Synthesis of a peptide-linked chlorin dyad as a model compound for the photosynthetic reaction centre

Article abstract of DOI:10.1002/chem.200700222

The enantiomerically pure chlorins 19 and 21 were synthesised from tripyrrolic nickel complex rac-17 and pyrrole building blocks 12 and 16. The pyrroles are annelated with norbornane moieties which contain the chiral information as well as two different f

Full text of DOI:10.1002/chem.200700222

FULL PAPER
DOI: 10.1002/chem.200700222
Synthesis of a Peptide-Linked Chlorin Dyad as a Model Compound for the
Photosynthetic Reaction Centre
Thorsten Kçnekamp,[a] Anna Ruiz,[a] Jçrn Duwenhorst,[a, b] Wolfgang Schmidt,[a]
[a]
Tobias Borrmann,[a] Wolf-DieterStohre,r
and Franz-Peter Montforts*[a]
Dedicated to Professor Gerhard Quinkert on the occasion of his 80th birthday
Abstract: The enantiomerically pure
chlorins 19 and 21 were synthesised
from tripyrrolic nickel complex rac-17
and pyrrole building blocks 12 and 16.
The pyrroles are annelated with nor-
bornane moieties which contain the
chiral information as well as two differ-
ent functionalities. The functional
groups, namely a carboxylic acid ester
and a carbonitrile group, of chlorin 21
finally allowed the formation of an
amino acid functionality at the periph-
ery of the macrotetracycle. By using
principles of peptide chemistry, the two
chlorin subunits were joined to form
the peptide-linked chlorin–chlorin dyad
24, which mimics the molecular parts
of the natural photosynthetic reaction
centre.
Keywords: chlorin · dyes/pigments ·
peptide linkages · photosynthesis ·
porphyrinoids
Introduction
The elementary step of photosynthesis in bacteria and
plants is the light-induced electron transfer from the special
pair of (bacterio)chlorophylls a (1) and b along a chain of
further (bacterio)chlorophyll pigments to quinone acceptors,
in which the electrons are first stored in a hydroquinone
structure.[1] Knowledge of the structures of naturally occur-
ring photosynthetic reaction centres originates from crystal-
structure investigations.[2] The first investigations into the
bacterial photosynthetic reaction centres not only elucidated
the spacial arrangement of pigments (Figure 1) but also that
of the membrane proteins to which the bacteriochlorophylls
are anchored by lipophilic interactions.[3]
Numerous artificial-photosynthesis model systems were
designed to study the factors influencing the light-induced
electron-transfer reaction that is the key photosynthesis
step.[4] The majority of model systems so far consist of por-
phyrin subunits,[4,5] which have different photophysical prop-
erties to the “natural” chlorin chromophore 2. There are,
however, a few exceptions which make use of pigments de-
[a] Dipl.-Chem. T. Kçnekamp, Dr. A. Ruiz, Dr. J. Duwenhorst,
Dr. W. Schmidt, Dr. T. Borrmann, Prof. Dr. W.-D. Stohrer,
Prof. Dr. F.-P. Montforts
Institut für Organische Chemie
Universität Bremen
Leobener Strasse NW2/C, 28359 Bremen (Germany)
Fax : (+49)421-218-3720
E-mail: mont@chemie.uni-bremen.de
rived from naturally occurring chlorophyll a (1).[6]
.
To obtain photosynthesis models based on chlorin pig-
ments which mimic the spacial arrangement of naturally oc-
curring systems, we aimed to synthesise the enantiomerically
pure chlorin 7 (Scheme 1). The carboxylic acid group and
[b] Dr. J. Duwenhorst
Elastogran GmbH, KFE
Landwehrweg, Postfach 1140, 49448 Lemfçrde (Germany)
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flexibility and selectivity due to the application of four dis-
tinct building blocks, 3–6, which can be structurally modified
with respect to the envisaged substitution pattern of the
target chlorin.
Results and Discussion
An intermediate in previous syntheses of chlorins and cor-
rins, the tricyclic nickel complex rac-17 (see Scheme 4), is
also useful for the synthesis of the desired chlorin intermedi-
ates 19 and 21. The nickel complex rac-17 was synthesised
previously from the pyrrolic building blocks 3, 4 and 6.[7a,b]
To achieve a chlorin structure such as 7, a new enantio-
meric D-ring building block was required for the synthetic
route. Pyrroles attached to chiral norbornane moieties with
carboxylic acid functions were prepared in our laboratory
from a,b-unsaturated sulfone derivatives[9] according to
Schçllkopfꢁs isocyanide method[10] for the construction of
heterocyclic ring systems. The a,b-unsaturated sulfone start-
ing compound for the pyrrole synthesis was obtained from
the sulfone lactone carboxamide 8.[9a] Carboxamide 8 was
prepared from norbornene dicarboxylic acid[11] in 100%
enantiopurity, which is preserved during the whole synthetic
sequence. During the course of the present synthetic studies,
we found that the enantiomerically pure tricyclic lactone
carboxamide 8 could be treat-
Figure 1. Schematic representation of the spacial arrangement of the pig-
ments in the bacterial photosynthetic reaction centre of Rhodopseudomo-
nas viridis.[2] BChl: bacteriochlorophyll; BPheo: bacteriopheophytin.
ed directly with isocyanides to
yield the pyrrole intermediate
9 (Scheme 2).
The reaction of
8
with
benzyl isocyanoacetate under
basic reaction conditions first
yields the a,b-unsaturated sul-
fone function desired for pyr-
role-ring formation with the
isocyanide. The pyrrole 9 was
further functionalised by Vils-
meier formylation at the free
a-position to form pyrrole 10.
Under the reaction conditions
of the formylation process, the
carboxamide group at the nor-
bornane periphery was also
transformed into a cyano func-
tion, which is thus ready for
Scheme 1. Synthetic concept for the construction of chlorin subunit 7 from monocyclic building blocks 3–7.
the amino function of 7 should allow covalent linkages, simi-
lar to those in peptides, between the chlorin subunits, there-
by forming oligomers or chlorin acceptor systems. The con-
formation of the peptide-like backbone could lead to similar
orientations of the pigments to those found in the protein–
pigment interactions of the natural systems.
Enantiomerically pure subunits are required to obtain ste-
reochemically homogenous oligomeric systems. It should be
possible to construct the target chlorin subunit 7 according
to the concept we developed for the total synthesis of chlor-
ins[7] and corrins.[8] The merits of this concept are the high
the reduction reaction planned for the very end of the
whole synthetic sequence.
From the pyrrole aldehyde 10, two routes were followed
to produce the slightly different D-ring building blocks 12
and 16 (Scheme 3). On the more direct path, the a-benzyl
ester function of 10 was cleaved by hydrogenation and this
was followed by decarboxylative bromination to yield the
bromopyrrole aldehyde 12. With the aldehyde function and
the bromo substituent, building block 12 is ready to be in-
troduced into the synthetic scheme that leads to chlorin
19.[7c] At first glance, this reaction sequence looks very at-
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Photosynthesis Model Compound
FULL PAPER
Synthesis of chlorin subunits:
With the D-ring building
blocks 12 and 16 at hand, the
target chlorins 19 and 21 could
be synthesised. After hydroly-
sis of the ester group in rac-17,
the pyrrole aldehydes 12 or 16
were linked in the presence of
acid to the tricycle by decar-
boxylation and decomplexation
Scheme 2. a) 1) CNCH2CO2Bn, THF, tBuOK, RT, 1 h; 2) THF, CH2N2/diethyl ether, 73%; b) DMF, POCl3,
808C, 2 h, 60%.
(Scheme 4). Recomplexation
of the resulting linear tetrapyr-
rolic macrocycles with zinc(II)
acetate gave the metal com-
plexes 18 and 20. The zinc sta-
bilises the quite sensitive mac-
rocycles and exercises a tem-
plate effect in the final cyclisa-
tion process.
