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J.-M. Vatele / Tetrahedron 60 (2004) 4251–4260
4257
NMR: 1.68 (s, 3H, Me), 1.73 (s, 3H, Me), 1.95 (m, 1H,
CHCH2S), 2.06 (s, 3H, Me), 2.11 (m, 1H, CHCH2S), 2.51(t,
2H, J¼7.5 Hz, CH2S), 3.73 (s, 3H, Me), 4.45 (q, 1H, J¼7.6,
13 Hz, CHCO2Me), 4.55 (d, 2H, J¼7.18 Hz, CH2-
CHvCMe2), 5.31 (brt, 1H, J¼7.15 Hz, CHvCMe2), 5.40
(brs, 1H, NH). 13C NMR: 15.4, 18.0, 25.7, 29.9, 32.1, 52.5,
53.1, 62.1, 118.9, 138.9, 156.1, 172.6. Anal. calcd for
C12H21NO4S: C, 52.34, H, 7.69, N, 5.09, O, 23.24, S, 11.64.
Found: C, 52.28, H, 7.80, N, 5.09, O, 23.16, S, 11.67.
Method A. 0% yield; several products were observed by
TLC (ether).
Method B. The reaction was effected in DMF. After a usual
workup, the solid residue was purified by flash chromato-
graphy on silica gel (ether–petroleum ether, 4:1) to give the
N-protected sugar 4k in 39% yield obtained as a white
crystalline solid, mp 121–124 8C, [a]2D0¼þ17.7 (c 1.2,
CHCl3). IR (KBr): 3350, 1745, 1705, 1530 cm21. 1H NMR:
1.66 (s, 3H, Me), 1.70 (s, 3H, Me), 2.0 (s, 6H, 2OAc), 2.04
(s, 3H, OAc), 2.07 (s, 3H, OAc), 3.80 (m, 1H, H-5), 3.93 (m,
1H, H-2), 4.08 (brd, 1H, J¼12.4 Hz, H-6), 4.27 (dd, 1H,
J¼4.3, 12.4 Hz, H-6), 4.51 (d, 1H, J¼6.7 Hz, CH–
CHvCMe2), 5.05 (t, 1H, J¼9.5 Hz, H-3 or H-4), 5.12–
5.4 (m, 3H, H-3 or H-4, NH, CHvCMe2), 5.65 (d, 1H,
J¼8.5 Hz, H-1). 13C NMR: 18.0, 20.6 (2C), 20.7, 20.8, 25.7,
54.8, 61.8, 62.2, 68.2, 72.5, 72.7, 92.6, 118.9, 138.8, 156.2,
169.5(2C), 170.7, 170.8. Anal. calcd for C20H29NO11: C,
52.28, H, 6.36, N, 3.05, O, 38.31. Found: C, 52.54, H, 6.60,
N, 3.01, O, 37.84.
Method B. 91% yield.
4.2.9. N-(3-Methyl-2-butenyl)oxycarbonyl-L-tryptophan
methyl ester (4i). Method A. Ether–petroleum ether (2:1),
20% yield, crystalline solid, mp 102–104 8C, [a]2D0¼þ51.2
(c 0.5, CHCl3). IR (KBr) 3370, 3340, 1735, 1700, 1620,
1
1540 cm21. H NMR: 1.71 (s, 3H, Me), 1.76 (s, 3H, Me),
3.31 (d, 2H, J¼5.2 Hz, CH2-CHCO2Me), 3.68 (s, 3H, Me),
4.57 (d, 2H, J¼7.04 Hz, CH2–CHvCMe2), 4.72 (q, 1H,
J¼5.5, 13.4 Hz, CHCO2Me), 5.3 (m, 2H, NH and
CHvCMe2), 7.0 (d, 1H, J¼2 Hz, NCH¼), 7.12 (t, 1H,
J¼6.9 Hz, Ar), 7.21(t, 1H, J¼6.7 Hz, Ar), 7.34 (d, 1H,
J¼7.5 Hz, Ar), (7.56 (d, 1H, J¼7.4 Hz, Ar), 8.4 (brs, 1H,
NH). 13C NMR: 18.1, 25.8, 28.0, 52.4, 54.6, 62.2, 109.8,
111.4, 118.6, 118.9, 119.6, 122.2, 123.0, 127.6, 136.3,
138.9, 156.2, 172.7. Anal. calcd for C18H22N2O4: C, 65.44,
H, 6.71, N, 8.48, O, 19.37. Found: C, 65.23, H, 6.92, N,
8.44, O, 19.47.
4.2.12. 1-N-tert-Butoxycarbonyl-3-N-(methyl-2-
butenyl)oxycarbonyl-1,3-diaminopropane (4l). Method
A. Ether–petroleum ether (1.5:1), 80% yield, crystalline
solid, mp 47–48 8C. 1H NMR: 1.42 (s, 9H, C(CH3)3), 1.61
(q, 2H, J¼6.3 Hz, CH2), 1.70 (s, 3H, Me), 1.74 (s, 3H, Me),
3.18 (m, 4H, 2 CH2N), 4.54 (d, 2H, J¼7.12 Hz, CH2–
CHvCMe2), 4.90 (brs, 1H, NH), 5.18 (brs, 1H, NH), 5.32
(brt, 1H, J¼7.11 Hz, CHvCMe2). 13C NMR: 18.0, 25.8,
28.4 (3C), 30.6, 37.2, 37.7, 61.7, 79.3, 119.3, 138.5, 156.4,
157.1. Anal. calcd for C14H26N2O4: C, 58.72, H, 9.15, N,
9.78, O, 22.35. Found: C, 58.50, H, 9.38, N, 9.67, O,
22.37.
