Beruflich Dokumente
Kultur Dokumente
Baran Lab
ALKALOID PHOTOCHEMISTRY
(for a nice review of photochemistry of alkaloids prior to 1980 see Singh, A.
P.; Stenberg, V. I.; Parmar, S. S. Chem. Rev. 1980, 80, 269-282)
K. J. Eastman
The following scheme represents a likely pathway for the observed products
(see Santamaria, J. Pure & Appl. Chem., 1995, 67, 141-147).
I. Introduction:
[O]
-H
Py
Py
H2O 2
H2O 2
Py
KCN
CN
O2H
Py
N
H
Py
Py
The survey to follow will primarily features nitrogen as the key participant for
both sensitized and direct photochemically induced reactions.
H2O2
CONH2
O
Py
Py
Py
H
N
N+
H
O
sens/h
/O2/KCN
CN
N
CONH2
H2O 2
H
N
Py
N
H
Py
N
CH2 CN
Py
N
CH2CONH2
H
N
sens/h /O2/KCN
Py
Hubert-Brierre and co-workers also investigated the irradiation of N-methylanabasine under a similar set of conditions.
CONH2
Alkaloid Photochemistry
Baran Lab
H 2O-KOH
K. J. Eastman
Thirteen years after thier first observations with the pyridinium salt
photocyclization process, Mariano and co-workers returned to this area and have
subsequently reported on several occasions their investigations into the potential
synthetic power of a tandem sequences involving:
(1) photoinduced cyclization of pyridinium cations
(2) stereocontrolled nucleophile addition to produce bicyclic aziridines, and
(3) stereocontrolled nucleophilic cleavage of the bicyclic aziridine to produce
highly functionalized aminocyclopentenes.
(Ling, R.; Yoshida, M.; Mariano, P. S. J. Org. Chem. 1996, 61, 4439-4449, Song, L.;
Duesler, E. D.; Mariano, P. S. J. Org. Chem. 2004, 69, 7284-7293).
X-
R1
1. h
HNu 1
N+
OH
R1
H
2. base
R2
Nu1
R2
NHR1
1. h
HNu1
Nu2
2. base
R2
Mariano (1983):
OCH3
CH2CH=C(CH3 )2
ClO4- N+
CH2CH=CH2
CH3OH
ClO4- N+
Nu1
CH2CH=CH2
CH3OH
OCH3
HClO4
CH3OH
Bn
Bn
h or
CN
CN
NHCH2 CH=CH2
H3CO
EWG
EWG
head-to-head adducts
OCH3
Alkaloid Photochemistry
Baran Lab
+ RCOOH
H3CO
H3 CO
N
H3CO
h
-CO2
K. J. Eastman
H3CO
N
H3 CO
h /O 2
10-20 %
R
H3CO
Bick and co-workers reported the photo-oxidative cleavage of some benzylisoquinoline-based alkaloids (Bick, I. R. C.; Bremner, J. B.; Wiriyachitra, P.
Tet. Lett. 1971, 50, 4795-4797).
laudanosine:
H3CO
H3CO
N
H3CO
h /O2
H3CO
HO -
H3CO
CHO
NaBH4
H3 CO
H3 CO
H3 CO
H3 CO
N+
I-
h
/ROH
H3 CO
H3 CO
OCH3
XN+
H3 CO
h
/ROH
H3CO
H3CO
H3 CO
OCH3
OCH3
10 %
H3CO
H3 CO
H3CO
H3CO
OCH3
O
H3CO
OCH3
H3CO
85 %
H3 CO
H3 CO
H3CO
N+
H3CO
N
OR
h
/ROH
H3 CO
N
H3 CO
R
H3 CO
H3 CO
H3 CO
Alkaloid Photochemistry
Baran Lab
H3CO
N
H3 CO
h
/O2
H3CO
O
O
RCOOH
OCH3
OCH3
H3 CO
OHC
N
O
NaBH4
H3 CO
V. Tropane alkaloids:
OCH3
H3CO
OCH3
H3CO
K. J. Eastman
sens/h
/O2
HO
O
OCH3
H3CO
OH
OH
OCH3
OH
OCH3
OH
O
H
h
O
N
OH
OCH3
h
/MeOH/no O2
O
O
OCH3
OH
H
Alkaloid Photochemistry
Baran Lab
K. J. Eastman
H3 CO
OCH3
h, 366 nm
H3 CO
OCH3
OCH3
OH
R
O
H3CO
-
OH
OH
R
-
85 %
O
N
H3CO
OH
N+
H3CO
R
O
CH2R
OH
H3 CO
H3 CO
N
H3CO
H3CO+
H3CO+
reduction
H3CO
Cl-
H3CO
HO
HO
N
H
sens/h /O 2
N
N
H3CO
OCH3
Alkaloid Photochemistry
Baran Lab
Enamide photochemistry is well known and its useful application has been
thoroughly investigated. Simple enamides generally undergo a [1,3]-acyl radical
shift to afford vinylogous amides. Below are examples of the photorearrangement
of 1-acylindoles to 3 acylindolenines (Ban, Y.; Yoshida, K.; Goto, J.; Oishi, T. J. Am.
Chem. Soc. 1981, 103, 6990-6992).
O
ClN+
sens/h /O2
Cl-
N+
N
K. J. Eastman
H3COC
COCH3
H3COC
O
Cl-
N
N
N
H
COCH3
O
alkyl
20 %
H3 CO
O
N
N
H
sens/h
H3 CO
N
H
CO2CH3
H3 CO
alkyl
O
N
unstable!
CO2 CH3
N
HO
NH2
N
H
CO2CH3
NH
O
80 %
N
O
O
sens/h
H3CO
H3 CO
N
N
H
N
H
H
N
OH
Alkaloid Photochemistry
Baran Lab
Sinibaldi and co-workers have demonstrated the the feasibility for a photochemical approach to 3,3-spiro indolines (Ibrahim-Ouali, M.; Sinibaldi, M. E.;
Troin, Y., Cuer, A.; Dauphin, G.; Gramain, J-C. Heterocycles 1995, 41, 1939-1950).
O
h
N
CH2OBn
Ph
N
Ph
O
O
CH2OBn
25 %
N+
NH
RO
RO
a) h
b) SET
ClO4 -
ClO4N
HN
TMS
-TMS
I2
67 %
H
N
RO
RO
Coyle and co-workers have shown the irradiaton of Mannich bases obtained from
phthalimides, formaldehyde and 1,2,3,4-tetrahydroisoquinolines carrying methoxy
substituents gives pentacyclic photoproducts (Coyle, J. D.; Bryant, L. R. B.; Cragg,
J. E. J. Chem. Soc. Perkin Tans. I 1985, 1177-1180).
38 %
Ph
HN
TMS
CH2 OBn
K. J. Eastman
N
N
O
H
N
6%
18 %
OCH3
HCl
28 %
OH
OCH3
OCH3
H3 CO
H3 CO
N
N
25 %
HO
N+
H3CO
7%
Alkaloid Photochemistry
Baran Lab
H3CO
N
H3CO
H3 CO
StBu
tBuS
H3CO
H3CO
OH
* H C
OH
OH
StBu
OTMS
h
N
O
N H
RO2 C
H3 CO
HO
OH
CHO
CO2R
H
H
CO2R
CO2R
HO H
O
H
MeOOC
H3 CO
StBu
H3 CO
K. J. Eastman
H
C
C
H
OH
N
TMSO
MeOOC
OHC
HO
O
COOMe
O
N
OTMS
HO
O
O