Both metal complexes 18
and 20 were obtained as a ter-
nary mixture of enantiomeri-
cally pure diastereomers on ac-
count of the chiral centres at
the C21 atoms and because of
the helicity of the tetrapyrrolic
chromophore. Due to these
stereochemical features, we did
not carry out full characterisa-
tions of the linear tetrapyrroles
18 and 20. In the case of the
zinc complex 18, cyclisation
was initiated by base-induced
elimination of HCN from C21
Scheme 3. a) Pd/C, H2, THF/NEt3, RT, 30 min, 100%; b) pyridinium perbromide, pyridine, CH2Cl2, room tem-
perature, 18 h, 45%; c) 1) NaOAc, HONH2·HCl, MeOH, RT, 30 min; 2) carbonyl diimidazole, CHCl3, RT,
16 h, 84%; d) THF, HOAc, Pd/C, H2, RT, 2 h, 100%; e) 1) THF, SOCl2, 508C, 2 h; 2. THF, Li 9-BBNH,
À808C, 30 min, 60%; f) THF, H2O, HOAc, CAN, room temperature, 2 h, 77%. CAN: ceric ammonium ni-
trate; Li 9-BBNH: lithium 9-borobicycloACHTRE[UNG 3.3.1]nonane hydride.
and this was followed by
attack of the resulting enamine
tractive, but the yield of 45% after the bromination step is
rather low and unfortunately not very reproducible.
structure on C5. The formation of the target chlorin 19 was
completed by HBr elimination. The zinc complex 20 cyclised
on heating in trichlorobenzene to yield the desired chlorin
21. Here, enamine formation is also initiated by HCN elimi-
nation from C21 and the cyclisation process is completed by
loss of HCN from C5. The two chlorins differ from each
other constitutionally in the positions of the cyano and me-
thoxycarbonyl groups and stereochemically by the configu-
ration of the bridge-head atoms of the norbornane moieties.
The stereochemical difference is reflected in opposite
Cotton effects in the CD spectra of 19 and 21. As chlorin 21
could be synthesised with higher reliability, it was chosen for
continuation of the synthetic pathway.
Therefore, we envisaged an alternative route that leads to
the D-ring building block 16 in a similar yield but with high
reproducibility. The formyl function was transformed
through oxime formation into an a-cyano group and this
was followed by debenzylation to yield the carboxylic acid
derivative 14. As expected, a direct decarboxylative Vilsmei-
er formylation of 14 failed, due to deactivation of the pyr-
role ring by the electron-withdrawing cyano substituent.
To achieve the goal, the carboxylic acid chloride was pre-
pared and reduced with lithium 9-BBN hydride at low tem-
perature to produce alcohol 15. CAN oxidation of the alco-
hol function yielded the D-ring building block 16 with the
formyl and cyano functionalities necessary for completion of
the synthesis of chlorin macrotetracycle 20. This protocol
for the transformation of a pyrrolic a-carboxylic acid group
into an a-hydroxymethyl or a-formyl function could be of
general interest for pyrrole and tetrapyrrole chemistry be-
cause these functions are generally used for linking pyrrole
units together.
Synthesis of a chlorin dyad: Chlorins 21 and 19 represent
masked amino acid units, which could be transformed into
amino acids by ester hydrolysis and by reduction of the
cyano functions into aminomethyl groups.
The ester function of 21 was hydrolysed with potassium
hydroxide under the usual reaction conditions (Scheme 5).
The activation of the carboxylic acid group was best ach-
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F.-P. Montforts et al.
Scheme 4. a) 1. KOH, MeOH/H2O 9:1, THF, reflux, 45 min; 2) 12, CHCl3, pTsOH, reflux, 20 min; 3) CH2Cl2, Zn
52%; b) DBU, Zn(OAc)2, sulfolane, 608C, 2 h, 40%; c) 1) KOH, MeOH/H2O 9:1, THF, 708C, 30 min; 2) 16, CHCl3, pTsOH, reflux, 30 min; 3) CH2Cl2,
Zn(OAc)2/NaOAc, MeOH, RT, 40 min, 59%; d) 1,2,4-trichlorobenzene, 2108C, 40 min, 42%. DBU: 1,8-diazabicyclo[5.4.0]undec-7-ene; pTsOH: para-
toluenesulfonic acid.
ACHTREU(NG OAc)2/NaOAc, MeOH, RT, 20 min,
ACHTREUNG
A
ACHTREUNG
Scheme 5. a) 1) 21, KOH, MeOH/H2O 9:1, THF, 608C, 40 min; 2) DCC, NHS, CH2Cl2, RT, 90 min, 63%; b) 1) 21, CoCl2·6H2O/NaBH4, THF/H2O, 0 8C,
20 min, then RT, 2 h; 2) NH3, 15 min, 60–80%; c) 22+23, DMAP, THF, RT, 3 h, 76%. DCC: N,N’-dicyclohexylcarbodiimide; DMAP: 4-dimethylamino-
pyridine; NHS: N-hydroxysuccinimide.
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Photosynthesis Model Compound
ieved by the N-hydroxy
FULL PAPER
succinACHTREUNGimide derivative 22.
Other activation reagents,
such as iso-butyl chlorofor-
mate, did not work because
the nucleophilic amino com-
ponent reacted at the carbon-
yl function of the activation
group and not at the activat-
ed but sterically hindered car-
boxyl group itself. The unde-
sired reaction was established
to have occurred by isolation
of the corresponding carba-
mate derivative of amino
component 23.
The cyano group of chlorin
21 represents an ideal case of
a protected amino function.
Selective reduction of the
cyano group with sodium
borohydride/cobalt chloride
transformed chlorin 21 into
its amino derivative 23,[12]
which was thus ready for
peptide coupling with the ac-
tivated ester 22. The actual
reduction agent is a suspend-
ed heterogenous cobalt hy-
drido compound which is
formed in situ from sodium
borohydride and the cobalt salt.
Figure 2. Two different views of stick drawings for each of the PM3-calculated preferred conformations A–C
of dyad 24. (Hydrogen atoms are omitted for clarity.)
thetic reaction centre (Figure 1), a semiempirical PM3 calcu-
Conformation of dyad 24: The structure of chlorin–chlorin
dyad 24 was confirmed by its spectroscopic properties. ESI
mass spectrometry (positive and negative) showed a molecu-
lar mass of 1186 and, with high-resolution conditions, a mo-
lation gave three energetically favoured conformations.
Conformation B is lowest in energy and shows a perpen-
dicular arrangement of the two chlorin subunits, which
therefore should not show orbital interactions. This is indi-
cated by the UV/visible spectrum as well as by NOE meas-
urements on 24 and is confirmed by the PM3 calculation.
Interestingly, a similar arrangement of two chlorin subu-
nits was found by PM3 modelling of covalently unlinked
chlorins. It can be supposed that this particular arrangement
originates in Coulomb interactions between the macrocy-
cles.
Conformation C, the next highest in energy, shows a cofa-
cial arrangement of the chlorin subunits and is structurally
similar to the arrangement of the special-pair chlorins of the
bacterial photosynthetic reaction centre. In contrast to the
natural special pair (Figure 1) with an average distance of
3.4 Š between the two subunits, the artificial pair exhibits a
distance of 7.5 Š between the centres of the monomers.
Conformation A is the highest in energy and the two
chlorin subunits have again a perpendicular orientation;
however, in contrast to conformation B, which has a roof-
like shape, one side of the roof here is turned outside
around one edge. It is most likely that additional energeti-
cally favoured conformations exist, but it is impossible to
1
lecular formula of C67H66N10O3Zn2. H NMR and 13C NMR
1
spectra each consisted of two sets of H and 13C spectroscop-
ic signals, respectively, which represented the two subunits.
1
13
À
À
The H and C signals of the CO NH CH2 part occurred
at d=6.69 (NH) and 2.93/3.29 ppm (CH2) for the protons
and at d=170.0 (CO) and 45.3 ppm (CH2) for the 13C atoms.
The molar extinction coefficients of the UV/visible spec-
tra of 24 showed double intensities (24: lmax (e)=618
(87900), 395 nm (218000 molÀ1 dm3 cmÀ1)) compared to the
monomers (for example, 19: lmax (e)=620 (33600), 396 nm
(84900 molÀ1 dm3 cmÀ1)). The unchanged positions of the ab-
sorption bands of dyad 24 compared with those of the mon-
omeric structure 21 also indicate that the two chlorin subu-
nits do not interact electronically. The CD spectrum of dyad
24 is more complicated than those of the monomeric chlor-
ins 19 and 21.
