Total synthesis of the proposed structure of decurrenside D

Article abstract of DOI:10.1016/j.tetlet.2015.08.003

A chiron approach for the total synthesis of the proposed structure of decurrenside D is reported. The construction of the 3-deoxy-d-manno-2-octulosonic acid framework (KDO derivative) was achieved by the transformation of the respective C-allylated-ribofuranose derivative into its corresponding α-keto acid ester derivative. Accordingly, the crucial step of this total synthesis is the application of the stereoselective nucleophilic substitution at the anomeric position (NSAP) reaction to the 5-O-benzoyl ribofuranose derivative. Both optical rotation and NMR data of the synthesized decurrenside D are inconsistent with the proposed structure.

Full text of DOI:10.1016/j.tetlet.2015.08.003

Tetrahedron Letters 56 (2015) 5416–5418
Contents lists available at ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Total synthesis of the proposed structure of decurrenside D
⇑
Verónica González-Márquez, Silvano Cruz-Gregorio, Jacinto Sandoval-Lira, Leticia Quintero ,
Fernando Sartillo-Piscil
⇑
Benemérita Universidad Autónoma de Puebla (BUAP), Facultad de Ciencias Químicas, 14 Sur Esq. San Claudio, San Manuel. 72570, Puebla, Mexico
a r t i c l e i n f o
a b s t r a c t
Article history:
A chiron approach for the total synthesis of the proposed structure of decurrenside D is reported. The con-
Received 10 July 2015
Revised 30 July 2015
Accepted 5 August 2015
Available online 8 August 2015
struction of the 3-deoxy-
transformation of the respective C-allylated-ribofuranose derivative into its corresponding
ester derivative. Accordingly, the crucial step of this total synthesis is the application of the stereoselec-
tive nucleophilic substitution at the anomeric position (NSAP) reaction to the 5-O-benzoyl ribofuranose
derivative. Both optical rotation and NMR data of the synthesized decurrenside D are inconsistent with
the proposed structure.
D
-manno-2-octulosonic acid framework (KDO derivative) was achieved by the
-keto acid
a
Keywords:
Chiron approach
Decurrensides
Ó 2015 Elsevier Ltd. All rights reserved.
Nucleophilic substitution at the anomeric
position
Proposed structure
Total synthesis
Decurrenside D, and also its four congeners (A, B, C, and E), were
ribofuranose derivative 3, and this latter compound by a stereose-
recently isolated from the methanolic extracts of the plant Solidago
decurrens by Kuono and coworkers. These plants have been used
lective nucleophilic substitution at the anomeric position (NSAP) of
a-D-ribofuranose derivative 4 (Scheme 1).
1
3,4
in Chinese traditional herbal medicine as diuretic, choleretic,
antiseptic, and also for wound healing.1 The molecular structure
of decurrenside D possesses a unique dioxabicyclo [3.2.1] octane
moiety fused on a KDO derivative skeleton at the C4 and C6 posi-
Ribofuranose derivative 4 was prepared in three steps from a-D-
allofuranose 5. Benzylation of 5 (benzyl bromide/NaH) gave
5
allofuranose derivative 6 (90% yield), which was submitted to a
6
sequential hydrolysis–dehomologation–reduction procedure to
2
tions. The molecular structure was established by 1D and 2D
afford ribofuranose 7 in 75% overall yield. After benzoylation of 7
NMR spectra analyses and by comparison with spectroscopic data
of known compounds. Furthermore, the bicyclic system was sug-
gested by the degree of unsaturation in the molecular formula
under standard conditions, the
obtained. Compound 4 was subjected to NSAP reaction (8–10 equiv
of allyltrimethylsilane (ATMS), 6 equiv of BF in CH Cl at 0 °C),
a-D-ribofuranose derivative 4 was
3
ÁOEt
2
2
2
and by the presence of carbon acetal (d
C
104.9 ppm). The HMBC
the expected allylated product 8 was obtained in low yield (8%)
correlation between H-4 and C-7 indicated an ether bond between
C-4 and C-7, while the NOESY correlation between hydroxyl groups
at C-2 and C-5 suggested endo orientation (Fig. 1).
along with an unexpected allylated/debenzylated product 9, as the
As part of a project directed to the synthesis of biological impor-
tant natural products which contains the furanoside ring,3 we got
interested, not only on the unique molecular structure of decurren-
sides but also in their probable biological activity. Consequently,
decurrenside D was selected as the initial target. We planned to
access to the KDO structure of decurrenside D by simple hydrolysis
8
H
7
1
R O
O
6
O
O
3
4
5
OR2
2
1
H
OH
= E-Cinnamoyl; R
OH
reaction of the
a
-keto acid ester (1), which would be prepared by
R
1
2
= Butyl: Decurrenside A
1
2
selective oxidation of triple bond of C-propargylated ribofuranose
derivative (2). Synthesis of 2 would be achieved from C-allylated
R = E-Cinamoyl; R = Methyl: Decurrenside B
R = Z-Cinnamoyl;R = Methyl: Decurrenside C
R = Benzoyl; R = Methyl: Decurrenside D
R = Benzoyl; R = Butyl: Decurrenside E
1
2
1
2
1
2
⇑
Corresponding authors.
