]-3-octyne-1,2-diol
7. Into a 250 mL round-bottom flask were added cyclo-
hexylidene acetal (3.4 g, 9.5 mmol) and 20 mL of 1:1
CH3CN/1 M HCl and stirred at room temperature for
about 20 min. The reaction was quenched with solid sodi-
umbicarbonate (5 g, till neutralization) at room tempera-

S. Chandrasekhar et al. / Tetrahedron: Asymmetry 19 (2008) 746–750
749
to leave the residue which was purified by silica gel column
chromatography eluted with hexanes/Et2O (4:1) to afford
4.1.7. 4-((2S,3S)-3-((R)-2-Azido-1-hydroxyethyl)oxiran-2-
yl)butan-1-ol 11. In a 100 mL round bottom flask azidoal-
cohol 10 (212 mg, 0.66 mmol) was dissolved in 5:1 mixture
of CH2Cl2/H2O (10 mL) and DDQ (165 mg, 0.72 mmol)
added at 0 °C and allowed to stir at rt for 3 h. The reaction
was quenched with saturated NaHCO3 and extracted into
CH2Cl2 (10 mL ꢁ 2). The combined organic layers were
dried over Na2SO4 and concentrated in vacuo. The crude
residue was purified by silica gel column chromatography
epoxide 9 (0.67 g, 65% yield) as a light yellow viscous
25
liquid; ½aꢂD ¼ ꢀ12:8 (c 1.0, CHCl3); IR (neat): m 3425,
1
2924, 2857, 1706, 1610, 1253, 1098, 1032, 762 cmꢀ1; H
NMR (CDCl3, 300 MHz): d 7.26 (d, J = 8.3 Hz, 2H),
6.86 (d, J = 8.3 Hz, 2H), 4.42 (s, 2H), 3.79 (s, 3H), 3.7–
3.61 (m, 3H), 3.44 (t, J = 6.0 Hz, 2H), 3.20 (br s, 2H),
2.95 (br s, 1H), 2.82 (br s, 1H), 1.66–1.54 (m, 6H); 13C
NMR (CDCl3, 75 MHz): d 159.0, 130.4, 129.2, 113.7,
72.5, 70.9, 69.6, 64.3, 58.9, 55.6, 55.1, 31.1, 29.3, 22.5.
(ESI-MS): m/z 313 (M+Na)+; HRMS calcd for
C16H24O5Na: 319.1516 (M+Na)+, found: 319.1515.
to afford azidodiol 11 (82 mg, 62% yield) as a viscous yel-
25
low liquid; ½aꢂD ¼ ꢀ11:0 (c 0.25, CHCl3); IR (neat): m
3420, 2924, 2855, 2353, 2102, 1742, 1644, 1515, 1459,
1217, 1173, 1020 cmꢀ1 1H NMR (CDCl3, 300 MHz): d
;
3.89–3.72 (m, 3H), 3.57–3.38 (m, 2H), 3.09–2.96 (m, 1H),
2.9–2.8 (m, 1H), 2.2 (br s, 2H), 1.75–1.45 (m, 6H); 13C
NMR (CDCl3, 75 MHz): d 69.6, 62.8, 58.9, 56.1, 54.5,
31.1, 29.4, 22.6; ESIMS: m/z 224 (M+Na)+; HRMS calcd
for C8H15N3O3Na: 224.1005 (M+Na)+, found: 224.1004.
4.1.6.
(R)-2-Azido-1-((2S,3S)-3-(4-(4-methoxybenzyloxy)
butyl)oxiran-2-yl)ethanol 10. To a solution of 9 (0.27 g,
0.9 mmol) in CH2Cl2 (10 mL) were added Et3N (280 lL,
2.0 mmol) and p-toluenesulfonylchloride (0.19 g, 1.0 mmol)
at 0 °C and allowed to stir for 3 h at room temperature.
After the completion of the reaction, the reaction mixture
was quenched with saturated solution of aq NH4Cl
(20 mL) and extracted into CH2Cl2 (30 mL ꢁ 2). The com-
bined organic layers were washed with water (50 mL),
brine (50 mL), dried over anhydrous Na2SO4 and concen-
trated in vacuo. The crude product was purified by column
chromatography on silica gel eluted with hexanes/EtOAc
4.1.8. 4-((2S,3S)-3-((R)-2-Azido-1-hydroxyethyl)oxiran-2-
yl)butyl 4-methylbenzenesulfonate 12. To a stirred solu-
tion of azidodiol 11 (55 mg, 0.27 mmol) in dry pyridine
(218 lL, 2.7 mmol) was added p-toluenesulfonylchloride
(55 mg, 0.28 mmol) portionwise and stirred for 30 min.
After the completion of the reaction, the mixture was
quenched with a saturated solution of aq CuSO4 (5 mL)
and extracted into CH2Cl2 (5 mL ꢁ 3). The combined
organic layers were dried over anhydrous Na2SO4 and con-
centrated in vacuo. The crude product obtained was puri-
fied by flash column chromatography to afford
(9:1) to afford mono tosyl product of 9 (0.34 g, 84% yield)
25
as a yellow viscous liquid; ½aꢂD ¼ ꢀ6:6 (c 1.0, CHCl3); IR
(neat): m 3434, 2924, 2856, 2353, 2102, 1730, 1620, 1520,
1171, 1025, 760 cmꢀ1 1H NMR (CDCl3, 300 MHz): d
;
compound 12 (55 mg, 57% yield) as yellowish viscous li-
7.81 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 7.22
(d, J = 9.0 Hz, 2H), 6.85 (d, J = 9.0 Hz, 2H), 4.42 (s,
2H), 4.04 (d, J = 6.0 Hz, 2H), 3.88–3.82 (m, 1H), 3.81 (s,
3H), 3.44 (t, J = 6.0 Hz, 2H), 2.95–2.89 (m, 1H), 2.83–
2.80 (m, 1H), 2.48 (s, 3H) 2.25 (br s, 1H), 1.69–1.46 (m,
6H); 13C NMR (CDCl3, 75 MHz): d 159.1, 145.1, 130.6,
129.9, 129.2, 128.7, 128.0, 113.8, 72.5, 70.6, 69.6, 67.8,
57.6, 55.5, 55.2, 31.1, 29.7, 29.4, 22.6; ESIMS: m/z 473
(M+Na)+, HRMS calcd for C23H30O7SNa: 473.1609
(M+Na)+, found: 473.1620.