The energetically preferred perpendicular conformation B
of the chlorin subunits of dyad 24 follows from semi-empiri-
cal PM3 calculations (Figure 2). From a cofacial arrange-
ment, as found in the special pair of the bacterial photosyn-
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F.-P. Montforts et al.
6-CH), 3.74 (m, 3J=4.03 Hz, 1H; 4-CH), 5.23 (AB, 2J=12.67 Hz, 2H;
CO2CH2Ph), 6.66 (d, 3J=2.88 Hz, 1H; 3-CH), 6.95 (brs, 2H; NH), 7.34
(m, 1H; Hp), 7.41 (m, 2H; Ho), 7.48 (m, 2H; Hm), 7.57 (brs, 1H; NH),
11.11 ppm (brs, 1H; 2-NH); IR (KBr): n˜ =3410 (NH), 3380 (NH), 1730
(C=O), 1700 (C=O), 1675 cmÀ1 (C=O); MS (EI, 70 eV, T=1688C): m/z
(%): 368 (21) [M+], 337 (3) [M+ÀOCH3], 277 (1) [M+ÀCH2Ph], 239
(48), 148 (19), 130 (100); elemental analysis: calcd (%) for C20H20N2O5:
C 65.21, H 5.47, N 7.60; found: C 65.35, H 5.60, N 5.72.
calculate the whole conformational space of the molecule
due to the extended size of dyad 24.
Conclusion
The conformational arrangement B found for the peptide-
linked chlorin–chlorin dyad mimics, more or less, the acces-
sory bacteriochlorophyll–bacteriopheophytin part of the
bacterial photosynthetic reaction centre (Figure 1). Howev-
er, similar spacial arrangements can also be found in photo-
synthetic systems I and II of plants. With the concept de-
scribed here, a module system is available which could be
applied for mimicking more complicated parts of the natu-
rally occurring photosynthetic systems.
1-Benzyl-6-methyl-[(4R,5S,6S,7S)-5-cyano-3-formyl-4,5,6,7-tetrahydro-
4,7-methano-2H-isoindole-1,6-dicarboxylate] (10): For preparation of the
Vilsmeier reagent, POCl3 (372 mL, 4.07 mmol, 10 equiv) was added to dry
DMF (1.2 mL) at 08C under an argon atmosphere and the mixture was
stirred for 15 min. The Vilsmeier reagent was added to a solution of 9
(150 mg, 0.407 mmol) in dry DMF (4 mL) cooled to 58C and the solution
was then heated for 2 h at 808C. The reaction was quenched by addition
of saturated sodium acetate solution (5 mL) and stirred for a further
20 min at 808C. Thereafter, the reaction mixture was diluted with water
(10 mL), extracted four times with CH2Cl2 and dried by filtration over
cotton wool. After removal of CH2Cl2, the DMF was evaporated by Ku-
gelrçhr distillation under reduced pressure. The brown residue was chro-
matographed on silica gel (20 g) with CH2Cl2/EtOAc 15:1 as the eluent
to give 10 as a colourless solid. For analytical purposes, the product was
crystallised from CHCl3/n-hexane. Yield: 92.4 mg (0.24 mmol, 60%); Rf =
0.23 (silica gel, CH2Cl2/EtOAc 15:1), 0.76 (silica gel, CH2Cl2/MeOH
10:1); m.p. 225–2278C; [a]2D0 =À49.0 (c=0.78 in CH2Cl2); 1H NMR
(200 MHz, CDCl3): d=2.25 (2dd, 2J=9.8, 3J=4J=1.5 Hz, 1H; 8-CH2),
2.36 (d, 2J=9.8 Hz, 1H; 8-CH2), 3.03 (dd, 3J=4.4, 4J=1.5 Hz, 1H;
CHCN), 3.39 (s, 3H; OCH3), 3.57 (dd (“t”), 3J=4.4 Hz, 1H; 6-CH), 4.01
(s, 1H; 4-CH), 4.09 (d, 3J=3.9 Hz, 1H; 7-CH), 5.33 (s, 2H; CO2CH2Ph),
7.43 (m, 5H; Ph), 9.54 (brs, 1H; NH), 9.69 ppm (s, 1H; CHO); 13C NMR
(50 MHz, CDCl3): d=33.83 (5-C), 44.34 (7-C), 44.72 (4-C), 52.22 (6-C),
52.73 (8-C), 52.85 (OCH3), 67.55 (CH2Ph), 120.78 (1-C), 121.53 (CN),
125.94 (3-C), 128.89, 129.14, 129.29 (2’-C, 3’-C, 4’-C), 135.47, 135.61 (1’-C,
7a-C), 139.62 (3a-C), 160.14 (CO2Bn), 171.35 (CO2CH3), 179.29 ppm
(CHO); IR (KBr): n˜ =3290 (NH), 2237 (CN), 1726 (C=O), 1668 cmÀ1
(C=O); MS (EI, 70 eV, T=1888C): m/z (%): 379 (5), 378 (14) [M+], 347
(2) [M+ÀOCH3], 319 (1) [M+ÀCO2CH3], 287 (2) [M+ÀCH2Ph], 267
(34) [M+ÀC5H5NO2], 239 (5) [M+ÀOCH3ÀOCH2Ph], 92 (9), 91 (100)
[CH2Ph+]; HRMS (EI): calcd for C21H18N2O5: 378.12157 [M+]; found:
378.12152.
Experimental Section
General: Starting materials were either prepared according to literature
procedures or were purchased from Fluka, Merck or Aldrich and used
without further purification. All solvents were purified and dried by stan-
dard methods. All reactions were carried out under argon. 1H NMR spec-
tra were measured with Bruker DPX-200 Avance or Avance NB-
360 MHz spectrometers; all chemical shifts were referenced to the tetra-
methylsilane lock signal. MS and HRMS were performed on a Finnigan
MAT 8200 spectrometer (EI (70 eV), DCI (NH3, 8 mAsÀ1) and ESI (sol-
vent)) while ESI-HRMS was performed with an APEX Qe9.4T instru-
ment (9.4 T superconducting magnet) with an Apollo II electrospray ion-
iser. IR spectra were measured with a Perkin–Elmer Paragon 500 FTIR
spectrometer. UV/visible analysis was carried out on a Varian Cary 50
spectrophotometer. Column chromatographic separations were per-
formed on silica gel (32–63 mm, 60 Š, ICN). Melting points are uncorrect-
ed and were determined on a Reichert Thermovar hot-stage apparatus or
on a Gallenkamp apparatus. Optical rotations were measured with a
Perkin–Elmer 243 polarimeter with a water-jacket cell length of 1 dm
and the concentration, c, is given in g100 mLÀ1. CD spectra were record-
ed on a JASCO J-600 spectropolarimeter with a water-jacket cell length
of 1 dm. Elemental analyses were performed by Mikroanalytisches Labo-
ratorium Beller, Gçttingen (Germany).
(4R,5S,6S,7S)-5-Cyano-3-formyl-6-(methoxycarbonyl)-4,5,6,7-tetrahydro-
4,7-methano-2H-isoindole-1-carboxylic acid (11): NEt3 (4 drops) was
added to a solution of 10 (348 mg, 0.92 mmol) in dry THF (3 mL). The
mixture was degassed three times under reduced pressure and placed
under an argon atmosphere. After addition of some milligrams of palladi-
um catalyst (10% palladium on activated charcoal), the system was evac-
uated three times and placed under hydrogen from a balloon fitted to the
reaction flask. The reaction mixture was stirred at room temperature
until complete conversion of the starting material, as monitored by TLC.
