Kara George Rosenker_8 October 2011

Transcription

Total Synthesis of (+)-Decursivine
Sun, D.; Zhao, Q.; Li, C. Org. Lett. 2011, ASAP.
DOI: 10.1021/ol2021669
O
O
N Boc
CO2Me
HO
O
O
O
PIFA;
then TFA
60%
O
O
H
O
H
N
CO2Me
H
H
N
H
O
O
N
H
-CO2Me
O
H
N
H
N
H
(+)-decursivine
Kara George Rosenker
Wipf Group Current Literature
8 October 2011
Kara George @ Wipf Group
Page 1 of 14
12/28/2011
(+)-Decursivine: Isolation and Biological Activity
HO
O
O
O
H
MeO
H
N
O
H
H
N
H
H
O
O
N
H
N
H
(±)-serotobenine
(+)-decursivine
!
!
!
!
(+)-Decursivine was isolated in 2002 from the leaves and stems of Rhaphidophora
decursiva, a perenial, evergreen vine found in the Cuc Phuong National Park in Vietnam
(+)-Decursivine exhibits moderate antimalarial activity against the chloroquinineresistant Plasmodium falciparum (IC50 = 4.4 µg/mL)
Structurally similar (±)-serotobenine was also isolated from the leaf extract; however, it
showed no activity against Plasmodium falciparum
Synthetic challenges include the sensitivity of the electron-rich indole to oxidation, the
construction of the stereogenic centers on the dihydrobenzofuran, and the formation
of the eight-membered lactam
Zhang, H.; Qiu, S.; Tamez, P.; Tan, G. T.; Aydogmus, Z.; Hung, N. V.; Cuong, N. M.;
Angerhofer, C.; Soejarto, D. D.; Pezzuto, J. M.; Fong, H. H. S. Pharm. Biol. 2002, 40, 221-224.
Leduc, A. B.; Kerr, M. A. Eur. J. Org. Chem. 2007, 237-240.
Mascal, M.; Modes, K. V.; Durmus, A. Angew. Chem. Int. Ed. 2011, 50, 4445-4446.
Qin, H.; Xu, Z.; Cui, Y.; Jia, Y. Angew. Chem. Int. Ed. 2011, 50, 4447-4449.
Page 2 of 14
12/28/2011
Biosynthesis of (±)-Serotobenine & (+)-Decursivine
O
O
O
O
O
O
H
H
N
H
NH
O
HO
N
H
N
H
!
!
(+)-decursivine
The biosynthesis of both (+)-decursivine and (±)-serotobenine likely involves the
cyclization of a cinnamide composed of serotonin and an appropriately substituted
cinnamic acid
This is supported by the co-isolation of moschamine, moschaminindolol, and
serotobenine
HO
HO
HO
O
MeO
MeO
O
H
NH
MeO
H
N
HO
HO
HO
N
H
moschamine
O
H
H
N
H
O
N
H
moschaminindolol
N
H
(±)-serotobenine
Sato, H.; Kawagishi, H; Nishimura, T.; Yoneyama, S.; Yoshimoto, Y.; Sakamura, S.; Furusaki, A.; Katsuragi, S.; Matsumoto, T. Agric. Biol. Chem. 1985, 49, 2969-2974.
Sakamura, S.; Terayama, Y.; Kawakatsu, S.; Ichihara, A.; Saito, H. Agric. Biol. Chem. 1978, 42, 1805-1806.
Sakamura, S.; Terayama, Y.; Kawakatsu, S.; Ichihara, A.; Saito, H. Agric. Biol. Chem. 1980, 44, 2951-2954.
Page 3 of 14
12/28/2011
First Total Synthesis of (±)-Decursivine
amide
formation
O
O
O
H
O
O
O
O
H
N
H
H
O
H
OH
(±)-decursivine
two carbon
homologation
OH
etherification
Diels-Alder/
