PAPER
Synthesis of Macrocyclic Teteraamides and Related Compounds
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1H NMR (CDCl3): = 0.89 (t, J = 6.9 Hz, 6 H, CH3), 2.42 (q, J = 7
Hz, 4 H, CH2CH3), 2.97 (s, 2 H, COCH2N), 3.75 (m, 4 H, CH2NH),
3.96 (d, J = 5.8 Hz, 4 H, OCH2), 4.78 (d, J = 15.3 Hz, 2 H, upfield
of OCH2CO), 4.94 (d, J = 15.3 Hz, 2 H, downfield of OCH2CO),
5.45 (quintet, J = 5.5 Hz, 1 H, CHO), 6.62–8.89 (m, 20 H, ArH +
NH).
of OCH2CH2N and 2 H of NCH2), 3.70–3.85 (m, 2 H, NCH2), 3.86–
4.00 (m, 4 H, OCH2), 4.84 (d, J = 15.3 Hz, 2 H, downfield of
OCH2CO), 4.99 (d, J = 15 Hz, 2 H, upfield of OCH2CO), 5.34
(quintet, J = 5.7 Hz, 1 H, CHO), 6.71–8.27 (m, 16 H, ArH), 8.20 (t,
J = 6 Hz, 2 H, CONHCH2), 8.98 (s, 2 H, CH2CONH).
MS: m/z (%) = 795 (M+, 11), 777 (23), 584 (17), 337 (25), 186
MS: m/z (%) = 768 (M + 1, 0.5), 665 (0.5), 521 (1), 413 (2.1), 326
(100), 113 (88).
(2), 300 (10), 140 (32), 85 (100).
Anal. Calcd for C42H45N5O11 (795.85): C, 63.39; H, 5.70; N, 8.80.
Found: C, 63.45; H, 5.55; N, 8.70.
Anal. Calcd for C41H45N5O10 (767.83): C, 64.14; H, 5.91; N, 9.12.
Found: C, 64.34; H, 5.99; N, 9.24.
1,4-Bis{6,14,15,24,32,33-hexahydro-16H-tetrabenzo[b,h,p,v]-
[1,7,18,24,4,11,14,21]tetraoxatetraazacycloheptacosin-
7,23,30,35-(8H,22H,31H,34H)tetraone-15-yloxycarbonylmeth-
yl}piperazine (21)
By the general procedure 19a and piperazine gave crude 21, which
was crystallized from dioxane to give pale yellow crystals (50%);
mp 248–250 °C.
15-Morpholinoacetoxy-6,14,15,24,32,33-hexahydro-16H-tetra-
benzo[b,h,p,v][1,7,18,24,4,11,14,21]tetraoxatetraazacyclohepta-
cosin-7,23,30,35-(8H,22H,31H,34H)tetraone (20b)
By the general procedure 19a and morpholine gave crude 20b,
which was crystallized from MeOH to give colorless crystals
(65%); mp 184–186 °C.
IR (KBr): 3384, 3335 (NH), 1729, 1692, 1636 cm–1 (C=O).
IR (KBr): 3392, 3325 (NH), 1760, 1693, 1635 cm–1 (C=O).
1H NMR (CDCl3): = 2.33 (t, J = 4.5 Hz, 4 H, NCH2CH2O), 2.84
(s, 2 H, COCH2N), 3.58 (t, J = 4.5 Hz, 4 H, OCH2CH2N), 3.74 (br
s, 4 H, CH2NHCO), 3.95 (d, J = 5.7 Hz, 4 H, OCH2), 4.73 (d, J = 15
Hz, 2 H, upfield of OCH2CO), 4.92 (d, J = 15 Hz, 2 H, downfield of
OCH2CO), 5.38 (quintet, J = 5.7 Hz, 1 H, CHO), 6.73–8.26 (m, 16
H, ArH), 8.33 (br s, 2 H, CONHCH2), 8.85 (s, 2 H, CH2CONH).
13C NMR (APT pulse sequence, CDCl3): = 41.12, 53.03, 58.9,
66.54, 66.87, 68.85, 122.29, 126.69, 145.35, 147.08, 155.41, 165.9,
166.09 (C and CH2), 70.05, 111.42, 112.4, 121.12, 121.82, 122.29,
124.66, 131.84, 132.77 (CH).
1H NMR (DMSO-d6): = 2.22 (br s, 8 H, CH2N), 2.99 (br s, 4 H,
COCH2N), 3.51 (br s, 8 H, CH2NHCO), 4.31 (br s, 8 H, OCH2), 4.33
(s, 8 H, OCH2CO), 5.55 (br s, 2 H, OCH), 6.94–7.89 (m, 32 H,
ArH), 8.71 (br s, 4 H, CONHCH2), 9.39 (s, 4 H, CH2CONH).
13C NMR (DMSO-d6):
= 51.46, 57.96, 67.42, 67.84, 69.85,
113.09, 113.36, 120.96, 121.33, 122.20, 124.17, 125.02, 126.59,
130.04, 131.82, 148.71, 154.94, 165.49, 166.29, 169.20.
Anal. Calcd for C78H78N10O20 (1475.53): C, 63.49; H, 5.33; N, 9.49.
Found: C, 63.33; H, 5.29; N, 9.52.
MS: m/z (%) = 780 (M – 1, 7.1), 715 (7), 604 (13), 552 (17.2), 423
(15.4), 333 (11), 281 (23), 262 (100), 183 (24).
References
Anal. Calcd for C41H43N5O11 (781.82): C, 62.99; H, 5.54; N, 8.96.
Found: C, 63.05; H, 5.50; N, 8.72.
