Synthesis of (+)-goniopypyrone and (+)-goniotriol using Pd-catalyzed carbonylation

Article abstract of DOI:10.1016/j.tetlet.2019.151039

Syntheses of (+)-goniopypyrone and (+)-goniotriol isolated from Goniothalamus giganteus were achieved. The key steps involve Pd-catalyzed carbonylation for lactone ring formation and diastereoselective reduction of ynone using the (R)-CBS catalyst and borane dimethyl sulfide complex.

Full text of DOI:10.1016/j.tetlet.2019.151039

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Synthesis of (+)-goniopypyrone and (+)-goniotriol using Pd-catalyzed carbon-
ylation
Yuki Miyazawa, Makoto Sugimoto, Ayumi Tanaka-Oda, Hidefumi Makabe
PII:
S0040-4039(19)30796-8
DOI:
https://doi.org/10.1016/j.tetlet.2019.151039
TETL 151039
Reference:
Tetrahedron Letters
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Received Date:
Revised Date:
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12 July 2019
7 August 2019
9 August 2019
Please cite this article as: Miyazawa, Y., Sugimoto, M., Tanaka-Oda, A., Makabe, H., Synthesis of (+)-
goniopypyrone and (+)-goniotriol using Pd-catalyzed carbonylation, Tetrahedron Letters (2019), doi: https://
doi.org/10.1016/j.tetlet.2019.151039
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Synthesis of (+)-goniopypyrone and ()-
goniotriol using Pd-catalyzed carbonylation
Yuki Miyazawa, Makoto Sugimoto, Ayumi Tnaka-Oda, Hidefumi Makabe*

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Tetrahedron Letters
journal homepage: www.elsevier.com
Synthesis of (+)-goniopypyrone and ()-goniotriol using Pd-catalyzed carbonylation
Yuki Miyazawaa , Makoto Sugimotoa, Ayumi Tanaka-Odab and Hidefumi Makabea,c
aGraduate School of Science and Technology, Department of Agriculture, Division of Food Science and Biotechnology, Shinshu University, 8304 Minami-
minowa, Kami-ina, Nagano, 399-4598, Japan
bResearch Center for Supports to Advanced Science, Division of Instrumental Research, Shinshu University, 8304 Minami-minowa, Kami-ina, Nagano, 399-
4598, Japan
bInstitute for Biomedical Sciences, Interdisciplinary Cluster for Cutting Edge, Department of Biomolecular Innovation, Shinshu University, 8304 Minami-
minowa, Kami-ina, Nagano, 399-4598, Japan
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
Syntheses of (+)-goniopypyrone and (+)-goniotriol isolated from Goniothalamus giganteus were
achieved. The key steps involve Pd-catalyzed carbonylation for lactone ring formation and
diastereoselective reduction of ynone using the (R)-CBS catalyst and borane dimethyl sulfide
complex.
Available online
2009 Elsevier Ltd. All rights reserved.
Keywords:
natural product
polyketides
styryl lactone
carbonylation
———
 Corresponding author. Tel.: +81-265-77-1630; fax: +81-265-77-1700; e-mail: makabeh@shinshu-u.ac.jp