The catalyst was removed by filtration over Celite 521 and the filtrate
was concentrated in vacuo to afford 11 as colourless oil. Yield: 265 mg
(0.92 mmol, 99%); Rf =0.20 (silica gel, CH2Cl2/MeOH 9:1); [a]2D0 =À18.8
(c=1.63 in MeOAc); 1H NMR (200 MHz, [D6]DMSO): d=2.10 (AB,
2J=9.60, 4J=2.06 Hz, 2H; 8-CH2), 2.74 (dd, 3J=4.80, 4J=2.06 Hz; 5-
CH), 3.46 (s, 3H; OCH3), 3.69 (dd (“t”), 3J=4.46 Hz, 1H; 6-CH), 3.89
(d, 3J=4.11 Hz, 1H; 4-CH), 3.93 (s, 1H; 7-CH), 9.67 (s, 1H; 3-CHO),
12.20 (brs, H; 2-NH), 13.02 ppm (brs, 1H; 1-CO2H); IR (KBr): n˜ =3280
(NH, OH), 2240 (CN), 1730 (C=O), 1660 cmÀ1 (C=O); MS (EI, 70 eV,
T=1888C): m/z (%): 288 (10) [M+], 257 (3) [M+ÀOCH3], 229 (3) [M+
ÀCO2CH3], 211 (3), 177 (100) [M+ÀC5H5NO2], 159 (25), 149 (18), 131
(30); HRMS (EI): calcd for C14H12N2O5: 288.07462 [M+]; found:
288.07333; elemental analysis (rac-11): calcd (%) for C14H12N2O5: C
58.33, H 4.20, N 9.72; found: C 58.50, H 4.70, N 8.96.
1-Benzyl-6-methyl-[(4R,5S,6S,7S)-5-carbamoyl-4,5,6,7-tetrahydro-4,7-
methano-2H-isoindole-1,6-dicarboxylate] (9): Benzyl isocyanide (266 mg,
1.5 mmol, 2.5 equiv) was dissolved in dry THF (1 mL) and then a solu-
tion of potassium tert-butylalcoholate (170 mg, 1.5 mmol, 2.5 equiv) in
dry THF (5 mL) was added quickly under an argon atmosphere and the
mixture was vigorously stirred at room temperature. After 5 min, a solu-
tion of (À)-(1R,2R,3R,6S,7S,9R)-5-oxo-2-exo-(phenylsulfonyl)-4-oxatricy-
clo[4.2.1.03.7]nonane-9-exo-carboxamide (8,[9a] 195 mg, 0.6 mmol) in dry
THF (15–20 mL) was added to the colourless suspension. After 1 h of
stirring at room temperature, the reaction mixture was quenched by addi-
tion of brine and stirred for a further 20 min. The organic layer was sepa-
rated and washed with sodium bicarbonate solution. The combined aque-
ous layers were acidified to pH 2 with a 2n solution of HCl and were ex-
tracted four times with ethyl acetate. The organic layers were dried by fil-
tration over cotton wool and concentrated in vacuo. The colourless resi-
due was dissolved in dry THF and treated with diazomethane until no
more N2 evolved. Thereafter, the solvent was removed in vacuo and the
yellow crude product was chromatographed on silica gel with elution
with CH2Cl2/MeOH 9:1. After removal of the eluent in vacuo, 9 was ob-
tained as a yellow oil. For analytical purposes, the product was crystal-
lised from CHCl3/n-hexane. Yield: 160 mg (0.434 mmol, 73%); Rf =0.38
(silica gel, CH2Cl2/MeOH 9:1); [a]2D0 =À85.8 (c=3.74 in CH2Cl2); m.p.
1808C (racemic); 1H NMR (360 MHz, [D6]DMSO): d=1.72 (d, 2J=
8.64 Hz, 1H; 8-CH2), 2.08 (d, 2J=8.64 Hz, 1H; 8-CH2), 2.50 (m, 1H; 5-
CH), 3.25 (s, 3H; OCH3), 3.32 (m, 1H; 7-CH), 3.53 (t, 3J=4.32 Hz, 1H;
5-Methyl-[(4S,5S,6S,7R)-3-bromo-6-cyano-1-formyl-4,5,6,7-tetrahydro-
4,7-methano-2H-isoindole-5-carboxylate] (12): A solution of 11 (33.1 mg,
115 mmol) in dry CH2Cl2 (5 mL) was added to a solution of pyridinium
perbromide (61 mg, 172.4 mmol, 1.5 equiv) in dry CH2Cl2 (5 mL) and dry
pyridine (46 mL, 575 mmol, 5 equiv). The mixture was stirred overnight at
6600
www.chemeurj.org
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 6595 – 6604

Photosynthesis Model Compound
FULL PAPER
room temperature. The reaction mixture was then washed with a 1n solu-
tion of HCl. The organic phases were washed with a saturated solution of
sodium bicarbonate, dried by filtration over cotton wool and concentrat-
ed in vacuo. The brown residue was chromatographed on silica gel with
CH2Cl2/MeOH 9:1 as the eluent to afford 12 as a brownish solid. The
product was crystallised from CH2Cl2/n-hexane for analytical characteri-
sation. Yield: 16.7 mg (51.6 mmol, 45%); Rf =0.60 (silica gel, CH2Cl2/
MeOH 9:1); m.p. 1208C; [a]2D0 =À4.9 (c=0.58 in CH2Cl2); 1H NMR
(7-CH, 4-CH), 52.31, 52.76 (8-C, 6-C, OCH3), 96.44 (3-C), 113.33 (3a-C),
121.31 (3-CN), 121.53 (5-CN), 134.23 (7a-C), 139.67 (1-C), 161.62
(CO2H), 171.22 ppm (CO2CH3); IR (KBr): n˜ =3467 (OH), 3292 (NH),
2224 (CN), 1716 cmÀ1 (C=O); MS (EI, 70 eV, T=2508C): m/z (%): 286
(3), 285 (15) [M+], 254 (5) [M+ÀOCH3], 227 (2), 226 (4) [M+
ÀCO2CH3], 225 (2) [M+ÀCO2CH3ÀH], 208 (4), 207 (3), 181 (4) [M+
ÀCO2CH3ÀCO2H], 180 (4) [M+ÀCO2CH3ÀCO2HÀH], 175 (11), 174
(100) [M+ÀC5H5NO2], 157 (6), 156 (53), 155 (5), 130 (9), 129 (11) [M+
ÀC5H5NO2ÀCO2H], 112 (18) [C5H5NO2++H], 102 (5), 101 (4), 80 (6)
2
4
(200 MHz, CDCl3): d=2.23 (dq, J=10.08, J=1.77 Hz, 1H; 8-CH2), 2.32
(dm, 2J=10.08 Hz, 1H; 8-CH2), 3.03 (dd, 3J=4.25, 4J=1.77 Hz, 1H; 6-
+
[C5H5NO2 ÀOCH3]; HRMS (EI): calcd for C14H11N3O4: 285.07496 [M+];
3
3
CH), 3.51 (t, J=4.25 Hz, 1H; 5-CH), 3.69 (s, 3H; OCH3), 3.78 (dm, J=
4.25 Hz, 1H; 7-CH), 3.99 (m, 1H; 4-CH), 9.15 (brs, 1H; NH), 9.42 ppm
(s, 1H; 1-CHO); IR (KBr): n˜ =3330 (NH), 2235 (CN), 1715 (C=O),
1655 cmÀ1 (C=O); MS (EI, 70 eV, T=1408C): m/z (%): 324 (42) [M+
found: 285.07468.
5-Methyl-[(4S,5S,6S,7R)-1,6-dicyano-3-(hydroxymethyl)-4,5,6,7-tetrahy-
dro-4,7-methano-2H-isoindole-5-carboxylate] (15): SOCl2 (0.47 mL,
6.46 mmol, 20 equiv) was injected with a syringe through a septum into a
solution of 14 (92.3 mg, 0.323 mmol) in dry THF (5 mL) under an argon
atmosphere. The reaction mixture was heated at 508C for 2 h. Thereafter,
the solvent and SOCl2 were removed in vacuo with an oil pump. The
acid chloride intermediate was dissolved in dry THF (10 mL) and cooled
to À808C under an argon atmosphere. Afterwards, a 1m solution of lithi-
A
G
ÀCO2CH3], 243 (5) [M+ÀBr], 213 (100) [M (81Br)ÀC5H5NO2], 211 (94)
+A
[M
calcd for C13H11BrN2O3: 321.99530 [M+]; found: 321.99520.
