Syntheses of (-)-(7S)- and (+)-(7R)-K252a dimers

Article abstract of DOI:10.1016/S0040-4039(01)02166-9

This letter describes syntheses of (-)-(7S)-and (+)-(7R)-K252a dimers wherein a convergent bis-indole-N-glycosidic coupling step was used for the resolution of the C(7) substituted (±)-aglycon. Dimerization of the derived monomers was achieved via olefin methathesis.

Full text of DOI:10.1016/S0040-4039(01)02166-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 43 (2002) 379–382
Syntheses of (−)-(7S)- and (+)-(7R)-K252a dimers
Kazuhiko Tamaki, Elliott W. D. Huntsman, Dejah T. Petsch and John L. Wood*
Sterling Chemistry Laboratories, Department of Chemistry, Yale University, New Haven, CT 06520-8107, USA
Received 7 August 2001; revised 8 November 2001; accepted 13 November 2001
Abstract—This letter describes syntheses of (−)-(7S)-and (+)-(7R)-K252a dimers wherein a convergent bis-indole-N-glycosidic
coupling step was used for the resolution of the C(7) substituted ( )-aglycon. Dimerization of the derived monomers was achieved
via olefin methathesis. © 2002 Elsevier Science Ltd. All rights reserved.
K252a (1) (Fig. 1),1 isolated originally from the culture
broth of Actinomadura by Sezaki and then reisolated
from Nocardiopsis by Kase in a screen for antagonists
of Ca2+ mediated signaling, has been implicated in the
inhibition of several tyrosine kinases (Trks) and has
been shown to be a potent PKC inhibitor.2 Trk medi-
ated PDGF signal transduction is potentially a novel
therapeutic inroad for the treatment of human gliomas
and follows the general motif of receptor tyrosine
kinases (i.e. dimerization and autophosphorylation).3
Based on recent work demonstrating that dimeric natu-
ral product probes function particularly efficiently as
tools for chemical biology,4–6 we became curious as to
whether multivalent analogs of K252a would have a
selective influence on receptor-type kinases. Thus, we
initiated an effort to prepare K252a analogs poised for
subsequent conversion to dimeric or higher valent spe-
cies. Recently, efforts to access novel K252a analogs
have resulted in a convergent route to C7 and C2%
alkylated K252a analogs.7a–d Herein, we describe a
synthesis of (−)-(7S)-and (+)-(7R)-K252a dimers (2 and
3) utilizing olefin methathesis. The requisite monomers
were prepared using an expansion of our strategy for
the construction of C7 alkylated K252a analogs.7b,c
The synthesis of ( )-aglycon 11 is outlined in Scheme 1.
Thus, alkylation of known imine 4 with 8-bromo-1-
octene according to O’Donnel’s procedure followed by
hydrolysis of the imine afforded ethyl 2-amino-9-
decenoate hydrochloride (5) in 72% overall yield.8 A
two-step reductive amination utilizing 3,4-dimethoxy-
benzaldehyde and NaBH4 gave DMB (3,4-dimethoxy-
benzyl) protected amine 6 in 81% yield. Acylation with
ethyl hydrogen malonate under standard coupling con-
ditions (DCC/DMAP) afforded 7 in 92% yield. Dieck-
mann cyclization (NaOEt/EtOH) followed by
decarboalkoxylation in wet CH3CN gave N-DMB-pro-
tected tetramic acid 8 (84%, two steps). Subsequent
diazotransfer with 4-nitrobenzenesulfonyl azide in the
presence of Et3N smoothly gave diazolactam 9 in 93%
yield.9 According to previous protocols, 9 and biindole
10 were treated with Rh2(OAc)4 in degassed pinacolone
under reflux for 8 h. Successive C–H insertion, electro-
cyclization and aromatization gave the desired N-DMB
H
N
7
H
H
N
O
N
O
O
7
7
8
4
8
N
N
N
N
N
N
O
11
O
O
1
1'
2'
MeO2C
CO2Me
MeO2C
OH
HO
OH
(-)-(7S)-K252a dimer (2)
(+)-(7R)-K252a dimer (3)
K252a (1)
Figure 1.
