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using Method E: for (S)-16b, [a]D+15.4ꢀ (c 1.8, CHCl3);
1H NMR (CDCl3) d 1.22±1.24 (d, 3H), 1.72±1.79 (m,
2H), 2.28±2.36 (m, 4H), 3.75 (t, 2H), 3.88±3.94 (m, 1H).
(Spectra identical for 16b and (S)-16b).
1,7-Diaminonon-3-yne dihydrochloride (19c). From 18c
1
by Method H: H NMR (D2O) d 0.99 (t, 3H), 1.71±1.81
(m, 2H), 1.83±1.93 (m, 2H), 2.36 (t, 2H), 2.53±2.70 (m,
2H), 3.11 (t, 2H), 3.32±3.38 (m, 1H); MS (FAB, t-glyc)
155 (M+H).
Non-4-yn-1,7-diol (16c). Prepared from 15c in 77% yield
using Method E and ¯ash chromatographed in 1/1,
acetone/hexane for puri®cation: 1H NMR (CDCl3) d
0.95 (t, 3H), 1.50±1.60 (m, 2H), 1.73±1.80 (m, 2H), 2.28±
2.34 (m, 2H), 2.38±2.44 (m, 2H), 3.61±3.65 (m, 1H), 3.76
(t, 2H).
1,7-Diamino-trans-hept-3-ene dihydrochloride (20a). From
19a (free base) by Method I: 1H NMR (D2O) d 1.71±1.81
(m, 2H), 2.12±2.19 (m, 2H), 2.36±2.43 (m, 2H), 2.98±3.08
(m, 4H), 5.49±5.56 (m, 1H), 5.64±5.71 (m, 1H); MS
(FAB, t-glyc) 129 (M+H).
Hept-3-yn-1,7-dimesylate (17a). Obtained as an oil
1
1,7-Diamino-trans-oct-3-ene dihydrochloride (20b). Method
M. To a solution of racemic 19b (free base, 0.28 g,
2 mmol) in 8 mL of diglyme was added slowly with stir-
ring under argon LiAlH4 (0.5 M in diglyme, 13 mL,
6.5 mmol). The mixture was heated at re¯ux for 18 h,
cooled and hydrolyzed carefully with water using exter-
nal cooling. After ®ltration with the use of celite, the
solvent was removed under high vacuum. The residue
was dissolved in 10 mL of water, basi®ed (solid NaOH)
and extracted with methylene chloride (5Â20 mL).
Satisfactorily puri®ed product could not be obtained by
¯ash chromatography. Therefore the material was
chromatographed by the ion exchange procedure
described in Method C. Compound 20b emerged from
the column between 50 and 75 mL and was obtained as a
(97%) from 16a using Method F: H NMR (CDCl3) d
1.90±1.95 (m, 2H), 2.32±2.36 (m, 2H), 2.61±2.67 (m,
2H), 3.04 (s, 3H), 3.06 (s, 3H), 4.27 (t, 2H), 4.35 (t, 2H).
Oct-3-yn-1,7-dimesylate (17b and (S)-17b). By Method F
from 16b and (S)-16b (98% and 100%, respectively): 1H
NMR (CDCl3) d 1.46±1.49 (d, 3H), 1.88±1.96 (m, 2H),
2.34 (t, 2H), 2.54±2.56 (m, 2H), 3.03 (s, 3H), 3.04 (s,
3H), 4.34 (t, 2H), 4.81±4.86 (m, 1H). (Spectra identical
for 17b and (S)-17b).
Non-3-yn-1,7-dimesylate (17c). By Method F from 16c
1
(99%): H NMR (CDCl3) d 1.01 (t, 3H), 1.77±1.85 (m,
2H), 1.89±1.97 (m, 2H), 2.32±2.34 (m, 2H), 2.59±2.62 (m,
2H), 3.03 (s, 3H), 3.06 (s, 3H), 4.35 (t, 2H), 4.65±4.69
(m, 1H).