Plieninger Indolization
CO2Me
HO
PivO
O
N
H
aldol
N
Ts
N
Ts
CO2Me
PivO
O
N
Ts
NH2
O
CHO
Reported by Kerr and co-workers in 2007
Key Feature: Diels-Alder/Plieninger indolization
Page 4 of 14
12/28/2011
First Total Synthesis of (±)-Decursivine
OH
1. TsCl, pyr.
2. NaIO4/SiO2
(82%, 2 steps)
O
NH2
1. NaClO2, NaH2PO4
2. TMSCHN2
3. (Chx)2BI, Et3N
piperonal
(68%, 3 steps)
1. sealed tube;
then DBU (95%)
2. PivCl, Et3N (94%)
OPiv
3. TsCl, Et3N (84%)
4. NaBH4, SiO2 (78%)
CHO
PivO
N
Ts
NHTs
NTs
O
O
O
1. DMP (83%) O
2. oxone
OH 3. TMSCHN
2
(80%, 2 steps)
O
O
CO2Me
DIBAL (70%)
HO
PivO
H
H
H
H CO2Me
O
O
N
Ts
N
Ts
N
Ts
1. Mg0, NH4Cl (83%)
O (67%)
2. TFA,
N+ N
O
1. OsO4, NMO
2. NaIO4
3. H2SO4
(84%, 3 steps)
O
O
O
Zn0,
H
H CO2Me
NO2
1.
HCl
2. pyr., µW
3. Mg0, NH4Cl
O
(43%, 3 steps)
N
Ts
O
O
H
H
N
H
O
(±)-decursivine
N
H
20 Steps, 2.5% overall yield
Page 5 of 14
12/28/2011
Expedient Syntheses of (±)-Decursivine
O
Br
2 steps
O
NH2
O
O
OH
Cl Cl
O
O
O
H
N
HO
N
H
O
HO
h!
Cl Cl
N
H
O
O
O
O
O
Cl
O
H
N
O
O
H
N
O
H
H
N
H
O
HO
HO
N
H
N
H
N
H
(±)-decursivine
Key Step: Witkop photocylcization/elimination/O-Michael addition
Mascal and co-workers: 4 steps, 53% overall yield
Jia and co-workers: 4 steps, 20% overall yield
Mascal, M.; Modes, K. V.; Durmus, A. Angew. Chem. Int. Ed. 2011, 50, 4445-4446.
Qin, H.; Xu, Z.; Cui, Y.; Jia, Y. Angew. Chem. Int. Ed. 2011, 50, 4447-4449.
Page 6 of 14
12/28/2011
Title Paper: Synthetic Design of (+)-Decursivine
O
O
O
O
O
O
N
R2
O
H
[O]
R2
N
CO2Me
H
CO2Me
HO
O
O
H
H
N
H
O
O
N
R1
removal of
1
R , R2, and CO2Me
N
R1
N
H
(+)-decursivine
Strategy includes:
! Biomimetic stereoselective oxidative intramolecular [3+2]
cycloaddition
! Chirality transfer from the tryptophan to the two newly formed
chiral centers
Sun, D.; Zhao, Q.; Li, C. Org. Lett. 2011, ASAP. DOI: 10.1021/ol2021669
Page 7 of 14
12/28/2011
Oxidative Dimerization of Substituted P-Hydroxystyrenes
B
R1
[O]
O
R2
R2
R2
R2
R1
R1
O
O
O
OH
R1
H
R1
R1
R1
R1
R2
O
OH
R2
R2
OH
R2
[O]: PhI(OAc)2, Ag2O, K3[Fe(CN)6], or HRP/H2O2
H
N
R1
R1
O
R1
OR2
OH
HN
N
H
N
H
O
O
O
OMe
R2
R2
fragnasols A-C &
dehydrodiisoeugenol
O
R3
ephedradine A-D &
O-methylorantine
OR2
R1
OMe
R1O
CO2R2
2C
OH
O
OH
OH
schizotenuins 1-3
Juhász, L.; Kürti, L.; Antus, S. J. Nat. Prod. 2000, 63, 866-870.
Maeda, S.; Masuda, H.; Tokoroyama, T. Chem. Pharm. Bull. 1994, 42, 2500-2505.
Wasserman, H. H.; Brunner, R. K.; Buynak, J. D.; Carter, C. G.; Oku, T.; Robinson, R. P. J. Am. Chem. Soc. 1985, 107, 519-521.
Page 8 of 14
12/28/2011
Oxidative [3+2] Cycloaddition: Phenols and Electron-Rich Alkenes
R
R1
OH
[O]
R
B
R
R1
O
R1
H
R
R1
R
R
R
R
O
O
[O]: PIFA, PhI(OAc)2, or HRP/H2O2