* Corresponding author. Fax: 203-432-6104; e-mail: john.wood@yale.edu
0040-4039/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)02166-9

380
K. Tamaki et al. / Tetrahedron Letters 43 (2002) 379–382
O
O
1) 8-bromo-1-octene
K2CO3, nBu4NBr
CH3CN, reflux
1) 3,4-dimethoxy-
benzaldehyde
Et3N, EtOH
HO
OEt
6
6
OEt
DCC, DMAP
OEt
OEt
H2N
HCl
DMB N
H
N
2) 1N HCl, Et2O
(72%, 2 steps)
2) NaBH4, EtOH
(81%, 2 steps)
O
CH2Cl2
(92%)
O
O
5
4
6
N
H
N
4-nitrobenzene-
sulfonyl azide
H
10
DMB
N
DMB
N
1) NaOEt, EtOH
reflux
Rh2(OAc)4
6
Et3N
O
O
OEt
DMB N
O
6
6
degassed pinacolone
reflux, (33%)
(57%based
2) CH3CN-H2O
reflux
(84%, 2 steps)
CH3CN
(93%)
O
N2
O
O
8
7
9
on recovered 10 )
O
OEt
DMB
DMB
N
DMB
N
N
O
O
O
6
6
6
DMB
N
O
12a-12d
CSA (0.1eq)
+
+
6
N
N
N
N
N
N
11
11
11
O
O
1
O
1
1
1,2-dichloroethane
reflux, 72 hr
MeO2C
MeO2C
MeO2C
N
H
N
OH
OH
(+)-14 (19%)
OH
H
(±)-11
(+)-15 (10%)
(-)-16 (9%)
(-)-13 (20%)
O
O
MeO
OMe MeO
OMe
+
O
O
OMe
OMe
+
HO
MeO2C
MeO2C
OH
OH
OMe
12a-12d
Scheme 1.
protected aglycon ( )-11 in 33% yield (57% based on
recovered 10).7a With 11 in hand we explored the
one-step acid catalyzed bis-indole-N-glycosidic cou-
pling with enantioenriched 12a–12d.7a,10 Slow addition
(24 h) of 12a–12d (a solution in 1,2–dichloroethane) to
11 and CSA (0.1 equiv.) in 1,2-dichloroethane followed
by an additional 48 h at reflux gave a 2:2:1:1
diastereomeric mixture of methathesis precursors (13–
16). Following isolation of the individual diastereomers
by careful preparative TLC,11–14 the initial regiochemi-
chemistry to the major regioisomers (−)-13 and (+)-14
was made by comparison to previously prepared C7-
methyl-6-N-DMB-K252a7b,c and C7-benzyl-6-N-DMB-
K252a7c analogs. The relative stereochemistry of (+)-15
and (−)-16 remains ambiguous due to a lack of com-
parison data.
Treatment of (−)-13 with Grubbs’ catalyst (Scheme 2)15
(8 mol%) at room temperature in CH2Cl2 for 43 h gave
the desired dimer as a mixture of E and Z isomers.16
Subsequent hydrogenation with 5% Rh/Al2O3 afforded
(7S)-6-N-DMB-dimer 17 in 87% overall yield. Final
1
cal assignment for 13–16 was made based on H NMR
analysis. Subsequent assignment of the relative stereo-
DMB
DMB
N
H
N
H
N
O
N
O
O
O
8
8
1) Grubbs' catalyst
CH2Cl2
TFA
anisole
3)
(-)-13
N
N
N
N
N
N
N
N
O
O
2) 5% Rh-Al2O3 , H2
THF - EtOH
(87%, 2 steps)
O
O
CH2Cl2
(50%)
17
2
CO2Me
MeO2C
CO2Me
MeO2C
HO
OH
HO
OH
H
N
H
N
O
O
8
1) - 3)
(+)-14
N
N
N
N
(49%, 3 steps)
O
O
3
CO2Me
MeO2C
HO
OH
Scheme 2.