1
colorless oil (0.085 g, 24%) upon removal of solvent: H
NMR (D2O) d 1.28±1.31(d, 3H), 1.71±1.81 (m, 2H),
2.13±2.20 (m, 2H), 2.33±2.38 (m, 2H), 3.00 (t, 2H), 3.37±
3.44 (m, 1H), 5.48±5.57 (m, 1H), 5.64±5.74 (m, 1H); MS
(FAB, t-glyc) 143 (M+H).
Hept-3-yn-1,7-diazide (18a). From 17a using Method G
(70%): 1H NMR (CDCl3) d 1.71±1.81 (m, 2H), 2.26±
2.33 (m, 2H), 2.43±2.50 (m, 2H), 3.34±3.44 (t, 4H).
1,7-Diamino-cis-hept-3-ene dihydrochloride (21a). From
19a free base by Method J: 1H NMR (D2O) d 1.71±1.81
(m, 2H), 2.16±2.23 (m, 2H), 2.43±2.50 (m, 2H), 2.99±
3.08 (m, 4H), 5.46±5.51 (m, 1H), 5.63±5.71 (m, 1H); MS
(FAB, t-glyc) 129 (M+H).
Oct-3-yn-1,7-diazide (18b and (S)-18b). By Method G
1
from 17b and (S)-17b (65% and 70%, respectively): H
NMR (CDCl3) d 1.31±1.33 (d, 3H), 1.72±1.81 (m, 2H),
2.31±2.33 (m, 2H), 2.36±2.39 (m, 2H), 3.41 (t, 2H), 3.57-
3.63 (m, 1H). (Spectra identical for 18b and (S)-18b).
1,7-Diamino-cis-oct-3-ene dihydrochloride (21b). From
1
Non-3-yn-1,7-diazide (18c). By Method G from 17c
1
racemic 19b free base by Method J: H NMR (D2O) d
(52%): H NMR (CDCl3) d 1.00 (t, 3H), 1.56±1.71 (m,
2H), 1.73±1.81 (m, 2H), 2.28±2.33 (m, 2H), 2.40±2.43
(m, 2H), 3.34±3.38 (m, 1H), 3.42 (t, 2H).
1.30±1.32 (d, 3H), 1.71±1.81 (m, 2H), 2.16±2.23 (m, 2H),
2.39±2.45 (m, 2H), 3.01 (t, 2H), 3.39±3.46 (m, 1H), 5.45±
5.54 (m, 1H), 5.65±5.73 (m, 1H); MS (FAB, t-glyc) 143
(M+H).
1,7-Diaminohept-3-yne dihydrochloride (19a). From 18a
1
using Method H: H NMR (D2O) d 1.85±1.90 (m, 2H),
2.35 (t, 2H), 2.61 (t, 2H), 3.09±3.17 (m, 4H); MS (FAB,
t-glyc) 127 (M+H).
1,7-Diguanidinohept-3-yne sulfate (22a). From 19a by
Method K: 1H NMR (D2O) d 1.75±1.82 (m, 2H), 2.29 (t,
2H), 2.48 (t, 2H), 3.27±3.36 (m, 4H); MS (FAB, t-glyc)
211 (M+H), 309 (M+H+H2SO4).
1,7-Diaminooct-3-yne dihydrochloride (19b and (S)-19b).
1
From 18b and (S)-18b by Method H: H NMR (D2O) d
1,7-Diguanidinooct-3-yne dihydrochloride (22b and (S)-
22b). Method N. To solutions of 19b and (S)-19b (free
bases, 0.14 g, 1 mmol) in 1 mL of DMF were added 1H-
pyrazole-1-carboxamidine.HCl (0.31 g, 2.1 mmol) and
diisopropylethylamine (0.383 mL, 2.2 mmol) under
1.36±1.38 (d, 3H), 1.84±1.93 (m, 2H), 2.35±2.40 (m, 2H),
2.50±2.67 (m, 2H), 3.12 (t, 2H), 3.50±3.57 (m, 1H); MS
(FAB, t-glyc) 141 (M+H). (Spectra identical for 19b
and (S)-19b).