Chemistry of renieramycins. Part 9: Stereocontrolled total synthesis of (±)-renieramycin G

Article abstract of DOI:10.1016/j.tetlet.2011.02.055

A 25-step stereocontrolled total synthesis of (±)-renieramycin G (1g) from readily available 2-hydroxy-3-methyl-4,5-dimethoxybenzaldehyde (3) is described. This synthesis features the concise construction of the pentacyclic framework using the stereoselective Pictet-Spengler type cyclization reaction of lactam (14) with ethyl diethoxyacetate, followed by the base-catalyzed isomerization of the C-1 stereo center.

Full text of DOI:10.1016/j.tetlet.2011.02.055

Tetrahedron Letters 52 (2011) 2446–2449
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Chemistry of renieramycins. Part 9: Stereocontrolled total synthesis of
( )-renieramycin G
⇑
Masashi Yokoya, Kimiko Shinada-Fujino, Naoki Saito
Graduate School of Pharmaceutical Sciences, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose, Tokyo 204-8588, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
A 25-step stereocontrolled total synthesis of ( )-renieramycin G (1g) from readily available 2-hydroxy-3-
methyl-4,5-dimethoxybenzaldehyde (3) is described. This synthesis features the concise construction of
the pentacyclic framework using the stereoselective Pictet–Spengler type cyclization reaction of lactam
(14) with ethyl diethoxyacetate, followed by the base-catalyzed isomerization of the C-1 stereo center.
Ó 2011 Elsevier Ltd. All rights reserved.
Received 12 January 2011
Revised 9 February 2011
Accepted 14 February 2011
Available online 20 February 2011
Keywords:
Renieramycin
Total synthesis
Natural marine product
Cytotoxicity
The tetrahydroisoquinoline family of natural products, includ-
ing saframycins, renieramycins,1 and the most notable example,
ecteinascidin 743,2,3 has generated wide chemical and biological
interests because of their novel structures and meager availability
in nature, and for their potent antitumor activity.4 Following the
discovery of renieramycins A–D (1a–d) from the Mexican blue
sponge Reniera sp. in 1982,5 more than 10 marine natural reniera-
mycins,6–10 along with jorumycin11 and jorunnamycins,12 were
isolated from several kinds of marine organisms. Renieramycins
are expected to be one of the candidates for new anticancer drugs.
However, the structure–activity relationships (SARs) of reniera-
mycins are little explored13 because these marine natural products
are available in very minute quantities (Fig. 1).
As part of our search for new metabolites via the isolation and
characterization of biologically active compounds from Thai mar-
ine animals, we successfully isolated renieramycin M (1m) in gram
OMe
OMe
OMe
OMe
O
H
Me
O
O
H
Me
Me
HO
H
O
H
Me
O
O
O
O
O
E
O
H
N
H
H
N
O
Me
Me
Me
O
OH
ND 14Me
Me
N
Me
X
3
N
Me
N
Me
X
A
B
C
O
N
O
N
X
H
H
H
MeO
MeO
H
MeO
21
1
MeO
H
H
H
H
Y
Y
O
O
O
O
O
22
NH
Me
H
O
Me
Me
O
O
O
O
H
O
H
Me
Me
Me
Me
renieramycins
renieramycins
saframycins
renieramycin H (1h)
(= cribrostatin 4)
A (1a): X = OH, Y = H
B (1b): X = OEt, Y = H
E (1e): X = H, Y = OH
F (1f): X = OMe, Y = OH
M (1m): X = H, Y = CN
C (1c): X = OH
D (1d): X = OEt
G (1g): X = H
A (2a): X = H, Y = CN
B (2b): X = Y = H
C (2c): X = OMe, Y = H
G (2g): X = OH, Y = CN
S (2s): X = H, Y = OH
Figure 1. Structures of bis-1,2,3,4-tetrahydroisoquinolinequinones and their related natural products.
⇑
Corresponding author. Tel./fax: +81 42 495 8794.
