ENANTIOSELECTIVE SYNTHESIS OF (
R
)ꢀ AND (
S
)ꢀ3ꢀMETHYLSPERMIDINES
551
EtOAc–hexane, 2 : 3 (C); CH2Cl2–MeOH–25% Found, %: С 63.37; Н 8.11; N 8.68. C8H24Сl3N3. Calꢀ
NH4OH, 100 : 5.4 : 0.6 (D); nꢀBuOH–AcOH–pyriꢀ
culated, %: С 63.33; Н 8.13; N 8.69. Rf and NMRꢀ
data are identical to that of compound (III).
dine–H2O, 4 : 2 : 1 : 2 (E). Substances on chromatoꢀ
grams were detected by UVꢀabsorbance, Bocꢀderivaꢀ
tives were developed using bromophenol blue and the
compounds with free amino group—using color reacꢀ
tion with ninhydrin.
(
S
)ꢀ
2 mL of 6.7
1.0 g (3.1 mmol) (III) in 5 mL of dry EtОН and after
3 h at 20 the reaction mixture was evaporated to
dryness in vacuo at 20 C. The residue was dissolved in
10 mL of dry ЕtOH, poured into 40 mL dry Et2O and
left for a night at –20 . Separated oil was washed
with dry Et2O (10 mL) and to the residue 4 mL of 2
N
1ꢀ(Benzyloxycarbonyl)ꢀ1,3ꢀdiaminobutane (V).
HCl/EtOH was added to a solution of
М
°С
NMR spectra were registered on a Bruker Avance
500 DRX (Germany) instrument with working freꢀ
quency of 500.1 MHz for 1H nuclei and 125.8 MHz for
13C nuclei. Tetramethylsilane was used as an internal
standard (CDCl3) and sodium 3ꢀtrimethylꢀ1ꢀproꢀ
panesulfonate (D2O). Chemical shifts are given in
ppm, and spinꢀspin coupling constants in Hz. Melting
points were determined in open capillary tubes on
Electrotermals MelꢀTemp 1202D instrument. Analyꢀ
sis of enantiomeric purity of synthesized Rꢀ and Sꢀisoꢀ
mers of 3ꢀMeSpd were performed by HPLC using
chiral column (Phenomex®). Specific rotation was
determined using 341 Polarimeter (PerkinꢀElmer),
solvents and solution concentrations are indicated in
°
°С
М
NaOH and 6 mL of CH2Cl2 were added. Organic
phase was separated, H2Oꢀlayer was extracted with
CH2Cl2 (4
were washed subsequently with H2O (2 mL), 5
NaCl (3 5 mL) and dried (K2CO3). Solvent was disꢀ
tilled off in vacuo and the residue was dried in vacuo
over P2O5/KOH to give ( ) (0.515 g, 75%) as a viscous
oil,
f 0.44 (B), 1H NMR (CDCl3): 7.35–7.26 (5H, m,
×
4 mL) and the combined organic extracts
М
×
V
R
С6Н5), 5.48 (1H, bs, NHCbz), 5.09 (2H, s,
CH2С6Н5), 3.4–3.2 (2H, m, CbzNHCH2), 3.01–2.92
(1H, m, СН3CH), 1.62–1.55 (1H, m, NHCH2CH2),
the text. Elemental analysis was performed with CHN
ꢀ
analyser Carlo Erba 1106.
1.47–1.38 (1H, m, NHCH2CH2), 1.25–1.22 (2H, m,
13
NH2), 1.20 (3H, d,
J
6.5, CH3). C NMR (CDCl3):
(
S
)
ꢀN1ꢀ(Benzyloxycarbonyl)ꢀN3ꢀ(tertꢀbutyloxycarꢀ
bonyl)ꢀ1,3ꢀdiaminobutane (III). To 2.4 g (12.8 mmol)
of )ꢀ
3ꢀ(tertꢀbutyloxycarbonyl)ꢀ1,3ꢀdiaminobuꢀ
tane ( ) and 2.6 g (16 mmol) Et3N in 35 mL of
С6Н6/Et2O (2 : 1) a solution of 2.2 g (13 mmol) CbzCl
in 10 mL of dry C6H6, was added with stirring at +
for 30 min, stirring was continued for 1 h at +8°C and
then for 4 h at 20 . The precipitate was filtered off,
filtrate was washed with H2O (2 mL), 10% citric
acid ( mL), H2O (5 mL), 5 NaCl ( mL)
156.55, 136.85, 128.55, 128.09, 77.40, 77.09, 76.77,
66.60, 45.56, 39.18, 29.75, 24.90.
(
I
S N
(
R
)ꢀ
Prepared as (
IV) and 2.5 mL of 6.7
EtOH that gave (VI) (0.6 g, 75%) as a viscous oil. Rf
and NMRꢀdata are identical to that of compound ( ).