K. Tamaki et al. / Tetrahedron Letters 43 (2002) 379–382
381
DMB deprotection was carried out with TFA in the
presence of anisole to provide the (−)-(7S)-K252a dimer
(2) in 50% yield.17 An identical reaction sequence utiliz-
ing (+)-14 furnished the corresponding (+)-(7R)-K252a
dimer (3) in 49% overall yield.18
University, 1999; (d) Tamaki, K.; Shotwell, J. B.; White,
R. D.; Drutu, I.; Petsch, D. T.; Nheu, T. V.; He, H.;
Hirokawa, Y.; Maruta, H.; Wood, J. L. Org. Lett. 2001,
3, 1689–1692.
8. O’Donnell, M. J.; Wojciechowski, K.; Ghosez, L.;
Navarro, M.; Sainte, F.; Antoine, J.-P. Synthesis 1984,
313–315.
9. Rector, D. L.; Harmon, R. E. J. Org. Chem. 1966, 31,
2837–2841.
10. The four diasteromers (12a–12d) were all derived from
alcohol 18 (92% ee) and lead to identical cyclofulanosyla-
tion products. See Ref. 7a.
In conclusion, the first total synthesis of a C7 linked
dimer of K252a has been completed. The synthesis
expands the scope of our aglycon synthesis and estab-
lishes the feasibility of using cyclofuranosylation with
enentioenriched carbohydrate precursors as a means to
resolve racemic aglycons. Evaluation of the biological
activity of these dimers is underway and has already
established them to be potent kinase inhibitors.
O
O
O
O
MeO
OMe MeO
OMe
+
ref. 7a
O
O
OMe
OMe
OMe
+
HO
HO
MeO2C
MeO2C
OH
OH
OMe
18 (92% ee)
12a-12d
Acknowledgements
11. (−)-(7S)-(1-Octenyl)-N-DMB-K252a (13): a pale yellow
powder; [h]2D0 −36.0 (c 0.30, CHCl3); IR (thin film/NaCl)
3298 (br w), 2930 (m), 2854 (w), 1733 (m), 1673 (s), 1646
We acknowledge the support of this work by Bristol–
Myers Squibb, Eli Lilly, Glaxo–Wellcome, Merck,
Pfizer, Yamanouchi, and Zeneca through their Faculty
Awards Programs and the Camille and Henry Dreyfus
Foundation for a Teacher–Scholar Award. J.L.W. is a
fellow of the Alfred P. Sloan Foundation. K.T. thanks
Sankyo Co., Ltd. for research support and J. Brad
Shotwell for helpful comments during the preparation
of the manuscript.