1-Benzyl-6-methyl-[(4R,5S,6S,7S)-3,5-dicyano-6-(4,5,6,7-tetrahydro-4,7-
methano-2H-isoindole-1,6-dicarboxylate] (13): Sodium acetate (300 mg,
3.648 mmol, 6 equiv) and hydroxylamine hydrochloride (212 mg,
um-9-borabicycloCAHTRE[UNG 3.3.1]nonane hydride in THF (0.65 mL, 0.646 mmol,
2 equiv) was injected dropwise with a syringe through a septum. The re-
action mixture was warmed to room temperature within 30 min and
stirred for a further 15 min. The reaction was quenched by addition of
NaCl solution (15 mL) and transferred into a separating funnel after
being stirred for 15 min. The aqueous layer was extracted three times
with CH2Cl2. The combined organic layers were dried by filtration over
cotton wool and concentrated in vacuo. The crude product was purified
by two-fold column chromatography on silica gel (with CH2Cl2/EtOAc
15:1 followed by CH2Cl2/MeOH 20:1 as the eluents) and then crystallised
from CHCl3/n-hexane to give 15 as colourless crystals. Yield: 53 mg
(19.6 mmol, 60%); Rf =0.24 (silica gel, CH2Cl2/MeOH 20:1); 1H NMR
(200 MHz, CDCl3 +10% DMSO): d=2.01 (dd, 2J=10.1, 3J=4J=1.7 Hz,
1H; 8-CH2), 2.13 (d, 2J=10.1 Hz, 1H; 8-CH2), 2.76 (dd, 3J=3.9, 4J=
2.0 Hz, 1H; 6-CH), 3.37 (dd (“t”), 3J=3.9 Hz, 1H; 5-CH), 3.52 (s, 3H;
OCH3), 3.69 (s, 2H; 4-CH, 7-CH), 4.34 (d, 2H; 3-CH2), 10.67 ppm (brs,
1H; OH); 13C NMR (50 MHz, CDCl3 +10% DMSO): d=34.28 (6-C),
42.46 (7-CH), 44.82 (4-C), 51.71 (8-C), 53.00, 53.12 (5-C, OCH3), 56.55
(3-CH2), 91.96 (3-C), 114.46 (3a-C), 121.71 (6-CCN), 126.92 (1-CCN),
130.76 (1-C), 139.74 (7a-C), 171.68 ppm (CO2CH3); IR (KBr): n˜ =3360
(NH, OH), 2219 (CN), 1724 cmÀ1 (C=O); MS (EI, 70 eV, T=1768C): m/z
(%): 272 (6), 271 (43) [M+], 254 (3) [M+ÀOH], 253 (3), 240 (9) [M+
ÀOCH3] + [M+ÀCH2OH], 222 (5) [M+ÀOCH3ÀCH2OH], 213 (4), 212
(3) [M+ÀCO2CH3], 211 (3) [M+ÀCO2CH3ÀH], 194 (10) [M+
ÀCO2CH3ÀOHÀH], 167 (4), 160 (100) [M+ÀC5H5NO2], 159 (14), 143
(21), 142 (60) [M+ÀC5H5NO2ÀOH], 131 (7), 130 (46) [M+
ÀC5H5NO2ÀCH2OH], 129 (13), 116 (4), 115 (6), 114 (4), 112 (2)
3.04 mmol, 5 equiv) were added to
a suspension of 10 (230 mg,
0.608 mmol) in methanol (10 mL). The mixture was stirred for 30 min at
room temperature. Thereafter, a saturated solution of NaCl (10 mL) was
added and the mixture was extracted three times with CH2Cl2. The com-
bined organic layers were washed twice with water, filtered over dry
cotton wool and concentrated in vacuo to afford the oxime of 10 as a col-
ourless solid with a yield of 229 mg (0.58 mmol, 96%). The oxime was
dissolved in dry CH2Cl2 and cooled to 28C under an argon atmosphere.
After addition of 1,1’-carbonyldiimidazole (152 mg, 0.936 mmol, 2 equiv),
the reaction mixture was stirred for 16 h at room temperature. The sol-
vent was removed in vacuo and the yellowish residue was chromato-
graphed on silica gel (30 g) with CH2Cl2/EtOAc 15:1 as the eluent to
afford 13 as a colourless solid. The product was recrystallised from
CHCl3/n-hexane for analytical purposes. Yield: 153.3 mg (40.8 mmol,
87%); Rf =0.37 (silica gel, CH2Cl2/EtOAc 15:1); m.p. 251–2538C; [a]D20
=
À53.4 (c=0.32 in CH2Cl2); 1H NMR (200 MHz, CDCl3): d=2.22 (dd,
2J=9.9, 3J=4J=1.6 Hz, 1H; 8-CH2), 2.34 (d, 2J=9.9 Hz, 1H; 8-CH2),
3.10 (dd, 3J=4.3, 4J=1.6 Hz, 1H; 5-CH), 3.45 (s, 3H; OCH3), 3.58 (dd
(“t”), 3J=4.3 Hz, 1H; 6-CH), 3.90 (s, 1H; 4-CH), 4.06 (d, 3J=4.0 Hz,
1H; 7-CH), 5.33 (s, 2H; CH2Ph), 7.45 (m, 5H; Ph), 9.54 ppm (brs, 1H;
NH); 13C NMR (50 MHz, CDCl3): d=33.61 (5-C), 44.87 (7-CH, 4-CH),
52.13 (6-C), 52.79 (8-C), 53.24 (OCH3), 67.67 (CH2Ph), 97.66 (3-C),
112.50 (3-CN), 119.69 (1-C), 121.25 (5-CN), 128.78, 129.20, 129.24 (2’-C,
3’-C, 4’-C), 134.42 (7a-C), 135.44 (1’-C), 140.04 (3a-C), 159.66 (CO2Bn),
172.11 ppm (CO2CH3); IR (KBr): n˜ =3272 (NH), 2228 (CN), 1718 cmÀ1
(C=O); MS (EI, 70 eV, T=1898C): m/z (%): 376 (4), 375 (17) [M+], 344
(3) [M+ÀOCH3], 265 (5), 264 (24) [M+ÀC5H5NO2], 246 (3), 202 (8), 107
(6), 92 (8), 91 (100) [CH2Ph+]; HRMS (EI): calcd for C21H17N3O4:
375.12191 [M+]; found: 375.12137.
+
[C5H5NO2++H], 90 (7), 83 (8), 80 (5) [C5H5NO2 ÀOCH3]; HRMS (EI):
calcd for C14H13N3O3 271.09569 [M+]; found: 271.09639.
5-Methyl-[(4R,5S,6S,7S)-1,6-dicyano-3-formyl-4,5,6,7-tetrahydro-4,7-
methano-2H-isoindole-5-carboxylate] (16): Cerium ammonium nitrate
(318 mg, 0.580 mmol, 5 equiv) was added to a stirred solution of 15
(31.5 mg, 0.116 mmol) in THF (1 mL), H2O (1 mL) and acetic acid
(1.2 mL) at room temperature. After 2 h, the reaction mixture was dilut-
ed with CH2Cl2 (10 mL) and washed with a saturated NaCl solution
(5 mL). The aqueous layer was extracted three times with CH2Cl2, the
combined organic extracts were dried by filtration over cotton wool and
the solvent was removed under reduced pressure. Crystallisation from
CHCl3/n-hexane afforded 16 as colourless crystals. Yield: 24 mg
(0.08 mmol, 77%); Rf =0.64 (silica gel, CH2Cl2/MeOH (20:1)); m.p. 205–
2078C; 1H NMR (200 MHz, CDCl3): d=2.30 (dd, 2J=10.1, 3J=4J=
1.7 Hz, 1H; 8-CH2), 2.43 (d, 2J=10.1 Hz, 1H; 8-CH2), 3.10 (dd, 3J=3.9,
4J=2.0 Hz, 1H; 6-CH), 3.66 (dd (“t”), 3J=3.9 Hz, 1H; 5-CH), 3.71 (s,
3H; OCH3), 3.96 (s, 1H; 7-CH), 4.14 (d, 3J=3.9 Hz, 1H; 4-CH), 9.55 (s,
1H; CHO), 9.94 ppm (brs, 1H; NH); 13C NMR (50 MHz, CDCl3): d=
33.77 (6-C), 43.41 (4-C), 44.46 (7-C), 52.34 (8-C), 52.50 (5-CH3), 53.63
(OCH3), 99.84 (1-C), 112.20 (1-CN), 120.95 (6-CN), 127.67 (3-C), 138.36
(3a-C), 140.37 (7a-C), 171.47 (CO2CH3), 178.61 ppm (CHO); IR (KBr):
n˜ =3325 (NH), 2231 (CN), 1714 (C=O), 1681 cmÀ1 (C=O); UV/Vis
(MeOH): lmax (e)=220 (10909), 284 nm (13841 molÀ1 dm3 cmÀ1); CD
(4R,5S,6S,7S)-3,5-dicyano-6-(methoxycarbonyl)-4,5,6,7-tetrahydro-4,7-
methano-2H-isoindole-1-carboxylic acid (14): Some drops of acetic acid
were added to a solution of 13 (137 mg, 0.365 mmol) in dry THF (6 mL).