E-mail address: naoki@my-pharm.ac.jp (N. Saito).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.02.055

M. Yokoya et al. / Tetrahedron Letters 52 (2011) 2446–2449
2447
scale from the Thai blue sponge Xestospongia sp. by pretreatment
with potassium cyanide.14,15 We can provide a variety of reniera-
mycin derivatives from 1m for the investigation of SARs.1,16 We
are also very interested in the structures of renieramycin G (1g)
and cribrostatin 4 (= renieramycin H: 1h), because both com-
pounds maintained their cytotoxicity despite lack of the essential
functional group of hemiaminal or aminonitrile at C-21. In this pa-
per, we report our total synthesis of ( )-renieramycin G (1g) from
readily available 2-hydroxy-3-methyl-4,5-dimethoxybenzalde-
hyde (3) in 25 steps.
and then acetylation provided diacetate 7 (88%). Condensation of
7 with 4b29 in the presence of tBuOK gave (Z)-isomer 8 (89%).
The transformation of 8 into carbamate 9 was achieved in three
steps by the method developed in our synthetic approach to safra-
mycin A (2a) (73%).30 Partial reduction of the activated lactam
carbonyl group of 9 followed by cyclization gave (E)-1,5-imino-3-
benzazocine 1031 in 89% yield. Deprotection of 10 with trifluoro-
acetic acid (TFA) and H2SO4 gave (Z)-lactam 11 in 64% yield.32
Reductive N-methylation of 11 gave 12 in 93% yield, and reduction
of the double bond of 12 under the action of hydrogen (28 atm) on
20% Pd(OH)2/C in ethanol at 80 °C for 20 h occurred from the less
To date, four total syntheses of renieramycin G (1g)17–20 have
been reported, but most of those approaches were based on the
preparation of a bicyclic AB ring system and a 1,3-cis configuration
before a pentacyclic framework is constructed. Furthermore, the
total synthesis of cribrostatin 4 (1h) by three other groups involved
the preparation of a pentacyclic compound via a 1,13-cis stereoiso-
mer.21–23 Our synthesis of 1g followed closely the pathway we
established for saframycin B,24 N-acetylsaframycin Mx 2,25 and
renieramycin derivatives,26 in addition to the Pictet–Spengler type
cyclization reaction of the non-basic nitrogen of the secondary
amide with ethyl diethoxyacetate to construct the pentacyclic
framework. This strategy should provide a variety of novel ana-
logues of renieramycin as well as 1-epi-pentacyclic compound for
the detailed study of SAR of these classes of antitumor marine nat-
ural products.
hindered a-face to afford 13 in 89% yield.
According to the procedure of Ong and co-workers,33 treatment
of 13 with a large excess of paraformaldehyde in acetic acid/TFA
(4:1) at 80 °C for 15 h provided 14 in 66% yield. The stereochemis-
try of 14 was readily identified on the basis of the chemical shifts of
H-4b (d 2.19) and H-3 (d 3.90), along with the coupling between H-
4b and H-3 (J = 12.5 Hz), as noted previously for related systems.34
The next stage of the investigation involved the establishment
of a method to construct a pentacyclic framework having a
hydroxymethyl substituent at C-1 using the modified Pictet–Spen-