(s), 1585 (m), 1515 (m), 1459 (s), 1392 (m) cm−1 1H
;
NMR (400 MHz, acetone-d6): l 9.51 (d, J=7.9 Hz, 1H),
8.09 (d, J=7.3 Hz, 1H), 8.00 (d, J=8.2 Hz, 1H), 7.81 (d,
J=8.1 Hz, 1H), 7.51 (app t, J=7.8 Hz, 1H), 7.43 (app t,
J=7.8 Hz, 1H), 7.36–7.26 (m, 2H), 7.17 (dd, J=5.0, 7.6
Hz, 1H), 7.11 (d, J=1.8 Hz, 1H), 7.01 (dd, J=1.8, 8.3
Hz, 1H), 6.92 (d, J=8.3 Hz, 1H), 5.60 (ddt, J=10.2,
17.0, 6.8 Hz, 1H), 5.34 (app t, J=3.2 Hz, 1H), 5.34 (d,
J=15.1 Hz, 1H), 5.27 (s, 1H), 4.80 (m, 1H), 4.76 (m, 1H),
4.42 (d, J=15.1 Hz, 1H), 4.01 (s, 3H), 3.77 (s, 3H), 3.76
(s, 3H), 3.49 (dd, J=7.6, 14.2 Hz, 1H), 2.52 (m, 1H), 2.41
(m, 1H), 2.23 (s, 3H), 2.20 (m, 1H), 1.82–1.73 (m, 2H),
1.12–0.92 (m, 7H), 0.54 (m, 1H); 13C NMR (100 MHz,
CDCl3): l 173.8, 169.8, 149.0, 148.2, 140.3, 138.9, 137.0,
134.2, 130.4, 128.9, 126.4, 125.6, 125.0, 124.5, 124.0,
122.6, 121.9, 120.6, 120.1, 119.6, 119.3, 116.7, 114.8,
114.2, 113.9, 111.0, 110.7, 107.3, 98.9, 85.3, 84.7, 60.0,
55.8, 55.8, 53.7, 43.6, 42.2, 33.5, 29.2, 29.0, 28.6, 28.5,
22.8, 21.6; HRMS (FAB) m/z 728.3339 [calcd for
C44H46N3O7 (M+H) 728.3336].
References
1. Sezaki, M.; Sasaki, T.; Nakazawa, T.; Takeda, U.; Iwata,
M.; Watanabe, T.; Koyama, M.; Kai, F.; Shomura, T.;
Kojima, M. J. Antibiot. 1985, 38, 1437–1439.
2. (a) Kase, H.; Iwahashi, K.; Matsuda, Y. J. Antibiot.
1986, 39, 1059–1065; (b) Nakanishi, S.; Matsuda, Y.;
Iwahashi, K.; Kase, H. J. Antibiot. 1986, 39, 1066–1071;
(c) Yasuzawa, T.; Iida, T.; Yoshida, M.; Hirayama, N.;
Takahashi, M.; Shirahata, K.; Sano, H. J. Antibiot. 1986,
39, 1072–1078.
12. (+)-(7R)-(1-Octenyl)-N-DMB-K252a (14): a pale yellow
powder; [h]2D0 +74.8 (c 0.21, CHCl3); IR (thin film/NaCl)
3485 (br w), 3304 (br w), 3069 (w), 2998 (m), 2928 (s),
2854 (m), 1732 (s), 1673 (s), 1585 (m), 1515 (s), 1452 (s),
3. Chin, L. S.; Murray, S. F.; Zitnay, K. M.; Rami, B. Clin.
Cancer. Res 1997, 3, 771–776.
4. Indeed, several dimeric natural product-like inhibitors
have been designed and synthesized, including FK5064,
cyclosporin A5, and 1a,25-dihydroxyvitamin D3;6 (a)
Spencer, D. M.; Wandless, T. J.; Schreiber, S. L.; Crab-
tree, G. R. Science 1993, 262, 1019–1024; (b) Pruschy, M.
N.; Spencer, D. M.; Kapoor, T. M.; Miyake, H.; Crab-
tree, G. R.; Schreiber, S. L. Chem. Biol. 1994, 1, 163–172;
(c) Diver, S. T.; Schreiber, S. L. J. Am. Chem. Soc. 1997,
119, 5106–5109.