The mixture was degassed three times under reduced pressure and
placed under an argon atmosphere. After addition of some milligrams of
palladium catalyst (10% palladium on activated charcoal), the system
was evacuated three times and placed under hydrogen from a balloon
fitted to the reaction flask. The reaction mixture was stirred at room tem-
perature until complete conversion of the starting material, as monitored
by TLC. The catalyst was removed by filtration over Celite 521 and the
filtrate was concentrated in vacuo to afford 14 as a colourless solid. For
analytical purposes 14 was crystallised from THF/n-hexane. Yield:
104 mg (36.4 mmol, 98%); Rf =0.1 (silica gel, CH2Cl2/EtOAc 15:1); m.p.
230–2328C; [a]2D0 =À14.7 (c=0.156 in CH2Cl2); 1H NMR (200 MHz,
2
3
CDCl3 +10% DMSO): d=2.12 (dd, J=9.9, J=4J=1.3 Hz, 1H; 8-CH2),
2.22 (d, 2J=9.9 Hz, 1H; 8-CH2), 2.88 (dd, 3J=4.3, 4J=1.3 Hz, 1H; 5-
CH), 3.46 (dd (“t”), 3J=4.3 Hz, 1H; 6-CH), 3.53 (s, 3H; OCH3), 3.77 (s,
3
1H; 4-CH), 4.02 (d, J=3.8 Hz, 1H; 7-CH), 11.46 ppm (brs, 1H; CO2H);
13C NMR (50 MHz, CDCl3 +10% DMSO): d=33.59 (5-C), 44.52, 44.84
Chem. Eur. J. 2007, 13, 6595 – 6604
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
6601

F.-P. Montforts et al.
3
(MeOH, c=4.7ꢂ10À5 molLÀ1): lmax ([V]m)=222 (10481), 265 nm
(À10832 degcm2 dmolÀ1); MS (EI, 70 eV, T=1508C): m/z (%): 270 (3),
269 (18) [M+], 238 (5) [M+ÀOCH3], 210 (5) [M+ÀCO2CH3], 209 (4)
[M+ÀCO2CH3ÀH], 181 (3) [M+ÀCO2CH3ÀCHO], 180 (2) [M+
ÀCO2CH3ÀCHOÀH], 159 (11), 158 (100) [M+ÀC5H5NO2], 130 (26), 129
(11) [M+ÀC5H5NO2ÀCHO], 112 (5) [C5H5NO2++H], 103 (4), 102 (5), 80
18-CH3, 14-CH3), 3.37 (s, 3H; 19-CH3), 3.98 (dd (“t”), J=2ꢂ3.9 Hz, 1H;
2-CH), 4.41 (AB, 2J=16.37 Hz, 2H; 9-CH2), 4.99 (2 s, 2H; 1-CH, 4-CH),
8.30 (s, 1H; 6-CH), 8.53 (s, 1H; 11-CH), 9.43 (s, 1H; 16-CH), 9.50 ppm
(s, 1H; 21-CH); UV/Vis (CHCl3): lmax (e)=620 (33622), 573 (4234), 496
(4008), 396 nm (84925 molÀ1 m3 cmÀ1); CD (CHCl3, c=1.2ꢂ10À5 molLÀ1):
lmax ([V]m)=618 (5019), 607 (À6751), 578 (16882), 553 (À5525), 541
(22558), 525 (À4968), 507 (À6581), 487 (À11917), 463 (À8013), 434
(À2089), 397 nm (20639 degcm2 dmolÀ1); MS (EI, 70 eV, T=3448C): m/z
(%): 607 (23) [M+], 496 (47) [M+ÀC5H5NO2] (retro-Diels–Alder reac-
tion), 466 (17), 451 (8); HRMS (EI): calcd for C34H33N5O2Zn: 607.19257
[M+]; found: 607.19320.
+
(4) [C5H5NO2 ÀOCH3]; HRMS (EI): calcd for C14H11N3O3: 269.08004
[M+]; found: 269.08063; elemental analysis: calcd (%) for C14H11N3O3 +
CHCl3 (0.06 equiv): C 61.09, H 4.03, N 15.2; found: C 60.96, H 3.88, N
15.18 (the content of solvent in the crystalline sample was confirmed by
1H NMR spectroscopy).
Preparation of chlorin subunit 19:
Preparation of chlorin subunit 21:
A
ACHTRE[UGN Methyl-(1S,2S,3S,4R,21RS)-3,5,21-tricyano-1,2,3,4,19,20,21,25-octahydro-
tahydro-9,10,14,15,20,20,21-heptamethyl-1,4-methano-23H-benzo[b]bilin-
2-carboxylato]zinc(II) (18): A 5n solution of potassium hydroxide in
MeOH/H2O (9:1, 4 mL) was added to a solution of [ethyl-(14RS)-(14-
cyano-12,13,14,17-tetrahydro-2,3,7,8,13,13,14-heptamethyl-15H-tripyrrin-
1-carboxylato)]nickel(II) (rac-17; 31.2 mg, 65.44 mmol) in dry THF
(6 mL). The mixture was heated at 708C for 45 min under an argon at-
mosphere. After being cooled, the reaction mixture was diluted with
CH2Cl2 (20 mL) and washed with NaHCO3 solution (20 mL). The aque-
ous layer was vigorously extracted with CH2Cl2 and the combined organ-
ic layers were dried by filtration over cotton wool and concentrated in
vacuo to afford the free carboxylic acid derivative of rac-17. Degassed
solutions of 12 (31.7 mg, 98.17 mmol, 1.5 equiv) in dry CHCl3 (4 mL) and
0.4n para-toluenesulfonic acid in CHCl3 (1.64 mL, 654.4 mmol, 10 equiv)
were successively added with a syringe through a septum to the degassed
carboxylic acid under an argon atmosphere. The mixture was stirred
under reflux for 20 min. The blue-green reaction mixture was diluted
with CH2Cl2, poured into a separating funnel containing a NaHCO3 solu-
tion (20 mL) and vigorously extracted with CH2Cl2. The combined organ-
ic layers were dried by filtration over cotton wool and concentrated in
vacuo. The metal-free bilin system of 18 was used for complexation with-
out further purification. A solution of dry zinc(II) acetate (60.0 mg,
327 mmol, 5 equiv) and sodium acetate (27 mg, 327 mmol, 5 equiv) in dry
methanol (3 mL) was added to a solution of metal-free bilin 18 in dry
CH2Cl2 (6 mL). The mixture was allowed to react at room temperature
for 20 min under an argon atmosphere. The reaction mixture was trans-
ferred into a separating funnel containing a solution of NaHCO3 (10 mL)
and vigorously extracted with CH2Cl2. The organic layers were dried by
filtration through cotton wool and concentrated under reduced pressure.