gler reaction via the O-trimethylsilyllactim intermediate with ethyl
diethoxyacetate. Encouraged by the results of our recent model
conversion,35 we first treated 13 with trimethylsilyl chloride
(TMSCl) and TEA in dichloroethane at 25 °C for 2 h and followed
by treatment with ethyl diethoxyacetate in the presence of tri-
methylsilyl trifluoromethanesulfonate (TMSOTf) at the same tem-
perature for 17 h and finally refluxed for 42 h. However, this
gave an inseparable mixture of several products. On the other
Phenol 327 was protected with a methoxymethyl (MOM) group
to afford 4a (Scheme 1), the condensation of which with diacetate
528 in the presence of a base gave (Z)-arylidenepiperazinedione 6
(73%). Catalytic hydrogenation of 6 over 5% Rh/C in 2-propanol
O
TsO
O
Ac
N
Me
H
OMe
N
Ac
MeO
OMe
O
O
OMe
O
O
OMe
5
O
b
4b
MeO
e
H
Ac
OMe
Me
OMe
H
a
c, d
N
N
Me
N
N
O
OR
Ac
Ac
Me
OMOM
OMOM
3: R = H
6
7
4a: R = MOM
MeO
Me
TsO
OMe
OMe
CO2Pri
OMe
MeO
H
Me
TsO
O
OMe
TsO
O
O
Ac
f - h
Me
OMe
Me
Me
MeO
OMe
Me
OH
i, j
CO2Pri
N
N
N
N
N
N
O
MeO
H
H
MeO
O
OMOM
MeO
OMOM
9
8
10
MeO
MeO
OMe
OMe
OMe
MeO
Me
OH
MeO
Me
OH
MeO
Me
OH
TsO
H
TsO
H
TsO
H
H
4
1
H
Me
MeO
Me
MeO
k
m
Me
MeO
N
R
n
N
Me
N
Me
3
N
N
O
N
H
H
H
H
H
MeO
l
O
MeO
MeO
O
11: R = H
13
14
12: R = Me
Scheme 1. Reagents and conditions: (a) NaH, DMF, then MOMCl, 25 °C, 2 h, 100%; (b) tBuOK, tTBuOH, CH2Cl2, 25 °C, 1 h, 73%; (c) H2, 5% Rh/C, 25 °C, 2-propanol, 14 h; (d) Ac2O,
pyridine, DMAP, 25 °C, 2.5 h, 88% (2 steps); (e) tBuOK, tBuOH, THF, 5.5 h, 89%; (f) NaH, DMF, 0 °C, 0.5 h, then 4-MeOC6H4CH2Cl, 25 °C, 17 h; (g) 5%NaHCO3/H2O, EtOH, reflux,
2.5 h; (h) ClCO2Pri, TEA, DMAP, CH2Cl2, 25 °C, 23 h, 73% (3 steps); (i) Li(tBuO)3AlH, THF, 0 °C, 4.5 h; (j) HCO2H, 60 °C,1 h, 89% (2 steps); (k) H2SO4, TFA, 25 °C, 20 h, 64%; (l) 37%
HCHO–H2O, HCO2H, 70 °C, 1 h, 93%; (m) H2 (28 atm), 20% Pd(OH)2/C, EtOH, 80 °C, 20 h, 89%; (n) (HCHO)n, AcOH/TFA (4:1), 80 °C, 15 h, 66%.

2448
M. Yokoya et al. / Tetrahedron Letters 52 (2011) 2446–2449
OMe
OMe
MeO
Me
MeO
Me
OH
R1O
H
HO
H
H
H
o
p
r - u
Me
OR2
Me
N
N
Me
Me
13
1
N
N
O
MeO
MeO
H
H
H
MeO
O
O
MeO
O
15
Me
16a: R1 = Ts, R2 = H
16b: R1 = R2 = H
q
OMe
OMe
16c: R1 = R2 = Bn
MeO
Me
MeO
Me
BnO
MeO
H
BnO
MeO
H
H
N
H
H
v
Me
OBn
Me
MeO
OBn
N
Me
N
Me
17a
+
N
MeO
H
H
O
O
H
O
O
17a
17b
OMe
OMe
MeO
Me
O
H
Me
O
HO
H
O
H
H
N
Me
OH
Me
y
w, x
Me
MeO
z
N
N
Me
renieramycin G
1g
17b
N
MeO
H
H
MeO
O
O
O
OH
OH
18
19
Scheme 2. Reagents and conditions: (o) NH2NH2–H2O, MeOH, reflux, 73 h, 80%; (p) (EtO)2CHCO2Et (4 equiv), TMSOTf (8 equiv), (CH2Cl)2, reflux, 19 h, 76%; (q) BnBr, K2CO3,
acetone, reflux, 12 h, 88%; (r) 0.1 M LiOH/H2O, THF–MeOH (3:1), 25 °C, 8 days; (s) ClCO2Et, TEA, THF, À7 °C, 3 h; (t) NaBH4, H2O, 0 °C, 2 h, 81% (3 steps); (u) (COCl)2, DMSO,
CH2Cl2, À78 °C, then TEA was added at À40 °C, 92%; (v) DBU (1 equiv), THF, 24 h 95% (17a/17b = 1:2); (w) NaBH3CN, THF, AcOH, 25 °C, 3.5 h, 64%; (x) H2, 20% Pd(OH)2/C,
MeOH, 25 °C, 2 h, 100%; (y) CAN, MeCN–H2O, 0 °C, 70%; (z) (Z)-MeCH@C(Me)COCl, CH2Cl2, 25 °C, 24 h, 51%.
