(50 mL), taken up in 2.5 M aqueous NH4OH (20 ml) and the
mixture stirred slowly for 1 h. The suspension was then filtered
and the resin rinsed with 2.5 M aqueous NH4OH (200 mL). The
resulting solution was lyophilised and the residue obtained was
purified by flash column chromatography on deactivated silica
gel eluting with CH2Cl2–MeOH–NH4OH (gradient from 95 : 4
: 1 to 89 : 10 : 1) to give (−)-lentiginosine (1) (22 mg, 0.14 mmol,
67% yield). Rf = 0.33 (solvent CH2Cl2–MeOH–NH4OH, 90 : 9
: 1). [a]2D5 −2.0 (c 1.01 in MeOH); mmax (film)/cm−1: 3285 (O–H);
dH (400 MHz, CD3OD) 1.19–1.35 (m, 4H, H-6ꢀ, H-7ꢀ and 2 ×
O-H), 1.48–1.70 (m, 2H, H-5ꢀ and H-8ꢀ), 1.79–1.88 (m, 2H, H-7
and H-8), 1.95–2.09 (m, 2H, H-5 and H-6), 2.70 (AB of an ABX,
75.4 (C-4), 127.4, 127.5 (C-6 and C-5), 128.8, 128.9, 129.0 (CH
arom.), 138.8 (Cquat. arom.); HRMS (DCI/NH3) m/z: Calc.
for C14H20NO3 250.1443, found 250.1447.
(1R,2R)-1-[(2R)-Pyrrolidin-2-yl]propane-1,2,3-triol (21)
Following the catalytic hydrogenation procedure described
above for 18, dihydropyrrole 20 (60 mg, 0.24 mmol) gave after
purification pyrrolidine 21 (35 mg, 0.22 mmol, 92% yield). Rf =
0.18 (EtOAc–Et2O–MeOH, 80 : 10 : 10 in a saturated atmosphere
of NH3). [a]2D5 +7.8 (c 1.80 in MeOH); mmax (film)/cm−1: 3378 (O–
H and N–H); dC (63 MHz, CD3OD) 26.3, 28.3 (C-5 and C-6),
47.1 (C-7), 62.3 (C-4), 64.6 (C-1), 73.2, 73.8 (C-3 and C-2); MS
(DCI/NH3) m/z: 162 (MH+, 100%).
2H, 3JH1H2 = 1.4 Hz, 3JH1 H2 = 7.2 Hz and 2Jgem = 10.8 Hz, 2 ×
ꢀ
H-1) Dda − db = 130.0 Hz, 2.96–3.02 (m, 1H, H-4), 3.63 (dd,
1H, 3JH3H2 = 3.4 Hz and 3JH3H4 = 8.4 Hz, H-3), 3.96 (ddd, 1H,
3
JH2H1 = 1.5 Hz, 3JH2H3 = 3.4 Hz and 3JH2H1 = 7.2 Hz and H-2);
(1R,2R,7aR)-Hexahydro-1H-pyrrolizine-1,2-diol (2)
ꢀ
dC (100 MHz, CD3OD) 25.8 (C-6), 26.6 (C-7), 30.3 (C-5), 55.4
(C-8), 63.8 (C-1), 72.0 (C-4), 78.5 (C-2), 86.0 (C-3); HRMS (EI)
m/z: Calc. for C8H15NO2 157.1102, found 157.1101.
Using the Appel cyclisation procedure described above for the
preparation of the compound 1, pyrrolizidine 2 was obtained
(18 mg, 0.90 mmol, 68% yield) from 21 after purification by
flash column chromatography on deactivated silica gel eluting
with CH2Cl2–MeOH–EtOH–NH4OH (gradient from 60 : 10 :
20 : 10 to 50 : 20 : 20 : 10). Rf = 0.27 (solvent CH2Cl2–MeOH–
EtOH–NH4OH, 50 : 20 : 20 : 10). [a]2D5 +7.6 (c 1.28 in MeOH);mmax
(film)/cm−1: 3465 (O–H); dH (400 MHz, CD3OD) 1.78–1.87 (m,
1H, H-6ꢀ), 1.93–2.09 (m, 2H, H-5ꢀ and H-6), 2.10–2.20 (m, 1H,
H-5), 2.90–3.23 (m, 1H, H-7ꢀ), 3.25–3.28 (m, 1H, H-7), 3.19
ꢀ
(2R,3R,4R)-4-[Allyl(benzyl)amino]hex-5-ene-1,2,3-triol (19)
To a solution of 11 (200 mg, 0,84 mmol) in THF–H2O (4 : 2)
were successively added allyl bromide (0.291 lL, 3.36 mmol)
and potassium carbonate (697 mg, 5,04 mmol). After stirring
for 48 h at room temperature, the aqueous phase was extracted
with CH2Cl2 (3 × 20 ml) and then with EtOAc (2 × 15 mL).