The residue was chromatographed on silica gel with CH2Cl2/EtOAc/NEt3
9:1:0.05 as the eluent to yield 18 as a green solid consisting of a mixture
of diastereomers. Yield: 24.4 mg (0.034 mmol, 52%); Rf =0.71 and 0.67
(silica gel, CH2Cl2/EtOAc 9:1); UV/Vis (CHCl3): lmax (e)=733 (0.73),
671 (0.47), 504 (0.27), 383 (1), 328 (0.5), 282 nm (0.83 molÀ1 dm3 cmÀ1);
MS (DCI negative): m/z (%): 714 (13) [MÀ], 687 (8) [MÀÀHCN]. Com-
pound 18 was used for the next synthetic step without further characteri-
sation because of its instability.
9,10,14,15,20,20,21-heptamethyl-1,4-methano-23H-benzo[b]bilin-2-car-
boxylato]zinc(II) (20): A 5n solution of potassium hydroxide in MeOH/
H2O (9:1, 1.9 mL) was added to a solution of rac-17 (11.7 mg, 24.5 mmol)
in dry THF (2.5 mL). The mixture was heated at 708C for 30 min under
an argon atmosphere. After cooling, the reaction mixture was diluted
with CH2Cl2 and washed with NaHCO3 solution (15 mL). The aqueous
layer was vigorously extracted with CH2Cl2 and the combined organic
layers were dried by filtration over cotton wool and evaporated in vacuo
to afford the free carboxylic acid derivative of 17. Degassed solutions of
16 (12.2 mg, 45.3 mmol) in dry CHCl3 (2 mL) and 0.4n para-toluenesul-
fonic acid in CHCl3 (0.55 mL, 220 mmol, 9 equiv) were successively added
with a syringe through a septum to the degassed carboxylic acid under an
argon atmosphere. The mixture was stirred under reflux for 30 min. The
blue-green reaction mixture was diluted with CH2Cl2, transferred into a
separating funnel containing NaHCO3 solution (15 mL) and vigorously
extracted by CH2Cl2. The combined organic layers were dried by filtra-
tion through cotton wool, evaporated in vacuo and purified by column
chromatography on silica gel with CH2Cl2/EtOAc 15:1 as the eluent. The
eluted blue fraction was dried in vacuo with an oil pump to give the
metal-free bilin 20 (8.9 mg, 61%), which was complexed without further
purification and characterisation.
A solution of dry zinc(II) acetate
(19.0 mg, 103.4 mmol, 6.8 equiv) and sodium acetate (8.5 mg, 103.4 mmol,
6.8 equiv) in dry methanol (1.5 mL) was added to the solution of the
metal-free bilin 20 in dry CH2Cl2. The mixture was allowed to react at
room temperature for 40 min under an argon atmosphere. The green-col-
oured reaction mixture was transferred into a separating funnel contain-
ing a solution of NaHCO3 (15 mL) and was vigorously extracted with
CH2Cl2. The organic layers were dried by filtration through cotton wool
and the solvent was removed in vacuo. The residue was chromatographed
on silica gel with CH2Cl2/EtOAc 15:1 as the eluent and crystallised from
CHCl3/n-hexane to give 20 as a green solid: Yield=6.2 mg (9.3 mmol,
61%); Rf =0.80 (silica gel, CH2Cl2/EtOAc 15:1); MS (ESI, MeOH, posi-
tive): 661 [M+], 684 [M+Na+]; MS (ESI, MeOH, negative): 660
AHCTREUNG
AHCTREUNG
A
amethyl-1,4-methano-23H,25H-benzo[b]porphin-2-carboxylato]}zinc(II)
(21): A carefully degassed solution of 20 (8.1 mg, 12.2 mmol) in dry 1,2,4-
trichlorobenzene (4 mL) was heated at 2108C for 40 min. After the reac-
tion mixture had cooled to room temperature, the solvent was removed
by Kugelrçhr distillation at 608C in vacuo. The green residue was chro-
matographed on silica gel with CH2Cl2/MeOH 99:1 as the eluent and
crystallised from CHCl3/n-hexane to give 21 as green crystals. Yield:
3.12 mg (5.12 mmol, 42%); Rf =0.66 (silica gel, CH2Cl2/MeOH 99:1), 0.90
(silica gel, CH2Cl2/EtOAc 9:1); m.p. >2508C (decomp); 1H NMR
(600 MHz, CDCl3): d=2.02, 2.09 (2s, 6H; 2ꢂ8-CH3), 2.90 (2ꢂdd, 2J=
9.2, 3J=2ꢂ1.4 Hz, 1H; 27-CH2), 2.98 (2ꢂddd, 2J=9.4, 3,4J=3ꢂ1.7 Hz,
1H; 27-CH2), 3.16 (dd, 3J=4.2, 4J=1.8 Hz, 1H; 3-CH), 3.18 (s, 3H; 19-
CH3), 3.20 (s, 3H; 13-CH3), 3.31 (2 s, 6H; 14-CH3, 18-CH3), 3.32 (s, 3H;
OCH3), 4.00 (dd (“t”), 3J=2ꢂ4.1 Hz, 1H; 2-CH), 4.54 (brs, 2H; 9-CH2),
4.94 (brs, 1H; 4-CH), 5.11 (d, 3J=4.2 Hz, 1H; 1-CH), 8.53 (s, 1H; 6-
CH), 8.60 (s, 1H; 11-CH), 9.35 (s, 1H; 16-CH), 9.39 ppm (s, 1H; 21-CH);
IR (KBr): n˜ =2229 (CN), 1741 cmÀ1 (C=O); UV/Vis (CHCl3): lmax (e)=
620 (25757), 580 (5185), 500 (5347), 400 (78461), 300 (19984), 280 nm
(18735 molÀ1 dm3 cmÀ1); CD (CHCl3, c=1.05ꢂ10À5 molLÀ1): lmax
amethyl-1,4-methano-23H,25H-benzo[b]porphin-2-carboxylato}]zinc(II)
(19): A degassed solution of 18 (24.4 mg, 34.03 mmol), DBU (1.02 mL,
6.806 mmol, 200 equiv) and some milligrams of ZnCAHTRE(UNG AcO)2 in dry sulfo-
lane (3 mL) was heated at 608C for 2 h under an argon atmosphere.