hand, the reaction of 13 with ethyl diethoxyacetate in the presence
of TMSOTf in dichloroethane under reflux for 21 h gave 16a with a
maximum yield of only 28%. Thus, we attempted to increase the
reactivity of the A-ring, such as phenol 15, which was easily pre-
pared from 13 (80%) (Scheme 2). The reaction of 15 under the same
conditions described above gave 16b in 76% yield. The X-ray crys-
tallographic analysis revealed that the stereochemistry at C-1 was
epimeric to that of natural renieramycins (Fig. 2).36
Having succeeded in the construction of the pentacyclic frame-
work of 1g, the remaining subject was the isomerization at C-1 of
16b. Because 16b is not sufficiently soluble in any solvent, it was
better to convert 16b into 16c before starting our study of the
isomerization at C-1. Furthermore, the C-1 ester of 16c should be
oriented in the -axial direction because the b-equatorial space
a
was hindered by both the methoxyl group at the peri position
and the lactam carbonyl at C-21. Indeed, numerous efforts to epi-
merize 16c under basic conditions were unsuccessful, but this
problem was solved by using the smallest carbonyl functional
group at C-1. Treatment of ester 16c with aqueous LiOH in THF/
MeOH (3:1) at 25 °C for 8 days gave the corresponding carboxylic
acid, which was subsequently subjected to hydride reduction via
a mixed anhydride to afford the alcohol. The Swern oxidation of
the alcohol afforded aldehyde 17a in 75% overall yield. Treating
17a with DBU in THF at 25 °C for 24 h gave 17b and 17a in 62%
and 33% yields, respectively. The 1H NMR spectrum of 17b dis-
played an H-1 signal that appeared as a singlet at d 6.06 and an
H-3 signal at d 3.92, whereas the 1H NMR spectrum of 17a showed
an H-1 signal at d 6.27 and an H-3 signal at d 4.18. The remarkable
difference in the chemical shifts of the methine protons must be
due to the steric interactions between the side chains at C-1 and
C-3 (Fig. 3).37 Reduction of 17b with sodium cyanoborohydride
(NaBH3CN) in THF in the presence of a catalytic amount of AcOH,
followed by debenzylation, gave 18 in 64% yield over two steps.
Oxidation of 18 with ceric ammonium nitrate (CAN) in aqueous
acetonitrile afforded Magnus intermediate 1917 in 70% yield.
According to the method of Magnus, treatment of 19 with angeloyl
chloride in CH2Cl2 gave ( )-renieramycin G (1g) in 51% yield. Syn-
thetic 1g was identical with the natural one on comparison of their
spectroscopic data along with the authentic chart of the racemic
one by Magnus.17,38
In summary, we have achieved the total synthesis of ( )-renie-
ramycin G in 25 steps in 1.0% overall yield.
Application of this approach for the synthesis of other members
of the renieramycin family, including renieramycins B and D and
Figure 2. ORTEP drawing of compound 16b.

M. Yokoya et al. / Tetrahedron Letters 52 (2011) 2446–2449
OMe
2449
OMe
OMe
MeO
Me
MeO
Me
Me
MeO
H
BnO
MeO
H
MeO
H
H
H
H
N
Me
OMe
Me
OBn
Me
N
Me
N
Me
3
N
Me
1
N
N
MeO
H
MeO
H
MeO
H
MeO
O
H
O
OBun
MeO
O
O
OBun
17a: C-1, C-3 trans
17b: C-1, C-3 cis
20a: C-1, C-3 trans
20b: C-1, C-3 cis
21a: C-1, C-3 trans
21b: C-1, C-3 cis
17
2024
2137
a
b
a
b
a
b
H-1
H-3
6.27
4.18
6.09
3.92
4.56
3.57
4.09
2.84
4.58
3.61
4.10
2.84
Figure 3. Comparison of 1H NMR chemical shifts of natural form b series with those of unnatural a series.
21. Chan, C.; Heid, R.; Zheng, S.; Guo, J.; Zhou, B.; Furuuchi, T.; Danishefsky, S. J. J.
Am. Chem. Soc. 2005, 127, 4596–4598.
22. Vincent, G.; Williams, R. M. Angew. Chem., Int. Ed. 2007, 46, 1517–1520.
23. Chen, X.; Zhu, J. Angew. Chem., Int. Ed. 2007, 46, 3962–3965.
24. Kubo, A.; Saito, N.; Yamato, H.; Masubuchi, K.; Nakamura, M. J. Org. Chem. 1988,
53, 4295–4310.
cribrostatin 4, together with the corresponding C-1 epimers, are
under study in our laboratories.
Acknowledgments
25. Saito, N.; Harada, S.; Inouye, I.; Yamaguchi, K.; Kubo, A. Tetrahedron 1995, 51,
8231–8246.