E-mail address: ferando.sartillo@correo.buap.mx (F. Sartillo-Piscil).
Figure 1. Proposed structures of decurrensides.
http://dx.doi.org/10.1016/j.tetlet.2015.08.003
040-4039/Ó 2015 Elsevier Ltd. All rights reserved.
0

V. González-Márquez et al. / Tetrahedron Letters 56 (2015) 5416–5418
5417
O
O
O
O
O
O
Ph
O
O
Ph
O
Ph
O
O
Ph
O
O
Ph
O
O
O
O
O
O
O
O
O
OMe
OMe
O
BnO
O
OH
O
O
OH
O
C-Propargylated
ribofuranose
derivative
a-D-Ribofuranose
derivative
(4)
a-Keto acid ester
1)
C-Allylated
ribofuranose
derivative
Decurrenside D
(
(
2)
(3)
Scheme 1. Retrosynthetic plan for the proposed structure of decurrenside D.
major product.3,4 Interestingly, by diluting the reaction mixture at
0
.2 M the compound 9 resulted as the minor product (Scheme 2).
Table 1
Representative NMR data of natural and synthetized decurrenside D
The stereochemical outcome of the NSAP follows the Woerpel’s
3
e,7
Naturala
Synthetizeda
‘
inside attack’ model,
major product. Diol 9 was protected with 2,2-dimethoxypropane
2,2-DMP) to obtain the desired C-allylated ribofuranose
derivative 3. Transformation of into the C-propargylated
ribofuranose 2 was accomplished in two steps with good yields:
dibromination with Br in CCl followed by double
dehalogenation with DBU in DMF. The -keto acid ester 1,
whereby the 1,3-cis stereoisomer is the
Position
a
-Anomer
b-Anomer
(J in
(
d
H
(J in Hz)
d
C
d
H
(J in Hz)
d
C
d
H
d
C
3
Hz)
1
2
3
169.60
104.90
40.40
172.10
105.50
45.10
172.0
105.60
46.40
2
4
a
2.25, dd
(14.8, 5.0)
2.25, d
(14.5)
2.55, dd
(14.7, 2.9)
2.58, dd
(14.6, 2.5)
4.89, dd
(4.0, 2.7)
precursor of the proposed decurrenside D, was prepared
following another two-step protocol: C–H bromination with NBS
2
.31, dd
14.8, 1.8)
4.14, t
5.0)
2.66, dd
(14.5, 6.0)
4.85, ddd
(6.3, 4.4,
0.9)
(
and AgNO
the presence of NaHCO
hydrolysis of 1 with aqueous acetic acid gave a white solid
mp = 173–175 °C), which did not match neither the optical rota-
3
, and selective triple bond oxidation with KMnO
4
in
4
5
65.80
69.50
83.10
86.60
82.80
84.40
8
3
, MgSO and methanol. Finally, acetonide
4
(
(
4.04, t
5.0)
4.69, t
(4.6)
4.72,
apparent t
(
tion value nor the NMR data (Scheme 2).
(
4.0)
Whereas the natural compound shows the presence of a single
4.08b
b
6
7
4.48, t
5.0)
4.42, ddd
8.4, 5.0,
.2)
4.78, dd
12.4, 3.2)
78.40
81.0
74.30
80.0
4.01
74.20
79.50
1
13
anomer, the H and C NMR spectra of the synthetized compound
displayed a mixture of two compounds, presumably a mixture of
(
4.40, ddd
(9.1, 5.6,
2.5)
4.08b
(
3
a
-and b-anomers with an equimolar ratio in methanol and 1.5:1
in CDCl (Scheme 2). Representative NMR data of both natural
3
8
65.10
4.32,
65.30
4.33,
65.60
and synthetic decurrenside D is shown in Table 1. Although NMR
data of synthetized decurrenside D do not match to that of the nat-
ural substance, the analysis of 13C NMR of C1 and C2, and also cou-
pling constants of geminal hydrogen atoms at C3 revealed the
closest correlation. The major differences are manifested in the
dioxabicyclo [3.2.1] octane skeleton. Interestingly, while the anal-
(
apparent
d (12.0)
4.63, dd
(12.0, 2.5)
apparent
d (12.0)
4.59,
apparent
d (12.0)
5.02, dd
12.4, 8.4)
(
a
1H NMR (500 MHz) and 13C NMR (125 MHz) data in CD
Overlapped signals.