1392 (s) cm−1 1H NMR (400 MHz, acetone-d6): l 9.51
;
(d, J=7.8 Hz, 1H), 8.12 (d, J=7.6 Hz, 1H), 8.01 (d,
J=8.5 Hz, 1H), 7.80 (d, J=8.3 Hz, 1H), 7.51 (app t,
J=7.4 Hz, 1H), 7.43 (app t, J=7.5 Hz, 1H), 7.36–7.27
(m, 2H), 7.15 (dd, J=5.1, 7.3 Hz, 1H), 7.12 (d, J=1.8
Hz, 1H), 7.02 (dd, J=1.8, 8.2 Hz, 1H), 6.93 (d, J=8.2
Hz, 1H), 5.61 (ddt, J=10.3, 17.1, 6.8 Hz, 1H), 5.39 (s,
1H), 5.36 (m, 1H), 5.34 (d, J=15.2 Hz, 1H), 4.81 (m,
1H), 4.76 (m, 1H), 4.42 (d, J=15.2 Hz, 1H), 4.02 (s, 3H),
3.78 (s, 3H), 3.77 (s, 3H), 3.51 (dd, J=7.3, 14.2 Hz, 1H),
2.54–2.35 (m, 2H), 2.36 (dd, J=5.1, 14.2 Hz, 1H), 2.18 (s,
3H), 1.82–1.75 (m, 2H), 1.12–0.83 (m, 7H), 0.50 (m, 1H);
13C NMR (100 MHz, CDCl3): l 174.2, 169.8, 149.2,
148.3, 140.1, 139.0, 137.2, 134.7, 130.3, 128.8, 126.9,
125.8, 125.0, 124.4, 124.3, 123.3, 122.4, 120.6, 120.3,
120.2, 117.1, 114.9, 114.0, 113.9, 111.0, 111.0, 107.3, 98.5,
85.0, 84.3, 58.7, 55.9, 55.8, 54.2, 43.6, 41.5, 33.6, 29.2,
29.1, 28.8, 28.6, 22.8, 21.6; HRMS (FAB) m/z 728.3339
[calcd for C44H46N3O7 (M+H) 728.3336].
5. Belshaw, P. J.; Spencer, D. M.; Crabtree, G. R.;
Schreiber, S. L. Chem. Biol. 1996, 3, 731–738.
6. Sestelo, J. P.; Mourin˜o, A.; Sarandeses, L. A. J. Org.
Chem. 2000, 65, 8290–8296.
7. In this study, the choices of linker length and position of
attachment (i.e. C-7) were based soley on synthetic conve-
nience, see: (a) Wood, J. L.; Stoltz, B. M.; Dietrich, H.-J.;
Pflum, D. A.; Petsch, D. T. J. Am. Chem. Soc. 1997, 119,
9641–9651; (b) Wood, J. L.; Petsch, D. T.; Stoltz, B. M.;
Hawkins, E. M.; Elbaum, D.; Stover, D. R. Synthesis
1999, 1529–1533; (c) Petsch. D. T. Ph.D. Thesis, Yale

382
K. Tamaki et al. / Tetrahedron Letters 43 (2002) 379–382
13. (+)-Indolocarbazole 15 (isomer 1): a pale yellow powder;
[h]2D0 +68.7 (c 0.31, CHCl3); IR (thin film/NaCl) 3485 (br
m), 3333 (br m), 3056 (m), 2999 (m), 2928 (s), 2854 (m),
1732 (s), 1671 (s), 1585 (m), 1514 (s), 1451 (s), 1400 (s)
42.1, 33.5, 29.2, 28.9, 28.7, 28.6, 22.8, 21.5; HRMS (FAB)
m/z 728.3340 [calcd for C44H46N3O7 (M+H) 728.3336].
15. Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1996, 118, 100–110.
1
cm−1; H NMR (400 MHz, acetone-d6): l 9.76 (d, J=8.0
16. Due to signal overlap in 1H NMR, E/Z ratio was not
determined.