This work was supported by the Japan Society for the Promotion
of Science (JSPS) Asia and Africa Scientific Platform Program
(2010–2012), and partially supported by a Grant from the High-
Tech Research Center Project, the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan (No. S0801043).
26. Saito, N.; Yamauchi, R.; Kubo, A. Heterocycles 1991, 32, 1203–1214.
27. Our starting material for the E-ring portion of 1g was the commercially
available 3,4-dimethoxyphenol, the phenolic OH protection of which followed
by three steps (a) n-BuLi, MeI, THF, 0 °C; (b) HCl/EtOH; (c)
hexamethylenetetramine (HMPT), AcOH gave 3 in 66% overall yield.
28. Kubo, A.; Saito, N.; Yamato, H.; Kawakami, Y. Chem. Pharm. Bull. 1987, 35,
2525–2532.
References and notes
29. Aldehyde 4b was prepared from 3 in quantitative yield (TsCl, TEA, CH2Cl2, 0 °C).
30. Saito, N.; Yamauchi, R.; Nishioka, H.; Ida, S.; Kubo, A. J. Org. Chem. 1989, 54,
5391–5395.
1. Part 8: Charupant, K.; Daikuhara, N.; Saito, E.; Amnuoypol, S.; Suwanborirux, K.;
Owa, T.; Saito, N. Bioorg. Med. Chem. 2009, 17, 4548–4558.
2. Rinehart, K. L. Med. Drug Rev. 2000, 102, 1669–1730.
3. Aune, G. J.; Furuta, T.; Pommier, Y. Anticancer Drugs 2002, 13, 545–555.
4. Scott, J. D.; Williams, R. M. Chem. Rev. 2002, 102, 1669–1730.
5. Structures of renieramycins A–D (1a–d): Frincke, J. M.; Faulkner, D. J. J. Am.
Chem. Soc. 1982, 104, 265–269. errata: 1982, 104, 5004.
6. Structures of renieramycins E (1e) and F (1f): He, H.-Y.; Faulkner, D. J. J. Org.
Chem. 1989, 54, 5822–5824.
31. The E stereochemical assignment of 10 was based on the 1H NMR signal of the
methine proton (d 6.55), which was positioned in the deshielding zone of the
aromatic ring of the side chain and the carbonyl group of N-CO2Pri.
32. The NMR spectrum of 11 displayed H-1 proton as a singlet at d 4.95 and C-1
carbon at d 48.0.
33. Chang, Y.-A.; Sun, T.-H.; Chiang, M. Y.; Lu, F.-J.; Huang, Y.-T.; Liang, L.-C.; Ong, C.
W. Tetrahedron 2007, 63, 8781–8787; Ong, C. W.; Chang, V. A.; Wu, J.-Y.; Cheng,
C.-C. Tetrahedron 2003, 59, 8245–8249; Ong, C. W.; Lee, H. C. Aust. J. Chem.
1990, 43, 773–775.
34. Saito, N.; Seki, R.; Kameyama, N.; Sugimoto, R.; Kubo, A. Chem. Pharm. Bull.
2003, 51, 821–831.
7. Structure of renieramycin G (1g): Davidson, B. S. Tetrahedron Lett. 1992, 33,
3721–3724.
8. Structures of renieramycins H (1h)9 and I (1i): Parameswaran, P. S.; Naik, C. G.;
Kamat, S. Y.; Pramanik, B. N. Indian J. Chem., Sect B 1998, 37, 1258–1263.
9. The revised structure of 1h is the same as that of cribrostatin 4: Saito, N.; Sakai,
H.; Suwanborirux, K.; Pummangura, S.; Kubo, A. Heterocycles 2001, 55, 21–28.
10. Structure of cribrostatin 4: Pettit, G. R.; Knight, J. C.; Collins, J. C.; Herald, D. L.;
Pettit, R. K.; Boyd, M. R.; Young, V. G. J. Nat. Prod. 2000, 63, 793–798.
11. Structure of jorumycin: Fontana, A.; Cavaliere, P.; Wahidulla, S.; Naik, C. G.;
Cimino, G. Tetrahedron 2000, 56, 7305–7308.