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Tetrahedron Letters
The trees of Goniothalamus genus, a group of the Annonaceae
Scheme 1B. Synthetic strategy of (+)-goniotriol (2).
family in South East Asia, are known as sources of folk medicines.
McLaughlin and co-workers isolated a number of styryl lactones
from Goniothalamus giganteus including (+)-goniopypyrone and
(+)-goniotriol.1,2 These styryl lactones showed significant
cytotoxicity against 3PS murine lymphocytic leukemia cells.3
Because of their unique structure and significant biological
activities, much effort toward the synthesis of these compounds
has been made.4-11 Shing and co-workers utilized D-glycero-D-
gulo-heptano--lactone as a chiral source. Overall yield of their
synthesis was rather low (> 5%).4,6 Zhou and co-workers
accomplished efficient asymmetric total synthesis of (+)-
goniopypyrone from methyl cinnamate using asymmetric
dihydroxylation and addition of 2-furylcopper in a stereoselective
manner.5 Tsubuki and co-workers employed chiral lactonic
aldehydes prepared from D-isopropyldinedioxy glyceraldehyde.
Their synthesis needed to separate unnecessary diastereomer.7
Surivet and Vatele used mandelic acid as the chiral source. Their
synthesis required the separation of the mixture of different kind
of styryllactones.8 Prasad synthesized these styryl lactones from a
common intermediate. Introduction of the ,-unsaturated double
Scheme 2 and 3 show the synthesis of (+)-goniopypyrone (1)
and 7-epi-goniotriol (3). At the outset, we focused on the
preparation of the key building block 5 from D-()-tartaric acid. D-
()-Tartaric acid was treated with p-TsOH and 2,2-
dimethoxypropane in a mixture of MeOH and dioxane to give
dimethyl ester 9. Treatment of 9 with morpholine afforded diamide
7. Addition of 1.5 eq. of phenylmagnesium bromide furnished -
oxo butylamide 10. Reduction of the keto group of 10 with
NaBH4/CeCl3 afforded a diastereomeric mixture of alcohols in a
20:1 ratio, which after recrystallization gave diastereomerically
pure 11. The absolute configuration of newly formed chiral center
of 11 was confirmed using the advanced Mosher method
(Electronic Supporting information (ESI), Fig. S1).18 Protection of
the
secondary
hydroxyl
group of
11 with
TBSCl
bond required two steps from saturated lactone via syn elimination
in
the
of selenoxide.9,
Yadav and co-worker synthesized 1 using
11
stereoselective Grignard reaction and Grubbs’ ring-closing
metathesis from a common precursor prepared from D-(+)-
mannitol.10
presence of imidazole afforded 6. Addition of ethynylmagnesium
bromide to 6 furnished ynone 12. Reduction of the carbonyl group
of 12 with various reagents is shown in Table 1.
Fig 1. Structures of (+)-goniopypyrone (1) and (+)-goniotriol (2).
The synthetic strategy was shown in Scheme 1. (+)-
Goniopypyrone (1) can be synthesized from 7-epi-goniotriol (3).
The ,-unsaturated -lactone ring of 3 would be constructed
using palladium-catalyzed carbonylation and cyclization of Z-
vinyl iodide 4. The Z-vinyl iodide 4 can be synthesized from iodo
alkyne 5. Compound 5 can be prepared from amide 6. Amide 6 is
prepared from D-()-tartaric acid (Scheme 1A and Scheme 1B).
Scheme 1A. Synthetic strategy of (+)-goniopypyrone (1).

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Scheme 2. Synthesis of cyclization precursor 4.
Table 1. Reduction of the keto group of 12 using various hydride
reagents.
reagent
Conditions
Ratio 13a : 13b
63 : 37
−
Yield %
79
LS-Selectride
9-BBN, (+)-a-pinene
LiAlH4
THF, −20 C, 0.5 h
THF, rt, 13 h
decomp.
decomp.
85
THF, 0 C, 0.5 h
THF, −40 C, 1 h
MeOH, −78 C, 2.5 h
THF, −78 C, 0.5 h
THF, 0 C, 24 h
THF, −20 C, 24 h
−
DIBALH
55 : 45
32 : 68
58 : 42
52 : 48
31 : 69
NaBH4, CeCl3
L-Selectride
88
44
NaBH(OAc)3
80
(S)-CBS (0.2 eq.),
BH3・ DMS (2.0 eq.)
(R)-CBS (0.5 eq.),
BH3・ DMS (1.2 eq.)
88
THF, −30 to −20 C, 1.5 h
88 : 12
78
protected as a benzyl ether afforded 14. Introduction of the iodide
group to 14 using NIS in the presence of AgNO3 furnished 5. The
diimide reaction of
5 using NsNHNH2 and subsequent
deprotection of the acetonide and TBS group under acidic
condition afforded the cyclization precursor 4 (Scheme 2).
With the cyclization precursor 4 to hand, Pd-catalyzed
carbonylation of 4 was performed. As shown in Scheme 3, using
Cl2Pd(PPh3)2 as a catalyst (5 mol%) and Et3N (1.2 eq.) as a base
under a balloon pressure of CO atmosphere at 50oC afforded 16 in
83% yield. Deprotection of the benzyl ether of 16 using TiCl4
afforded 7-epi-goniotriol (3).11 Finally, treatment of 3 with DBU
furnished (+)-goniopypyrone (1) (Scheme 3). The spectral and
physicochemical data of synthetic 1 are in good agreement with
those of the reported values.7
As shown in Table 1, stereoselective reduction of the keto group
was rather difficult. However, using the (S)-CBS catalyst19 and
borane dimethyl sulfide complex gave some stereoselectivity.
Thus, we optimized the reaction conditions to synthesize 13a in a
stereoselective manner (Electronic Supporting information (ESI),
Table. S1). Using 0.5 eq. of the (R)-CBS catalyst and 1.2 eq. of the
borane dimethyl sulfide complex afforded 13a:13b at a ratio of
88:12. The ratio of 13a:13b was determined by isolation yield.
Compound 13a was purified using silica gel column
chromatography. The absolute configuration of the newly formed
chiral center of 13a was confirmed using the advanced Mosher
method (ESI, Fig. S2).18 Undesired 13b was converted to 13a
using the Mitsunobu reaction.20 The hydroxy group of 13a was