Hz, 1H), 8.14 (d, J=7.8 Hz, 1H), 7.94 (d, J=8.6 Hz,
1H), 7.88 (d, J=8.5 Hz, 1H), 7.51 (app t, J=7.7 Hz, 1H),
7.44 (app t, J=7.8 Hz, 1H), 7.35–7.27 (m, 2H), 7.16 (dd,
J=5.0, 7.3 Hz, 1H), 7.10 (d, J=1.9 Hz, 1H), 7.01 (dd,
J=1.9, 8.2 Hz, 1H), 6.91 (d, J=8.1 Hz, 1H), 5.60 (ddt,
J=10.2, 17.0, 6.8 Hz, 1H), 5.34 (d, J=14.9 Hz, 1H), 5.30
(app t, J=3.7 Hz, 1H), 5.26 (s, 1H), 4.81 (m, 1H), 4.76
(m, 1H), 4.42 (d, J=14.9 Hz, 1H), 4.00 (s, 3H), 3.77 (s,
3H), 3.75 (s, 3H), 3.49 (dd, J=7.3, 13.8 Hz, 1H), 2.53 (m,
1H), 2.42 (m, 1H), 2.26 (m, 1H), 2.23 (s, 3H), 1.82–1.74
(m, 2H), 1.13–0.94 (m, 7H), 0.52 (m, 1H); 13C NMR (100
MHz, CDCl3): l 173.9, 170.0, 149.2, 148.3, 139.9, 138.9,
137.2, 135.2, 130.4, 127.0, 126.7, 126.4, 125.6, 125.2,
125.1, 122.9, 122.5, 120.4, 120.4, 120.2, 120.0, 117.8,
114.3, 114.0, 112.8, 111.0, 110.9, 108.4, 98.5, 85.1, 84.6,
58.3, 55.9, 55.8, 54.0, 43.6, 41.7, 33.5, 29.2, 29.2, 28.7,
28.6, 22.9, 21.5; HRMS (FAB) m/z 728.3339 [calcd for
C44H46N3O7 (M+H) 728.3336].
17. (−)-(7S)-K252a dimer (2): a white powder: [h]2D0 −145 (c
0.10, CHCl3); IR (thin film/NaCl) 3223 (br m), 3051 (m),
2924 (s), 2851 (m), 1731 (s), 1678 (s), 1583 (m), 1487 (m),
1
1453 (s), 1392 (s) cm−1; H NMR (400 MHz, acetone-d6):
l 9.37 (d, J=7.8 Hz, 2H), 8.13 (d, J=7.8 Hz, 2H), 8.10
(s, 2H), 8.00 (d, J=8.5 Hz, 2H), 7.74 (d, J=8.3 Hz, 2H),
7.48–7.40 (m, 4H), 7.34 (app t, J=7.4 Hz, 2H), 7.26 (app
t, J=7.6 Hz, 2H), 7.12 (dd, J=4.8, 7.4 Hz, 2H), 5.38 (s,
2H), 5.33 (dd, J=2.2, 7.8 Hz, 2H), 4.00 (s, 6H), 3.49 (dd,
J=7.4, 14.0 Hz, 2H), 2.51 (m, 2H), 2.30 (dd, J=4.8, 14.0
Hz, 2H), 2.20 (s, 6H), 1.74 (m, 2H), 1.61 (m, 2H),
1.47–0.99 (m, 22H); 13C NMR (100 MHz, CDCl3): l
173.3, 171.1, 140.7, 137.0, 136.7, 129.3, 125.4, 125.3,
124.8, 123.7, 121.1, 120.8, 120.4, 118.7, 116.2, 115.9,
115.8, 113.4, 107.0, 100.0, 86.2, 85.0, 57.2, 53.1, 42.6,
34.2, 29.3, 29.2, 29.1, 28.7, 28.7, 26.6, 22.7; HRMS (FAB)
m/z 1129.5073 [calcd for C68H69N6O10 (M+H)
1129.5075].
