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7.0 Hz, H-3), 3.98 (2H, br t, J(H,H) = 7.5 Hz, H-10),
4.21 (2H, tq, J(H,H) = 8.1 Hz and 1.8 Hz, H-5), 8.73
(1H, m, J(H,H) = 1.5 Hz, H-2); dC (D2O) 19.1 (C-4),
23.2 and 23.5 (C-20 and C-30), 35.6 (C-3), 38.6 (C-40),
53.0 (C-10), 58.7 (C-5), 181.3 (C-2); m/z (FAB, 3-nitro-
4.8.19. N-(Boc-glycyl)-N0-Boc-putrescine. Boc-putrescine
(5.65 g, 30 mmol) dissolved in dichloro-methane
(300 mL) was added slowly to a stirred mixture of
Boc-glycine (5.35 g, 30 mmol) and dicyclohexylcarbodi-
imide (6.80 g, 33 mmol) cooled to 0 ꢁC. The stirred mix-
ture was kept at 0 ꢁC for 1 h and then at ambient
temperature for 24 h, whereupon the precipitated di-
cyclohexylurea was filtered off and washed with dichloro-
methane. Washing with saturated NaHCO3 (30 mL),
cold 2 M NaHSO4 (30 mL) and water (2 · 30 mL) en-
sured removalof unreacted Boc-glycine and Boc-putres-
cine. The organic phase was dried over MgSO4 and the
solvent evaporated. Minor impurities of dicyclohexylu-
rea were removed by dissolving the residue in ether fol-
lowed by filtration and evaporation. Recrystallisation
from ether afforded the desired compound as colourless
crystals (8.16 g, 79%), mp 79–80 ꢁC. (Found: C, 55.67;
H, 9.21; N, 12.08. C16H31N3O5 requires C, 55.63; H,
9.05; N, 12.16%); mmax (KBr)/cmꢂ1 3349vs and 3267vs
(mNH), 3053m, 2978s, 2940m, 2871w, 1718vs (mCO),
1695vs (mCO), 1657vs (mCO), 1555 (dNH), 1381s,
1364m, 1294vs, 1251vs, 1181vs, 1134s; dH (CDCl3)
1.37 (18H, s, CH3), 1.44 (4H, m, 2 · CH2), 3.04 (2H, t,
J(H,H) = 6.1 Hz, CH2–N), 3.25 (2H, q, J(H,H) =
5.3 Hz, CH2–N), 3.71 (2H, s, N–CH2–CON), 4.72 (1H,
s, NH), 5.40 (1H, s, NH), 6.57 (1H, s, NH); dC (CDCl3)
26.4, 27.3, 28.2, 39.0, 40.0, 44.2, 79.1, 80.0, 156.0, 169.4;
m/z (FAB) 346 ([M+H]+), 691 ([(2 · M)+H]+).
benzylacloho)l 141.11 ([C
1,6-diazabicyclo[5.3.0]decane in gas phase.
8H16N2+H]+). Analyses as
4.8.16. 1,6-Diazabicyclo[5.3.0]decane. 2 M HCl(5.92
mL, 11.84 mmol) was added to a solution of 5,10-di-
azadecanaldiethylacetal(1.25 g, 5.38 mmo)l in water
(25 mL). The solution was stirred for 25 min at rt, fol-
lowed by addition of 1 M K2CO3 (25 mL). Extraction
with CH2Cl2 (3 · 25 mL), followed by drying over
K2CO3, and evaporation of the solvent afforded the
bicyclic aminal (0.47 g, 62%) as a colourless oil. dH
(CDCl3, 0 ꢁC) 1.40–1.50 (1H, m), 1.60–1.87 (6H, m),
1.94–2.30 (1H, vbr s, NH), 2.12–2.22 (1H, m), 2.44–
2.54 (2H, m), 2.73–2.81 (1H, m), 2.88–3.02 (3H, m),
3.61 (1H, t, J(H,H) = 7.3 Hz, H-1); dC (75 MHz,
CDCl3) 22.0, 26.7, 30.4, 33.9, 47.3, 53.7, 54.6, 78.9; dH
(D2O, 2 ꢁC) 1.10 and 1.83 (2H, br s, H-2), 1.28 and
1.40 (6H, br s, H-3, H-7, H-8), 2.25 and 2.42 (4H, br
s, H-4, H-6), 2.25 and 2.59 (2H, br s, H-9), 3.37 (1H,
br t, J(H,H) = 6.4 Hz, H-1); dC (D2O, 2 ꢁC) 21.5 and
25.4 and 28.8 (C-3, C-7, C-8), 32.4 (C-2), 46.5 (C-9),
51.9 and 53.4 (C-4, C-6) 77.4 (C-1); dC (75 MHz,
CD3OD) 23.4, 27.7, 31.0, 34.5, 48.7, 54.3, 55.7, 80.1;
m/z (EI) 140 (M+, 65%), 139 (59, M–H), 83 (100).