Method B. 85% yield.
4.2.10. N 1-(3-Methyl-2-butenyl)oxycarbonyl-L-lysine
methyl ester (4j). Method A. In the case of this substrate,
1 mmol of lysine methyl ester·2HCl was dissolved in
dioxane–H2O (1:1). The reaction mixture was diluted
with water and extracted three times with CH2Cl2.
Chromatography on silica gel of the residue (CH2Cl2–
MeOH, 92:8) gave the N-monoprotected lysine derivative
Method B. 97% yield.
4.2.13. 1-[2-(3-Methyl-2-butenyl)oxyethyl]-4-(3-methyl-
2-butenyl)oxycarbonylpiperazine (4m). To a solution of
the alcohol 4e (0.52 g, 2.1 mmol) in DMF (5 mL), cooled to
250 8C, were successively added NaH (60% dispersion in
mineral oil, 0.104 g, 1.2 equiv) and prenyl bromide
(0.29 mL, 1.5 equiv.). The reaction mixture was allowed
to warm up to 0 8C (90 min), diluted with ether, washed with
water. The aqueous phase was extracted once with ether.
The combined organic phases were dried (Na2SO4) and
concentrated. The residue was purified by chromatography
on silica gel (ether) to give 4m (0.492 g, 74% yield)
obtained as a yellow oil. IR (film): 1700 cm21.1H NMR:
1.67 (s, 3H, Me), 1.71 (s, 3H, Me), 1.75 (s, 6H, 2Me), 2.45
(t, 4H, J¼5.1 Hz, 2 CH2N), 2.59 (t, 2H, J¼5.8 Hz, CH2–
CH2OPre), 3.49 (t, 4H, J¼5.2 Hz, 2CH2N), 3.54 (t, 2H,
J¼5.8 Hz, CH2OPre), 3.97 (d, 2H, J¼6.91 Hz, OCH2–
CHvCMe2), 4.57 (d, 2H, J¼7.05 Hz, NCO2CH2-
CHvCMe2), 5.34 (m, 2H, 2CHvCMe2). 13C NMR: 18.0
(2C), 25.7, 25.8, 43.6, 53.3 (3C), 58.0, 62.3, 67.3, 67.5,
119.5, 121.1, 136.9, 138.0, 155.6. Anal. calcd for
C17H30N2O3: C, 65.77, H, 9.74, N, 9.02, O, 15.46. Found:
C, 65.77, H, 9.90, N, 8.76, O, 15.50.
1
4j, obtained as an oil (51% yield). H NMR: 1.40 (m, 6H,
3CH2), 1.51 (brs, 2H, NH2), 3.1 (dd, 2H, J¼6.3, 12.6 Hz,
CH2N), 3.36 (t, 1H, J¼7.1 Hz, CHCO2Me), 3.64 (s, 3H,
Me), 4.46 (d, 2H, J¼7.12 Hz, CH2-CHvCMe2), 4.96 (brs,
1H, NH), 5.24 (brs, 1H, J¼7.1 Hz, CHvCMe2). Compound
4j was characterized as its hydrochloride salt. To 1 mmol of
4j dissolved in 5 mL of dry ether, cooled to 0 8C, was added
4 N HCl in dioxane (0.35 mL, 1.5 equiv.). After stirring the
reaction mixture for 30 min, the precipitate was filtered and
washed with dry ether to give the hydrochloride salt
(0.363 g, 90% yield). Mp 98–99 8C, [a]2D0¼þ14.6 (c 1.2,
1
H2O). IR (KBr): 3360, 1745, 1690, 1600, 1525 cm21. H
NMR (D2O):1.53 (m, 4H), 1.74 (s, 3H, Me), 1.79 (s, 3H,
Me), 2.0 (m, 2H), 3.15 (t, 2H, J¼6.3 Hz, CH2N), 3.88 (s,
3H, Me), 4.19 (t, 1H, J¼7.1 Hz, CH–CO2Me), 4.57 (d, 2H,
J¼7.02 Hz, CH2–CHvCMe2), 5.38 (brt, 1H, J¼7.05 Hz,
CHvCMe2). 13C NMR: 19.9, 24.0, 27.6, 31.0, 32.0, 42.5,
55.4, 56.1, 64.8, 120.7, 143.5, 151.2, 173.3. Anal. calcd for
C13H25ClN2O4: C, 50.56, H, 8.16, Cl, 11.48, N, 9.07.
Found: C, 50.87, H, 8.38, Cl, 11.50, N, 9.02.
Method B. 81% yield.
4.2.14. 1-(3-Methyl-2-butenyl)-4-(benzyloxycarbonyl)-
piperidine (4n). To a solution of the acid 4f (0.3 g,
1.2 mmol) in acetonitrile (3 mL), cooled to 0 8C, was added
DBU (0.21 mL, 1.16 equiv.). After stirring for 15 min at
4.2.11. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(3-methyl-2-
butenyl)oxycarbonylamino-b-D-glucopyranose
(4k).