The combined organic layers were successively washed with
water and brine, dried over Na2SO4, filtered, and concentrated
under reduced pressure. The crude product was purified by flash
column chromatography on deactivated silica gel eluting with
petroleum ether–Et2O–AcOEt (gradient from 60 : 10 : 30 to 30
: 10 : 60) to give 19 (197 mg, 0.71 mmol, 85% yield). Rf = 0,22
(AB of an ABX, 2H, 3JH1 H2 = 4.4 Hz, 3JH1H2 = 5.2 and 2Jgem
=
11.60 Hz, 2 × H-1) Dda − db = 230.0 Hz, 3.55–3.63 (m, 1H, H-4),
3.88–3.95 (m, 1H, H-3), 4.13–4.23 (m, 1H, H-2); dC (100 MHz,
CD3OD) 28.0 (C-6), 32.1 (C-5), 58.9 (C-7), 61.0 (C-1), 75.0 (C-
4), 80.0 (C-2), 82.8 (C-3); HRMS (EI) m/z: Calc. for C7H13NO2
143.0946, found 143.0950.
(solvent petroleum ether–Et2O–AcOEt, 30 : 10 : 60). [a]2D5 −2.8
−1
=
(c 1.00 in CHCl3); mmax (film)/cm : 3465 (O–H), 1489 (C C);
References
dH (250 MHz, CDCl3) 2.91 (dd, 1H, 3JH7 H8 = 8.2 Hz and 2Jgem
=
ꢀ
14.0 Hz, m, H-7ꢀ), 3.20–3.36 (m, 2H, H-4 and H-7), 3.48–3.60
1 T. Ayad, Y. Ge´nisson and M. Baltas, Curr. Org. Chem., 2004, 8,
1211–1233 and references cited therein.
2 M. Mammen, S.-K. Choi and G. M. Whitesides, Angew. Chem., Int.
Ed., 1998, 37, 2754–2794.
2
(m, 2H, 2 × H-1), 3.58 (ABq, 2H, Jgem = 13.4 Hz, NCH2Ph)
Dda − db = 137.5 Hz, 3.79 (dd, 1H, 3JH3H2 = 3.0 Hz and 2JH3H4
=
9.1 Hz, H-3), 4.03–3.98 (m, 1H, H-2), 4.71–4.85 (m, 3H, O–H),
5.17–5.32 (m, 3H, H-6ꢀ and 2 × H-9), 5.51 (dd, 1H, 2Jgem = 2.0 Hz
3 A. E. Stu¨tz, in Iminosugars as glycosidases inhibitors: Nojirimycin and
beyond, Wiley-VCH Verlag GmbH, 1998.
4 M. Bols, Acc. Chem. Res., 1998, 31, 1–8; T. D. Heightman and A. T.
Vasella, Angew. Chem., Int. Ed., 1999, 38, 750–770 and references
cited therein.; D. L. Zechel and S. G. Withers, Acc. Chem. Res., 2000,
33, 11–18.
5 (a) T. Ayad, Y. Ge´nisson, M. Baltas and L. Gorrichon, Synlett, 2001,
866–868; (b) K. Marotte, T. Ayad, Y. Genisson, G. S. Besra, M. Baltas
and J. Prandi, Eur. J. Org. Chem., 2003, 2557–2565; (c) T. Ayad,
Y. Genisson, S. Broussy, M. Baltas and L. Gorrichon, Eur. J. Org.
Chem., 2003, 2903–2910.
3
and JH6H5 = 10.2 Hz, H-6), 5.77–5.93 (m, 2H, H-5 and H-8),
7.20–7.37 (m, 5H, H-Ph); dC (63 MHz, CDCl3) 53.6 (C-7), 55.6
(NCH2Ph), 63.9 (C-4), 64.3 (C-1), 71.1 (C-2), 71.5 (C-3), 118.1,
121.6 (C-6 and C-9), 127.3, 128.5, 129.1 (CH arom.), 132.7 (C-
8), 136.0 (C-5), 139.0 (Cquat. arom.); HRMS (DCI/NH3) m/z:
Calc. for C16H24NO3 278.1756, found 278.1756.