3
OD.
b
1
13
ysis of the H– C HMBC spectrum showed correlation between C2
O
OQ
OBz
OBz
O
O
O
O
O
O
i) H
ii) NaBH
5%
5
IO
6
, EtOAc
4
O
ATMS
BF3 OEt2
+
RO
O
, EtOH
BnO
O
7
CH
Cl
BnO
2
2
OH
HO
R = H; 5
BnBr, NaH
90%)
OH
Q = H; 7
Q = Bz; 4
BzCl, Py
(85%)
8
9
(
R = Bn; 6
8% at 0.3 M
0% at 0.2 M
80%
20%
5
OBz
O
OBz
BzO
Y
O
O
C
O
KMnO
4
, NaHCO
3
,
O
2
,2-DMP
2 4
i)Br ,CCl
9
MgSO , MeOH/H O
4
6
2
p-TSA
ii) DBU, DMF
60% two steps
5%
O
solvent
O
O O
OMe
O
O
free
Y = H; 2
Y= Br; 10
NBS, AgNO
64%
3
8
0%
3
1
Ph
Ph
O
O
O
O
O
O
7
0% aq. AcOH
+
OMe
O
1
O
O
OH
58%
OH
α-Decurrenside D
OH
OH
O
OMe
β-Decurrenside D
Ratio α/β: 1/1 in methanol; and 1.5/1 in CDCl
3
Withe solid (Mp = 173-175 °C). [α]
Lit. Colorless gum. Single α-anomer. [α]
D
= +35.8 (c = 0.7, MeOH).
= -11.7 (c = 0.1, MeOH).
1
D
Scheme 2. Synthesis of the proposed structure of decurrenside D.

5
418
V. González-Márquez et al. / Tetrahedron Letters 56 (2015) 5416–5418
Ph
O
Acknowledgments
O
O
O
We thank financial support from CONACYT (Project number:
179074; V.G.-M. thanks for PhD scholarship number: 328651)
and Benemérita Universidad Autónoma de Puebla (BUAP-VIEP).
We also thank professor Rodney Fernandes of Indian Institute of
Technology Bombay for helpful discussions.
O
Ph
O
Ph
O
6
O
HO
5
4
O
6
O
O
OH
O
3
O
2
5
4
2
3
OMe
OMe
O
OH
OH
HO
OH
O
MeO
Decurrenside D
Decurrenside D
3.2.1]
pyranoseform
Synthetic Decurrenside
[
(acyclic form)
Supplementary data
[
3.3.0]
furanose form
4
.77 kcal/mol
0.0 kcal/mol
Supplementary data (experimental section and copies of spec-
tra for new compounds and tables of atom coordinates of the min-
ima obtained at B3LYP/6-31+G(d,p) level theory for proposed
Decurrenside D in bicyclic [3.2.1] and [3.3.0] structural forms)
associated with this article can be found, in the online version, at
http://dx.doi.org/10.1016/j.tetlet.2015.08.003.
References and notes
1.
2.
3.
Shiraiwa, K.; Yuan, S.; Fujiyama, A.; Matsuo, Y.; Tanaka, T.; Jiang, Z. H.; Kuono, I.
J. Nat. Prod. 2012, 75, 88–92.
A similar molecular structure has been synthesized for enzymatic reactions:
Tikad, A.; Vincent, S. P. Eur. J. Org. Chem. 2013, 7593–7603.
(a) Cortezano-Arellano, O.; Quintero, L.; Sartillo-Piscil, F. J. Org. Chem. 2015, 80,
2
601–2608; (b) Sánchez-Eleuterio, A.; Quintero, L.; Sartillo-Piscil, F. J. Org.
Scheme 3. Molecular structures of the proposed decurrenside D, and optimized
structures in methanol ( = 32.613) using PCM at B3LYP/6-31+G(d,p) level theory.
Chem. 2011, 76, 5466–5471; (c) Cruz-Gregorio, S.; Espinoza-Rojas, C.; Quintero,
L.; Sartillo-Piscil, F. Tetrahedron Lett. 2011, 52, 6370–6371; (d) Paz-Morales, E.;
Melendres, R.; Sartillo-Piscil, F. Carbohydr. Res. 2009, 344, 1123–1126; (e)
Hernández-García, L.; Quintero, L.; Höpfl, H.; Sosa, M.; Sartillo-Piscil, F.