4.8.20. N-(2-Aminoacetyl)-putrescine dihydrochloride. N-
(Boc-glycyl)-N0-Boc-putrescine (4.14 g, 12 mmol) was
dissolved in dichloromethane (40 mL), cooled to 0 ꢁC
and treated with TFA (9.18 mL, 0.12 mol). The reaction
mixture was stirred at room temperature for 30 min and
then evaporated to dryness leaving a slightly pink oil. In
order to remove excess TFA, toluene (50 mL) was added
and subsequently evaporated at reduced pressure. This
procedure was repeated three times. The resulting oil
was dissolved in HCl-saturated methanol followed by
slow addition of HCl-saturated diethyl ether causing
precipitation of the hydrochloride to occur. The white
precipitate was filtered off, washed with ether and dried
at reduced pressure over NaOH pellets. Recrystallisa-
tion from methanol gave white needle-like crystals
(1.91 g, 73%), mp 183–184 ꢁC. (Found C, 33.08; H,
7.89; N, 19.06. C6H17Cl2N3O requires C, 33.04; H,
7.86; N, 19.26%); mmax (KBr)/cmꢂ1 3500–2200vs
(mNH3+), 3252vs (mNH), 1969m, 1679vs (mCO); dH
(DMSO-d6) 1.46 (2H, m, CH2), 1.59 (2H, m, CH2),
2.74 (2H, m, CH2), 3.10 (2H, m, CH2), 3.51 (2H, s,
N–CH2–CO), 8.21 (3H, s, NH3+), 8.29 (3H, s, NH3+),
8.70 (1H, t, J(H,H) = 5.7 Hz, NH); dC (DMSO-d6)
24.3, 25.8, 38.0, 38.3, 40.1, 165.8; m/z (FAB) 146
([M+H]+).
4.8.17. Boc-glycine. Boc-glycine was prepared from gly-
cine and di-tert-butyldicarbonate essentially by the pro-
cedure described,79 scaled to 1:10. Recrystallisation
yielded pure white crystals (89%), mp 87–88 ꢁC. The
presence of both the E- and Z-isomers of the amide is
observed (1H and 13C NMR). (Found: C, 47.91;
H, 7.55; N, 8.08. C7H13NO4 requires C, 47.99; H,
7.48; N, 8.00%); mmax (KBr)/cmꢂ1 3500–2400s (mCOOH),
3407m, 3343s (dNH), 1749vs (mCOOH), 1668vs
(mCONH), 1541vs (dNH), 1411s, 1369m, 1215vs,
1198vs, 1058m, 959m, 860m; dH (CDCl3) 1.43 (9H, s,
CH3), 3.86 and 3.93 (2H, s, CH2), 5.23 and 6.65 (1H,
s, NH), 10.05 (1H, s, COOH); dC (CDCl3) 28.1, 42.1
and 43.2, 80.3 and 81.7, 155.9 and 157.1, 173.8 and
174.4; m/z (EI) 160 (2%, MꢂCH3), 130 (11, MꢂCOOH),
120 (60), 116 (4, MꢂCH2COOH), 102 (5,
MꢂOC(CH3)3), 76 (21), 59 (90, Mꢂ(CH3)3COCONH),
57 (100, MꢂO2CNCH2COOH), 41 (40), 29 (24).
4.8.18. Boc-putrescine. Using the previously described
procedure80 Boc-putrescine was prepared from putres-
cine and di-tert-butyldicarbonate (83%). The colourless
oilwas shown to be pure by GC–MS but too hygroscopic
for elemental analysis. mmax (KBr)/cmꢂ1 3363vs, 2934vs,
2175w, 1688vs, 1525vs, 1365s, 1173vs, 1042m, 993m,
868m; dH (CDCl3) 1.3–1.5 (13H, m, CH3+2 · CH2),
2.07 (2H, s, NH2), 2.64 (2H, t, J(H,H) = 6.6 Hz, N–
CH2), 3.03 (2H, t, J(H,H) = 6.6 Hz, N–CH2), 4.88 (1H,
s, NH); dC (CDCl3) 27.3, 28.2, 30.1, 40.2, 41.3, 78.7,
155.9; m/z (EI) 188 (0.1%, M+), 143 (2), 132 (28), 115
(22, MꢂOC(CH3)3), 114 (19), 103 (19), 98 (17), 74 (33),
70 (64), 57 (79, (CH3)3C), 59 (58), 41 (45), 30 (100,
CH2@NH2).
4.8.21. N-(2-Aminoethyl)-putrescine trihydrochloride. A
suspension of N-(2-aminoacetyl)-putrescine dihydro-
chloride (1.45 g, 6.6 mmol) in dry THF (135 mL) was
added slowly to a stirred solution of borane–THF com-
plex (1.0 M, 75 mL, 75 mmol) under nitrogen. The reac-
tion mixture was refluxed for 48 h and cooled to room
temperature, whereupon it was quenched by slow addi-
tion of methanol (180 mL) followed by reflux overnight.