14. (−)-Indolocarbazole 16 (isomer 2): a pale yellow powder;
[h]2D0 −30.0 (c 0.26, CHCl3); IR (thin film/NaCl) 3485 (br
m), 3334 (br w), 3056 (m), 2998 (m), 2928 (s), 2854 (m),
1732 (s), 1671 (s), 1585 (m), 1515 (s), 1487 (m), 1450 (s),
18. (+)-(7R)-K252a Dimer (3): a white powder: [h]2D0 +107 (c
0.10, CHCl3); IR (thin film/NaCl) 3499 (w), 3405 (br m),
3205 (br m), 3053 (m), 2924 (s), 2853 (s), 1732 (s), 1680
1400 (s) cm−1 1H NMR (400 MHz, acetone-d6): l 9.76
;
1
(s), 1584 (m), 1488 (w), 1458 (s), 1393 (s) cm−1; H NMR
(d, J=8.0 Hz, 1H), 8.16 (d, J=8, 1 Hz, 1H), 7.94 (d,
J=8.5 Hz, 1H), 7.88 (d, J=8.5 Hz, 1H), 7.51 (app t,
J=7.8 Hz, 1H), 7.44 (app t, J=7.7 Hz, 1H), 7.37–7.26
(m, 2H), 7.15 (dd, J=5.0, 7.3 Hz, 1H), 7.11 (d, J=1.8
Hz, 1H), 7.02 (dd, J=1.8, 8.1 Hz, 1H), 6.92 (d, J=8.1
Hz, 1H), 5.57 (ddt, J=10.2, 17.0, 6.8 Hz, 1H), 5.39 (s,
1H), 5.32 (d, J=15.1 Hz, 1H), 5.32 (app t, J=3.5 Hz,
1H), 4.78 (m, 1H), 4.75 (m, 1H), 4.43 (d, J=15.1 Hz,
1H), 4.00 (s, 3H), 3.76 (s, 3H), 3.75 (s, 3H), 3.54 (dd,
J=7.3, 13.8 Hz, 1H), 2.56 (m, 1H), 2.47–2.33 (m, 2H),
2.18 (s, 3H), 1.79–1.67 (m, 2H), 1.07–0.87 (m, 7H), 0.45
(m, 1H); 13C NMR (100 MHz, CDCl3): l 173.9, 170.0,
149.3, 148.3, 140.0, 138.9, 137.4, 135.1, 130.4, 127.1,
126.6, 126.6, 125.7, 125.3, 125.2, 122.7, 122.6, 120.6,
120.4, 120.2, 120.0, 118.1, 114.4, 114.0, 113.0, 111.1,
111.0, 108.3, 98.6, 85.1, 84.3, 58.3, 55.9, 55.9, 54.0, 43.6,
(400 MHz, acetone-d6): l 9.42 (d, J=8.0 Hz, 2H), 8.17 (s,
2H), 8.15 (d, J=8.3 Hz, 2H), 8.01 (d, J=8.4 Hz, 2H),
7.78 (d, J=8.3 Hz, 2H), 7.48 (app t, J=7.8 Hz, 2H), 7.44
(app t, J=7.9 Hz, 2H), 7.34 (app t, J=7.3 Hz, 2H), 7.28
(app t, J=7.6 Hz, 2H), 7.15 (dd, J=5.1, 7.3 Hz, 2H),
5.46 (s, 2H), 5.38 (dd, J=1.9, 8.1 Hz, 2H), 4.00 (s, 6H),
3.52 (dd, J=7.3, 14.3 Hz, 2H), 2.56 (m, 2H), 2.34 (dd,
J=5.1, 14.3 Hz, 2H), 2.20 (s, 6H), 1.74–1.55 (m, 6H),
1.53–1.06 (m, 20H); 13C NMR (100 MHz, CDCl3): l
174.0, 172.4, 140.2, 137.8, 137.1, 129.1, 126.8, 125.7,
124.9, 124.4, 124.2, 123.3, 122.1, 120.6, 120.1, 117.1,
115.0, 114.1, 107.3, 98.7, 85.1, 84.4, 57.7, 53.9, 41.9, 34.3,
29.3, 29.3, 29.2, 29.2, 29.2, 26.4, 22.9; HRMS (FAB) m/z
1129.5073 [calcd for C68H69N6O10 (M+H) 1129.5075].