ꢀnitrophenylsulꢀ
N
1ꢀ(Benzyloxycarbonyl)ꢀ1,3ꢀdiaminobutane (VI).
), starting from 1.17 g (3.63 mmol) of
HCl/EtOH in 5 mL of dry
V
(
М
8°С
V
°С
(S)ꢀN N o
1ꢀ(Benzyloxycarbonyl)ꢀ 3ꢀ(
×
5
fonyl)ꢀ1,3ꢀdiaminobutane (VII). A solution of 0.525 g
4
×
4
М
2
×
5
(2.37 mmol) NsCl in 2.5 mL of dry CH2Cl2 was added
and dried (MgSO4). Solvents were distilled off in vacuo
and the residue was purified by flash chromatography
on a silica gel (60 g) eluting with CH2Cl2–МеOH, 98 : 2
that gave semiꢀcrystallized oil, which solidified upon
within 10 min at +4
(2.32 mmol) ( ) and 0.36 mL (8.8 mmol) Et3N in
4.5 mL of dry CH2Cl2 and the reaction mixture was
stirred at +4 C for 1 h and then for 3 h at 20 C. Preꢀ
°
C to a stirred solution of 0.515 g
V
°
°
drying in vacuo (25
°
C/0.5 mm Hg). Recrystallization
cipitate was filtered off, to the filtrate 10 mL of CH2Cl2
was added and thus obtained solution was washed with
from hexane yielded (III) (3.31 g, 81.3%), mp 82.5–
20
H2O (2
(5 mL), 5
×
5 mL), 10% citric acid (4
×
4 mL), H2O
83
Found, %:
culated, %: C 63.33;
°
С
,
Rf 0.72 (А), [α]D +48.9
° (c 2.0, CH2Cl2).
М
NaCl (2 5 mL), dried (MgSO4) and
×
С
63.41; 8.18; N 8.66. C8H24Сl3N3. Calꢀ
Н
concentrated in vacuo. The residue was dried in vacuo
1
Н
8.13; N 8.69. H NMR
over P2O5 to give (VII) (0.93 g, 98.5%) as a viscous oil,
(CDCl3): 7.39–7.27 (5H, m, С6Н5), 5.57 (1H, bs,
NHCbz), 5.12–5.02 (2H, m, CH2С6Н5), 4.34 (1H,
bs, CbzNHCH2), 3.74 (1H, bs, CbzNHCH2), 3.46–
3.41 (1H, m, NHCH2CH2), 3.05ꢀ2.98 (1H, m,
1
Rf 0.22 (C). HꢀNMR (CDCl3): 8.22–8.05 (1H, m,
C6H4NO2), 7.84–7.83 (1H, m, C6H4NO2), 7.73–7.69
(2H, m, C6H4NO2), 7.36–7.31 (5H, m, С6Н5), 5.09
(2H, s, CH2С6Н5), 3.59–3.52 (1H, m, NHCbz),
3.44–3.36 (1H, m, NHCH2CH2), 3.26–3.18 (1H, m,
NHCH2CH2), 1.78–1.77 (1Н, bs, NHNs), 1.58–1.51
(2H, m, NHCH2CH2), 1.26–1.24 (1H, m, СН3CH),
NHCH2CH2), 1.74–1.68 (1H, m, СН3CH), 1.48–1.42
13
NHС(СН3)3), 1.14 (3H, d,
J
6.5, CH3). C NMR
(CDCl3): 128.52, 128.13, 128.04, 77.41, 77.30, 77.09,
76.77, 66.54, 43.83, 37.98, 37.86, 37.17, 28.43, 21.64.
1.04 (3H, d, J
6.5, CH3). 13C NMR (CDCl3): 156.53,
147.96, 136.71, 133.65, 133.00, 130.78, 128.60,
128.18, 125.52, 77.41, 77.10, 76.77, 66.74, 48.76,
37.64, 37.15, 21.67.
1ꢀ(Benzyloxycarbonyl)ꢀ 3ꢀ(
(R)ꢀN N oꢀnitrophenylsulꢀ
fonyl)ꢀ1,3ꢀdiaminobutane (VIII). Prepared as (VII),
starting from 0.6 g (2.7 mmol) of (IV), 0.41 mL
(R)ꢀN N
1ꢀ(Benzyloxycarbonyl)ꢀ 3ꢀ(tertꢀbutyloxyꢀ
carbonyl)ꢀ1,3ꢀdiaminobutane (IV). Prepared as (III),
starting from 1.84 g (9.79 mmol) of (II), 2.02 g
(20 mmol) Et3N and 1.7 g (10 mmol) CbzCl that lead
20
to 2.71 g (86%) of (IV), [[α]D –50.4° (c 2.0, CH2Cl2).
RUSSIAN JOURNAL OF BIOORGANIC CHEMISTRY Vol. 41
No. 5
2015