25
quid; ½aꢂD ¼ þ19:0 (c 1.0, CHCl3); IR (neat): m 3420,
2924, 2855, 2353, 2102, 1742, 1644, 1515, 1459, 1217,
1
1173, 1020, 759, 667 cmꢀ1; H NMR (CDCl3, 300 MHz):
d 7.78 (d, J = 8.3 Hz, 2H), 7.37 (d, J = 8.3 Hz, 2H), 4.03
(t, J = 6.3 Hz, 2H), 3.74 (br s, 1H), 3.43–3.38 (m, 2H),
2.93 (s, 1H), 2.82 (d, J = 3.9 Hz, 1H), 2.46–2.55 (m, 4H),
1.75–1.49 (m, 6H); 13C NMR (CDCl3, 75 MHz): d 145.0,
133.1, 130.0, 128.0, 70.2, 69.5, 58.8, 55.7, 54.3, 30.8, 28.6,
22.0, 21.7; ESIMS: m/z 378 (M+Na)+; HRMS calcd for
C15H21N3O5SNa: 378.1099 (M+Na)+, found: 378.1093.
The above compound (0.34 g, 0.7 mmol) was dissolved in
dry DMF (2 mL), after which was added NaN3 (0.05 g,
0.8 mmol). The mixture was stirred at 80 °C for 3 h. After
the completion of the reaction it was cooled to room tem-
perature and cold water (5 mL) added. Then the compound
was extracted into ether (10 mL ꢁ 2). The combined
organic layers were dried over Na2SO4 and concentrated
in vacuo. The crude product was purified by column
4.1.9. (1R,2R,8aR)-1,2-Dihydroxyindolizidine 1, [(ꢀ)-lentig-
inosine]. To a solution of monotosylate 12 (36 mg,
0.1 mmol) in MeOH (5 mL), Lindlar’s catalyst (0.01 mmol)
was added and stirred under a H2 atmosphere for 3 h. The
reaction mixture was filtered through Celite and washed
with MeOH (5 mL ꢁ 2). The filterate was basified (if neces-
sary) with methanolic KOH (2 drops) and then MeOH was
removed under reduced pressure. The crude residue was
dissolved in H2O (1 mL) and purified by ion-exchange
chromatography (Dowex resin) using 2% ammonia solu-
chromatography on silica gel to afford azidoalcohol 10
25
(0.20 g, 82% yield) as an oily yellow liquid; ½aꢂD ¼ ꢀ8:0
(c 0.5, CHCl3); IR (neat): m 3424, 2923, 2854, 1624, 1462,
1
1216, 760 cmꢀ1; H NMR (CDCl3, 300 MHz): d 7.24 (d,
tion to afford 1 (6 mg, 39% yield) as a white crystalline
25
J = 8.6 Hz, 2H), 6.87 (d, J = 8.6 Hz, 2H), 4.43 (s,
2H), 3.88–3.72 (m, 4H), 3.50–3.35 (m, 4H), 3.0–2.91 (m,
1H), 2.83 (dd, J = 2.3, 3.9 Hz, 1H), 2.0 (br s, 1H),
1.68–1.50 (m, 6H); 13C NMR (CDCl3, 75 MHz): d
159.1, 130.6, 129.2, 113.7, 72.5, 69.6, 69.3, 58.6, 55.9,
55.2, 54.3, 31.1, 29.4, 22.6; ESIMS: 344 (M+Na)+; HRMS
calcd for C16H23N3O4Na: 344.1586 (M+Na)+, found:
344.1575.
solid: mp 106–108 °C (lit.3c 106–107 °C); ½aꢂD ¼ ꢀ3:1 (c
0.5, MeOH); IR (neat): m 3423, 2924, 1638, 1019,
758 cmꢀ1
.
1H NMR (D2O, 300 MHz): d 4.05 (ddd,
J = 7.6, 3.8, 1.6 Hz, 1H), 3.66 (dd, J = 8.7, 3.8 Hz, 1H),
3.01 (br d, J = 10.9 Hz, 1H), 2.85–2.58 (m, 2H), 2.2–2.12
(m, 2H), 1.91–1.85 (m, 1H), 1.73–1.74 (m, 1H), 1.60–1.52
(m, 1H), 1.41–1.27 (m, 1H), 1.25–1.14 (m, 2H); 13C
NMR (D2O, 75 MHz): d 81.8, 75.0, 69.0, 59.8, 52.9, 26.8,

750
S. Chandrasekhar et al. / Tetrahedron: Asymmetry 19 (2008) 746–750
23.5, 22.6; (ESI-MS): m/z 158 (M+H+); HRMS (M+H+)
calcd for C8H16NO2: 158.1181, found: 158.1180.
3. (a) Pastuszak, I.; Molyneux, R. J.; James, L. F.; Elbein, A. D.
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anth, T. Tetrahedron: Asymmetry 2004, 15, 565–570; (e)
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Acknowledgements
B.V.D.V.K. and T.V.P. thank the CSIR, New Delhi for
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