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Tetrahedron
In conclusion, (+)-goniopypyrone (1) and (+)-goniotriol (2)
were synthesized through 14 steps in 8.5% and 16 steps in 11%,
respectively. The key reaction was Pd-catalyzed carbonylation to
construct lactone ring. This synthetic strategy should be a useful
for synthesizing other styryl lactones.
Conflict of interest
The authors declare no conflicts of interest.
Acknowledgments
This work was supported by JSPS KAKENHI Grant Number
15K07408
to
H.
M.
We
thank
Edanz
Group
(www.edanzediting.com/ac) for editing a draft of this manuscript.
References and notes
Scheme 3. Synthesis of (+)-goniopypyrone (1).
1.
2.
3.
4.
5.
6.
7.
Fang, X. P.; Anderson, J. E.; Fanwick, P. E.; McLaughlin, J. L. J.
Chem. Soc. Perkin Trans 11990, 1655–1661.
Alkofahi, A.; Ma, W. -W.; Mckenzie, A. T.; Byan, S. R.;
McLaughlin, J. L. J. Nat. Prod. 1989, 52, 1371–1373.
Geran, R. I.; Greenberg, N. H.; MacDonald, M. M.; Shumacher,
A. M.; Abbott, B. J. Cancer Chemother. Rep. 1972, 3, 103.
Shing, T. K. M.; Tsui, H. –C.; Zhou, Z. –H. Tetrahedron Lett.
1993, 34, 691–692.
Zhou, W. S.; Yang, Z. –C. Tetrahedron Lett. 1993, 34, 7075–
7076.
Shing, T. K. M.; Tsui, H. –C.; Zhou, Z. –H. J. Org. Chem. 1995,
60, 3121–3130.
Tsubuki, M.; Kanai, K.; Nagase, H.; Honda, T. Tetrahedron 1999,
55, 2493-2514.
8.
9.
Surivet, J. –P.; Vatèle J. –M. Tetrahedron 1999, 55, 13011-13028.
Prasad, K. R.; Dhaware, M. G. Synthesis 2007, 3697-3705.
10. Yadav, V. K.; Agrawal, D. Chem. Commun. 2007, 5232-5234.
11. Prasad, K. R.; Gholap, S. L. J. Org. Chem. 2008, 73, 2-11.
12. Miyazawa, Y.; Hattori, Y.; Makabe, H. Tetrahedron Lett. 2018,
59, 4024-4027.
13. Negishi, E.; Makabe, H. Handbook of Organopalladium
Chemistry for Organic Synthesis, John Wiley & Sons: New York,
2002, Vol. 2, pp 2455-2471.
14. Negishi, E.; Copéret, C.; Ma, S.; Liou, S. Y.; Liu, F. Chem. Rev.
1996, 96, 365-393.
Scheme 4. Synthesis of (+)-goniotriol (2).
15. Makabe, H.; Okajima, M.; Konno, H.; Kamo, T.; Hirota, M.
Biosci. Biotechnol. Biochem. 2003, 67, 2658-2660.
16. Kurogome, Y.; Hattori, Y.; Makabe, H. Tetrahedron Lett. 2014,
55, 2822-2824.
17. Hikosaka, G.; Hattori, Y.; Makabe H. Tetrahedron: Asymmetry
2014, 25, 1367-1371.
18. Ohtani, I.; Kusumi, T.; Kashman, Y.; Kakisawa, H. J. Am. Chem.
Soc. 1991, 113, 4092-4096.
19. Corey, E. J.; Bakshi, R. K.; Shibata, S. J. Am. Chem. Soc. 1987,
109, 5551-5553.
Synthesis of (+)-goniotriol (2) utilizing similar Pd-catalyzed
carbonylation as the key step is as follows (Scheme 4). Treatment
of 14 with TBAF afforded alcohol 16. Mitsunobu reaction of the
secondary hydroxyl group of 16 furnished 17 with a yield of 91 %
yield. Introduction of the iodide group of 17 using NIS in the
presence of AgNO3 furnished 18. The diimide reaction of 18 using
NsNHNH2 and subsequent deprotection of the acetonide group
under acidic condition afforded cyclization precursor 8. Pd-
catalyzed carbonylation of 8 afforded 20 in high yield.
Deprotection of the benzyl ether of 20 using TiCl4 afforded (+)-
goniotriol (2) (Scheme 4). The spectral and physicochemical data
of synthetic 2 are in good agreement with those of the reported
values.11
20. Mitsunobu, O. Synthesis 1981, 1-28.
Supplementary Material
Supplementary data associated with this article can be found, in
the online version at doi:

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Synthesis of (+)-goniopypyrone and ()-goniotriol
was accomplished.
The lactone ring was constructed using Pd-
catalyzed carbonylation.
Diastereoselective reduction of ynone was
accomplished using (R)-CBS catalyst.