(1R,2R)-1-[(2R)-1-Benzyl-2,5-dihydro-1H-pyrrol-2-yl]propane-
6 For a preliminary communication see: T. Ayad, Y. Genisson, M.
Baltas and L. Gorrichon, Chem. Commun., 2003, 582–583.
7 R. Appel and R. Kleinstu¨ck, Chem. Ber., 1974, 107, 5–12.
8 For a review of the use of RCM in synthesis of bicyclic azasugars
see: U. K. Pandit, H. S. Overkleeft, B. C. Borer and H. Biera¨ugel,
Eur. J. Org. Chem., 1999, 959–968.
1,2,3-triol (20)
To a solution of diene 19 (100 mg, 0,36 mmol) in freshly distilled
CH2Cl2 (10 mL) was added benzylidene-bis (tricyclohexylphos-
phine)dichlororuthenium (Grubbs I catalyst) (25 mg, 8% mol)
at room temperature. The resulting mixture was refluxed in an
inert atmosphere until no remaining starting material could be
detected by TLC (ca. 5 h). The reaction mixture was then allowed
to cool to room temperature and the solvent was removed under
reduced pressure. The residue thus obtained was purified by
flash column chromatography on deactivated silica gel eluting
with AcOEt–petroleum ether–MeOH (gradient from 60 : 30 :
10 to 80 : 10 : 10) to give 20 (63 mg, 0.25 mmol, 70% yield).
Rf = 0,23 (solvent AcOEt–petroleum ether–MeOH, 80 : 10 :
10). [a]2D5 +60.2 (c 2.80 in CHCl3); mmax (film)/cm−1: 3465 (O–H),
9 For isolation of (−)-lentiginosine see: I. Pastuszak, R. J. Molyneux,
L. F. James and A. D. Elbein, Biochemistry, 1990, 29, 1886–1891. For
chiral pool syntheses see: (a) H. Yoda, H. Kitayama, T. Katagiri and
K. Takabe, Tetrahedron: Asymmetry., 1993, 4, 1455–1456; (b) Mk
Gurjar, L. Ghosh, M. Syamala and V. Jayasree, Tetrahedron Lett.,
1994, 35, 8871–8872; (c) R. Giovannini, E. Marcantoni and M.
Petrini, J. Org. Chem., 1995, 60, 5706–5707; (d) A. Goti, F. Cardona
and A. Brandi, Synlett, 1996, 761–763; (e) H. Yoda, M. Kawauchi
and K. Takabe, Synlett, 1998, 137–138; (f) A. E. McCaig, K. P.
Meldrum and R. H. Wightman, Tetrahedron, 1998, 54, 9429–9446;
(g) D.-C. Ha, C.-S. Yun and Y. Lee, J. Org. Chem., 2000, 65, 621–
623; (h) H. Yoda, H. Katoh, Y. Ujihara and K. Takabe, Tetrahedron
Lett., 2001, 42, 2509–2512; (i) J. Rabiczko, Z. Urban´czyk-Lipkowska
and M. Chmielewski, Tetrahedron, 2002, 58, 1433–1441; (j) K. L.
Chandra, M. Chandrasekhar and V. K. Singh, J. Org. Chem., 2002,
67, 4630–4633; (k) Y. Ichikawa, T. Ito, T. Nishiyama and M. Isobe,
Synlett, 2003, 7, 1034–1036. For asymmetric syntheses see:; (l) S.
Nukui, M. Sodeoka, H. Sasai and M. Shibasaki, J. Org. Chem., 1995,
60, 398–404; (m) M. O. Rasmussen, P. Delair and A. E. Greene,
1489 (C C); dH (250 MHz, CD3OD) 3.20–3.31 (m, 1H, H-7ꢀ),
=
3.54–3.69 (m, 3H, 2 × H-1, H-7), 3.71 (dd, 1H, 3JH3H2 = 2.0 Hz,
3JH3H4 = 4.0 Hz, H-3), 3.84 (td, 1H, JH2H3 = 2.0 Hz, JH2H1
=
3
3
6.0 Hz, H-2), 3.98 (ABq, 2H, 2Jgem = 13.0 Hz, NCH2Ph), Dda −
db = 203.0 Hz, 4.05–4.13 (m, 1H, H-4), 5.75–5.87 (m, 2H, H-
5 and H-6), 7.24–7.39 (m, 5H, H–Ph); dC (63 MHz, CD3OD)
60.6 (C-7), 61.2 (NCH2Ph), 65.7 (C-1), 71.2 (C-2), 72.9 (C-3),
2 6 3 0
O r g . B i o m o l . C h e m . , 2 0 0 5 , 3 , 2 6 2 6 – 2 6 3 1