Tetrahedron 2009, 65, 139–144; (f) Sartillo-Meléndez, C.; Cruz-Gregorio, S.;
Quintero, L.; Sartillo-Piscil, F. Lett. Org. Chem. 2006, 3, 504–509.
e
and H5 for one of the ‘anomers’; the correlation between C2 and
H6 (evidence of which was observed in the natural product) was
not observed (see Supplementary material). These lines of evidence
suggest that the proposed decurrenside D could exist as a bicyclic
4
.
García-Tellado, F.; De Armas, P.; Marrero-Tellado, J. J. Angew. Chem., Int. Ed.
2
000, 39, 2727–2729.
5. Although the -allofuranose derivative 5 can be obtained from commercial
sources, we rather prefer to obtain it from diaceton- -glucose following a two-
a-D
D
[
3.3.0] octane glycoside structure, and also as a mixture of epimers
step procedure: Cruz-Gregorio, S.; Hernández, L.; Vargas, M.; Quintero, L.;
Sartillo-Piscil, F. J. Mex. Chem. Soc. 2005, 49, 20–23.
6. Xie, M.; Berges, D. A.; Robins, M. J. J. Org. Chem. 1996, 61, 5178–5179.
9
at the C2 position. This is interesting because suggest that this
unprecedented proposed structure (KDO derivative), prefers the
furanose form over the pyranose form, even though the latter is
considered as the thermodynamic structure.10 This unexpected
behavior might be attributed to the conformational strain imposed
by the dioxabicyclo moiety, which according to DFT calculations
7
.
(a) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Woerpel, K. A. J. Am. Chem. Soc.
999, 121, 12208–12209; (b) Larsen, C. H.; Ridgway, B. H.; Shaw, J. T.; Smith, D.
M.; Woerpel, K. A. J. Am. Chem. Soc. 2005, 127, 10879–10884.
8. Li, L. S.; Wu, Y. L. Tetrahedron Lett. 2002, 43, 2427–2430.
Voigt, B.; Mahrwald, R. Chem. Commun. 2014, 817–819.
1
9.
1
0. Stick, R. V.; Williams, S. J. Carbohydrates: The Essential Molecules of Life, 2nd ed.;
[
Geometry optimizations for conformers were performed at
Elsevier: Amsterdam, 2009. pp 15–25.
11. (a) Becke, A. D. J. Am. Chem. Phys. 1993, 98, 5648; (b) Lee, C.; Yang, W.; Parr, R.
G. Phys. Rev. B 1988, 37, 785.
1
1
12
B3LYP/6-31+G(d,p)
0
with PCM
(methanol) using Gaussian
1
3
9 ], the furanose form is 4.77 kcal/mol more stable than the
1
1
2. Tomasi, J.; Mennucci, B.; Cammi, R. Chem. Rev. 2005, 105, 2999–3093.
3. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.;
Cheeseman, J. R.; Scalmani, G.; Barone, V.; Mennucci, B.; Petersson, G. A.;
Nakatsuji, H.; Caricato, M.; Li, X.; Hratchian, H. P.; Izmaylov, A. F.; Bloino, J.;
Zheng, G.; Sonnenberg, J. L.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.;
Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Vreven,
T., ; Montgomery, J. A., Jr.; Peralta, J. E.; Ogliaro, F.; Bearpark, M.; Heyd, J. J.;
Brothers, E.; Kudin, K. N.; Staroverov, V. N.; Kobayashi, R.; Normand, J.;
Raghavachari, K.; Rendell, A.; Burant, J. C.; Iyengar, S. S.; Tomasi, J.; Cossi, M.;
Rega, N.; Millam, J. M.; Klene, M.; Knox, J. E.; Cross, J. B.; Bakken, V.; Adamo, C.;
Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.;
Pomelli, C.; Ochterski, J. W.; Martin, R. L.; Morokuma, K.; Zakrzewski, V. G.;
Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Dapprich, S.; Daniels, A. D.; Farkas,
Ö.; Foresman, J. B.; Ortiz, J. V.; Cioslowski, J.; Fox, D. J. Gaussian 09, Revision
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pyranose form (Scheme 3).
To conclude, we have efficiently synthesized the proposed
structure of decurrenside D by a chiron approach. Stereoselective
substitution at the anomeric position could build the required fura-
nose structure, and the conversion of the alkyne group to
a-keto
ester group provided the desired intermediate for acetal formation.
A closer analysis of the optical rotation and NMR data indicated a
mismatch of data of the synthesized molecule with that of the nat-
urally isolated. Based on the current results, further synthetic stud-
ies directed to establish the correct molecular structure of
decurreside D (and also the other congeners), are needed.