(1) Irie, S.; Yamamoto, M.; Kishikawa, K.; Kohmoto, S.;
Yamada, K. Synthesis 1995, 1179.
(2) Fujita, T.; Lehn, J. M. Tetrahedron Lett. 1988, 29, 1122.
(3) Cram, D. J. Angew. Chem., Int. Ed. Engl. 1986, 25, 1035.
(4) Grammenudi, S.; Vögtle, F. Angew. Chem., Int. Ed. Engl.
1986, 25, 1122.
(5) Pioget, T.; Duriez, M. C.; Picard, C.; Cazaux, L.; Tisnes, P.
Tetrahedron 1992, 48, 4359.
(6) Cazaux, L.; Duriez, M. C.; Picard, C.; Tisnes, P.
Tetrahedron Lett. 1989, 30, 1369.
(7) Cazaux, L.; Picard, C.; Pigot, T.; Tisnes, P. Tetrahedron
Lett. 1991, 32, 919.
(8) Nakatsuji, Y.; Kobayashi, H.; Okahara, M.; Matsushima, K.
Chem. Lett. 1982, 1571.
(9) Maruizumi, T.; Wegmann, D.; Suter, G.; Ammann, D.;
Simon, W. Mikrochim. Acta 1986, 63, 2271.
(10) Kataky, R.; Nicholson, P. E.; Paeker, D.; Covington, A. K.
The Analyst 1991, 116, 135.
(11) Erne, D.; Stojanac, N.; Ammann, D.; Hofstetter, P.; Pretsch,
E.; Simon, W. Helv. Chim. acta 1980, 63, 2271.
(12) Schefer, U.; Ammann, D.; Pretsch, E.; Oesch, U.; Simon, W.
Anal. Chem. 1986, 58, 2282.
15-Piperidinoacetoxy-6,14,15,24,32,33-hexahydro-16H,34H-
tetrabenzo[b,h,q,w][1,7,19,25,4,11,15,22]tetraoxatetraazacy-
clooctacosin-7,23,30,36-(8H,22H,31H,35H)tetraone (20c)
By the general procedure 19b and piperidine gave crude 20c, which
was crystallized from EtOH to give colorless crystals (60%); mp
192–194 °C.
1H NMR (CDCl3): = 1.25–1.34 (m, 2 H, CH2CH2CH2N), 1.40–
1.49 (m, 4 H, CH2CH2CH2N), 1.9 (br s, 2 H, NCH2CH2CH2N), 2.23
(t, J = 4.8 Hz, 4 H, NCH2CH2CH2), 2.85 (s, 2 H, COCH2N), 3.49–
3.60 (m, 2 H, NCH2), 3.70–3.79 (m, 2 H, NCH2), 3.87–4.0 (m, 4 H,
OCH2), 4.82 (d, J = 15.3 Hz, 2 H, downfield of OCH2CO), 4.97 (d,
J = 15.3 Hz, 2 H, upfield of OCH2CO), 5.36 (quintet, J = 5.4 Hz, 1
H, CHO), 6.71–8.25 (m, 18 H, ArH and CONHCH2), 8.99 (s, 2 H,
CH2CONH).
13C NMR (CDCl3): = 23.23, 25.69, 30.09, 36.27, 54.03, 59.57,
67.01, 69.39, 69.75, 111.34, 112.64, 121.52, 121.73, 122.30,
122.77, 124.82, 126.65, 132.04, 132.66, 147.39, 155.41, 165.61,
166.19, 169.72.
(13) Collins, T. J.; Kostka, K. L.; Munck, E.; Uffelman, E. S. J.
Am. Chem. Soc. 1990, 112, 5637.
Anal. Calcd for C43H47N5O10 (793.87): C, 65.06; H, 5.97; N, 8.82.
Found: C, 64.90; H, 5.67; N, 8.75.
(14) Kimura, E. Pure Appl. Chem. 1989, 61, 823.
(15) Kimura, E.; Kurogi, Y.; Wada, S.; Shionoya, M. J. Chem.
Soc., Chem. Commun. 1989, 781.
(16) Gordon, W.; Scott, W.; Collins, T. J. US Patent 6051704,
2000; Chem. Abstr. 2000, 132, 273412.
15-Morpholinoacetoxy-6,14,15,24,32,33-hexahydro-16H,34H-
tetrabenzo[b,h,q,w][1,7,19,25,4,11,15,22]tetraoxatetraazacy-
clooctacosin-7,23,30,36-(8H,22H,31H,35H)tetraone (20d)
By the general procedure 19b and morpholine gave crude 19b,
which was crystallized from EtOH to give colorless crystals (65%);
mp 217–219 °C.
(17) Kumar, S.; Hundal, M. S.; Hundal, G.; Kaur, N.; Singh, H.
Tetrahedron 1997, 53, 10841.
(18) Kumar, S.; Hundal, G.; Kaur, N.; Hundal, M. S.; Singh, H.
Tetrahedron Lett. 1997, 38, 131.
(19) Krakowiak, K. E.; Bradshaw, J. S.; Zamecka-Krakowiak, D.
J. Chem. Rev. 1989, 89, 929.
IR (KBr): 3389, 3335 (NH), 1769, 1697 cm–1 (C=O).
1H NMR (CDCl3): = 1.83 (m, 2 H, CH2CH2N), 2.30 (t, J = 4.5 Hz,
4 H, NCH2CH2O), 2.84 (s, 2 H, COCH2N), 3.50–3.58 (m, 6 H, 4 H
Synthesis 2004, No. 3, 419–428 © Thieme Stuttgart · New York