N CO2Me
HO
OH
N
CO2Me
OH
PIFA (25%)
N
H
N
CO2Me
CO2Me
O
CO2Me
N
O
N
O
N
H
N
CO2Me
CO2Me
MeO
N
OMe CO2Me
truncated
haplophytine
Nicolaou, K. C.; Majumder, U.; Roche, S. P.; Chen, D. Y.-K. Angew. Chem. Int. Ed. 2007, 46, 4715-4718.
Page 9 of 14
12/28/2011
Intramolecular Oxidative [3+2] Cycloaddition: Diazonamide A
R
R1
OH
[O]
R
B
R
R1
O
H
R1
R
R
R1
R
R
R
O
O
[O]: PIFA, PhI(OAc)2, or HRP/H2O2
O
ArO2SHN
N
H
N
HN
N
CO2Me
O
PhI(OAc)2
LiOAc
ArO2SHN
O
CO2Me
O
N
HN
ArO2SHN
O
O
CO2Me
HO
N
H
N
H
O
Br
Ar = 2-nitrophenyl
Br
O
(20-25%)
(-)-Diazonamide A
(7-8%)
N
N
ArO2SHN
N
H H
Br
CO2Me
O
O
N
H
O
Burgett, A. W. G.; Li, Q.; Wei, Q.; Harran, P. G. Angew. Chem. Int. Ed. 2003, 42, 4961-4966.
Page 10 of 14
Br
(15%, 1:1)
12/28/2011
Title Paper: Optimization of the [3+2] Cycloaddition
O
O
O
O
N
R2
O
PIFA, rt, 4 h
1
R2
N
CO2Me
H
CO2Me
HO
O
H
O
N
R1
2
N
R1
entrya
1
R1
R2
solvent
2
yield (%)b
1
1a
H
H
TFE
2a
0
2
1b
CO2Bn
H
TFE
2b
0
3
1c
H
Bn
TFE
2c
0
4
1d
Bn
Bn
TFE
2d
0
5
1e
Ts
Bn
TFE
2e
20
6
1f
CO2Bn
Bn
TFE
2f
24
7
1f
CO2Bn
Bn
HFIP
2f
41
8c
1f
CO2Bn
Bn
HFIP
2f
66
a
Reaction conditions: 1 (0.05 mmol), PIFA (0.06 mmol), TFE or HFIP
(1 mL), rt, 4 h. b Isolated yield based on 1. c 5 mL of HFIP were used.
- Changing the oxidant to PhI(OAc)2 led to a decrease in product yield.
- Increased and decreased reaction temperatures did not improve the product yield.
Page 11 of 14
12/28/2011
NHCO2Me
CO2Me
CO2Me
65%
N
H
95%
1. TBDPSCl, im.
2. NaI, TMSCl
TBDPSO
73%
N
H
O
EDC/DMAP
3,4-(methylenedioxy)
cinnamic acid
NH2
NHCO2Me
1. Pb(OAc)4
TFA
2. Zn
HO
O
O
NH
1. Boc2O
Et3N, DMAP
2. TBAF
CO2Me
TBDPSO
83%
N
H
O
CO2Me
N
H
O
O
N Boc
CO2Me
HO
PIFA, K2CO3,
HFIP, rt, 6 h;
43%
N
Boc
O
O
O
H
Boc
CO2Me
N
H
O
N
Boc
Page 12 of 14
12/28/2011
O
O
O
O
O
N Boc
CO2Me
HO
PIFA/HFIP, rt, 6 h;
then TFA, rt, 24 h
O
H
1. LiOH
CO2Me 2. i-BuOCOCl, PhSeNa
3. Bu3SnH/AIBN
H
N
H
O
60%
75%
N
H
N
Boc
O
O
O
H
H
N
10 steps, 16.7% overall yield
H
O
N
H
(+)-decursivine
Page 13 of 14
12/28/2011
Conclusion
! Li and co-workers accomplished the first asymmetric synthesis of (+)decursivine in 10 steps and a 16.7% overall yield
! Key features of their synthesis include:
! PIFA-mediated oxidative intramolecular [3+2] cycloaddition of 5hydroxytryptophans with substituted cinnamamides in a highly
diasteroselective manner
! Traceless chirality transfer from the starting tryptophan to the target
molecule
! Application of this oxidative intramolecular [3+2] cycloaddition
provides an additional methodology for accessing dihydrobenzofurans
Page 14 of 14
12/28/2011

Kara George Rosenker_8 October 2011

Transcription

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