35. Yokoya, M.; Kawachi, O.; Saito, N. Heterocycles 2008, 76, 1497–1509.
36. X-ray crystallographic analysis of 16. All measurements were performed on a
Rigaku AFC7S diffractiometer with graphite-monochromated CuK
a radiation
(k = 1.54178 Å). Crystal data: colorless prismatic crystal, triclinic, C29H36N2O9
ꢀ
(Mr = 556.61), space group P1 (#2) with a = 8.807 (5) Å, b = 9.357 (4) Å,
c = 18.742 (6) Å,
a = 88.05 (3)°, b = 86.28 (3)°, c
= 66.64 (4)°, V = 1415 (1) Å3,
Z = 2, and Dcalcd = 1.306 g/cm3. The final cycle of full-matrix least-squares
refinement was based on 3691 unique reflections (2 < 136.1°) and 398 variable
parameters and converged with unweighted and weighted agreement factors
12. Structures of jorunnamycins A–C: Charupant, K.; Suwanborirux, K.;
Amnuoypol, S.; Saito, E.; Kubo, A.; Saito, N. Chem. Pharm. Bull. 2007, 55, 81–86.
13. A few SAR studies on renieramycins were reported by using some synthetic
derivatives: Lane, J. W.; Estevez, A.; Mortara, K.; Callan, O.; Spencer, J. R.;
Williams, R. M. Bioorg. Med. Chem. Lett. 2006, 16, 3180–3183; Wright, B. J. D.;
Chan, C.; Danishefsky, S. J. J. Nat. Prod. 2008, 71, 409–414.
14. Suwanborirux, K.; Amnuoypol, S.; Plubrukarn, A.; Pummangura, S.; Kubo, A.;
Tanaka, C.; Saito, N. J. Nat. Prod. 2003, 66, 1441–1446.
15. Amnuoypol, S.; Suwanborirux, K.; Pummangura, S.; Kubo, A.; Tanaka, C.; Saito,
N. J. Nat. Prod. 2004, 67, 1023–1028.
16. Saito, N.; Tanaka, C.; Koizumi, Y.; Suwanborirux, K.; Amnuoypol, S.;
Pummangura, S.; Kubo, A. Tetrahedron 2004, 60, 3873–3881.
17. Magnus, P.; Matthews, K. S. J. Am. Chem. Soc. 2005, 127, 12476–12477.
18. Lane, J. W.; Chen, Y.; Williams, R. M. J. Am. Chem. Soc. 2005, 127, 12684–12690.
19. Wu, Y. -C.; Zhu, J. Org. Lett. 2009, 11, 5558–5561.
of R = 0.078, Rw = 0.212, and R1 = 0.075 for I > 2.0r(I)data.
37. For previous data See Figure 3: Saito, N.; Harada, S.; Yamashita, M.; Saito, T.;
Yamaguchi, K.; Kubo, A. Tetrahedron 1995, 51, 8213–8230.
38. ( )-Renieramycin G (1g): dark orange powder, 1H NMR (C6D6) d 5.56 (1H, ddd,
J = 2.6, 2.4, 1.8 Hz, 1-H), 5.35 (1H, qq, J = 7.3, 1.5 Hz, 26-H), 4.92 (1H, dd,
J = 11.7, 2.6 Hz, 22-H), 4.52 (1H, dd, J = 11.7, 2.4 Hz, 22-H), 3.82 (1H, d,
J = 3.9 Hz, 11-H), 3.79 (3H, s, 7-OMe), 3.63 (3H, s, 17-OMe), 3.48 (1H, dd, J = 7.2,
0.6 Hz, 13-H), 3.36 (1H, ddd, J = 12.0, 3.9, 2.4 Hz, 3-H), 3.10 (1H, J = 16.5, 2.4 Hz,
4-Ha), 2.87 (1H, dd, J = 20.7, 0.6 Hz, 14-Hb), 2.60 (1H, dd, J = 20.7, 7.2 Hz, 14-
Ha), 1.90 (3H, s, 6-Me), 1.87 (3H, s, 16-Me), 1.80 (3H, s, NMe), 1.55 (3H, dq,
J = 7.3, 1.5 Hz, 26-Me), 1.51 (1H, ddd, J = 16.5, 12.0, 1.8 Hz, H-4b), 1.37 (3H, dq,
J = 1.5, 1.5 Hz, 25-Me); FABMS m/z 565 (MH+); HRFABMS m/z 565.2183 (MH+,
calcd for C30H33N2O9, 565.2186). IR (KBr) 1717, 1655, 1616 cmÀ1
.
20. Liao, X. W.; Liu, W.; Dong, W. F.; Guan, B. H.; Chen, S. Z.; Liu, Z. Z. Tetrahedron
2009, 65, 5709–5715.