After being cooled to room temperature, the reaction mixture was dilut-
ed with benzene (20 mL), transferred into
washed three times with a saturated NaCl solution (15 mL). The com-
bined aqueous layers were re-extracted with benzene (5 mL). The organ-
ic extracts were dried by filtration over cotton wool and evaporated in
vacuo. The residual sulfolane was removed by Kugelrçhr distillation at
808C in vacuo with an oil pump. The dark-green residue was purified by
column chromatography on silica gel with CH2Cl2/EtOAc/NEt3 9:1:0.05
as the eluent to yield 19 as a turquoise-blue solid. For analytical charac-
terisation, the product was crystallised from CHCl3/n-hexane: Yield=
8.3 mg (13 mmol, 40%); Rf =0.69 (silica gel, CH2Cl2/EtOAc 9:1);
1H NMR (200 MHz, CDCl3 +20 mL [D5]pyridine): d=1.75 (s, 3H; 8-
CH3), 1.95 (s, 3H; 8-CH3), 2.85 (s, 1H; 27-CH2), 2.92 (m, 1H; 27-CH2),
3.08 (s, 3H; OCH3), 3.25 (s, 4H; 13-CH3, 3-CH), 3.323, 3.327 (2 s, 6H;
6602
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Chem. Eur. J. 2007, 13, 6595 – 6604

Photosynthesis Model Compound
FULL PAPER
([V]m)=620
(18514),
596
(8933),
570
(À9119),
397 nm
(360 MHz, CD2Cl2): d=1.91, 1.97 (2s, 6H; 2ꢂ22-CH3), 2.04, 2.05 (2s,
6H; 2ꢂ2-CH3), 2.2 (s, 1H; 63-CH), 2.29, 2.57 (m, 2H; 61-CH2), 2.86, 2.95
(m, 2H; 48-CH2), 2.93, 3.29 (m, 2H; 65-CH2), 3.19 (s, 3H; 27-CH3), 3.24
(s, 3H; 7-CH3), 3.27 (m, 1H; 50-CH), 3.29 (m, 1H; 64-CH), 3.32 (s, 3H;
28-CH3), 3.35 (s, 6H; 8-CH3, 32-CH3), 3.37 (s, 9H; 12-CH3, 13-CH3, 64-
CH3), 3.39 (s, 3H; 33-CH3), 3.87 (s, 1H; 51-CH), 4.02 (s, 1H; 62-CH),
4.48 (s, 2H; 23-CH2), 4.56 (s, 2H; 3-CH2), 4.87 (s, 2H; 47-CH, 60-CH),
4.91 (s, 1H; 49-CH), 6.69 (s, 1H; NH), 8.45 (s, 1H; 40-CH), 8.59 (s, 1H;
25-CH), 8.61 (s, 1H; 20-CH), 8.66 (s, 1H; 5-CH), 9.33 (s, 1H; 15-CH),
9.41 (s, 1H; 30-CH), 9.45 (s, 1H; 10-CH), 9.51 ppm (s, 1H; 35-CH);
13C NMR (90 MHz, CD2Cl2): d=11.6 (7-CH3, 27-CH3), 11.7 (8-CH3, 28-
CH3), 11.8 (12-CH3, 13-CH3), 31.2 (2ꢂ22-CH3), 31.3, 31.4 (2ꢂ2-CH3),
33.5 (50-CH), 44.7 (62-CH), 45.3 (65-CH2), 45.4 (22-C), 45.5 (2-C), 45.8
(60-CH), 47.0 (63-CH), 47.7 (49-CH), 47.8 (47-CH), 51.5 (23-CH2), 51.6
(3-CH2), 52.0 (32-CH3, 33-CH3, 64-CH3), 53.0 (61-CH2), 53.5 (64-CH),
54.5 (51-CH), 55.1 (48-CH2), 93.4 (20-CH, 40-CH), 93.5 (5-CH), 99.3 (25-
CH), 99.8 (10-CH), 99.9 (30-CH), 103.5 (15-CH), 104.1 (35-CH), 123.4
(52-CN), 133.2 (27-C), 133.7 (7-C), 134.1 (32-C), 134.4 (12-C), 135.0 (13-
C, 33-C), 137.0 (16-NC), 137.5 (36-NC), 138.1 (28-C), 138.4 (8-C), 143.1
(19-NC), 143.3 (39-NC), 144.66 (14-NC), 144.7 (34-NC), 146.0 (18-C),
146.4 (29-NC), 146.6 (31-NC), 147.1 (11-NC), 149.0 (9-NC), 149.8 (17-C),
149.8 (38-C), 151.6 (37-C), 152.9 (26-NC), 153.3 (6-NC), 159.8 (24-NC),
160.3 (4-NC), 169.4 (21-NC), 169.5 (1-NC), 170.0 (53-CO), 175.0 ppm
(64-COO); UV/Vis (CH2Cl2): lmax (e)=618 (87915), 574 (23119), 5023
(24501), 395 nm (217921 molÀ1 dm3 cmÀ1); CD (CH2Cl2, c=4.2ꢂ
10À6 molLÀ1): lmax ([V]m)=617 (64052), 587 (À46906), 569 (À37155),
554 (29471), 542 (À18515), 528 (45942), 489 (À10648), 473 (10363), 458
(À6648), 429 (À12030), 398 (À25610), 379 nm (À45076 degcm2 dmolÀ1);
MS (ESI, CH2Cl2/MeOH 1:100, positive): 1187 ([M+H+], 1209 [M+Na+
], 1225 [M+K+]; MS (ESI, CH2Cl2/MeOH 1:100, negative): 1185 [MÀH+
], 1221 [M+ClÀ]; HRMS (ESI, positive): calcd for C67H66N10O3Zn2:
1186.33968 [M+]; found: 1186.33968.
(À68405 degcm2 dmolÀ1); MS (EI, 70 eV, T=3448C): m/z (%): 607 (65)
[M+], 496 (100) [M+ÀC5H5NO2] (retro-Diels–Alder reaction), 466 (24)
[M+ÀC5H5NO2ÀCHOÀH], 451 (12), 248 (12), 91 (14), 49 (25); MS
(DCI, negative, NH3, 8 mAsÀ1): m/z (%): 708 (15), 607 (50) [M+], 468
(9), 398 (4), 307 (23), 293 (42), 141 (41), 111 (100) [C5H5NO2+]; HRMS
(EI): calcd for C34H33N5O2Zn: 607.19103 [M+]; found: 607.19257.
Preparation of dyad 24:
[(2’,5’-Dioxopyrrolidin-1’-yl)(1S,2S,3S,4R)-3-cyano-1,2,3,4,8,9-hexahydro-
8,8,13,14,18,19-hexamethyl-1,4-methano-23H,25H-benzo[b]porphin-2-car-
boxylato]zinc(II) (22): A 5n solution of potassium hydroxide in metha-
nol/water (9:1, 0.5 mL) was added to a solution of 21 (2.6 mg, 4.3 mmol)
in THF (1 mL). The reaction mixture was heated at 608C for 40 min
under an argon atmosphere. After being cooled to room temperature,
the mixture was diluted with CH2Cl2 and washed with sodium chloride
solution. The combined organic extracts were dried by filtration over
cotton wool. Evaporation of the solvent and drying in vacuo afforded the
crude free carboxylic acid derivative of 21 in an almost quantitative
yield. For the activation reaction, the carboxylic acid was dissolved in dry
CH2Cl2 (1 mL), then DCC (17.6 mg, 85.2 mmol, 20 equiv) and NHS
(9.8 mg, 85.2 mmol, 20 equiv) were added. The mixture was stirred for
90 min at room temperature under an argon atmosphere. After evapora-
tion of the solvent, the residue was purified by column chromatography
on silica gel with CH2Cl2/EtOAc 15:1 as the eluent and crystallised from
CHCl3/n-hexane to yield 22 as blue-green crystals. Yield: 1.86 mg
(2.7 mmol, 63%); Rf =0.64 (silica gel, CH2Cl2/EtOAc 9:1); m.p. >2008C
(decomp); 1H NMR (200 MHz, CDCl3): d=2.03, 2.07 (2s, 6H; 2ꢂ8-
CH3), 2.47 (brs, 4H; 3’-CH2, 4’-CH2), 3.00 (m, 2H; 27-CH2), 3.20 (m,
1H; 3-CH), 3.22 (s, 3H; 19-CH3), 3.33, 3.34 (2s, 6H; 14-CH3, 18-CH3),
3.42 (s, 3H; 13-CH3), 4.32 (dd, 3J=4.1 Hz, 1H; 2-CH), 4.54 (brs, 2H; 9-
CH2), 5.01 (brs, 1H; 4-CH), 5.30 (d, 3J=4.2 Hz, 1H; 1-CH), 8.52 (s, 1H;
6-CH), 8.61 (s, 1H; 11-CH), 9.40 (s, 1H; 16-CH), 9.66 ppm (s, 1H; 21-
CH); IR (KBr): n˜ =2238 (CN), 1742 (C=O), 1724 cmÀ1 (C=O); UV/Vis
(CHCl3): lmax (e)=620 (37802), 579 (4880), 502 (3816), 401 (103971),
294 nm (10892 molÀ1 dm3 cmÀ1); MS (ESI, CH2Cl2/MeOH 1:1000, posi-
tive): 690 [M+], 713 [M+Na+], 792 [M+K+]; MS (ESI, CH2Cl2/MeOH
1:1000, negative): 592 [MÀC4H4NO2], 689 [MÀH+], 725 [M+ClÀ]. Com-
pound 21 was used for the next reaction step without further characteri-
sation because of its sensitivity.
Acknowledgements
We thank Priv. Doz. H. Rosemeyer (Department of Chemistry, Universi-
ty of Osnabrück) for CD measurements and Dr. T. Dülcks, Dipl.-Ing. D.
Kemken, Dipl.-Ing. J. Stelten, Dipl.-Chem. J. Willmann and Professor D.
Leibfritz (Institute of Organic Chemistry, University of Bremen) for
NMR and mass spectrometry measurements.
ACHTREUNG
A
(3.8 mg, 16 mmol, 10 equiv) in water (0.3 mL) was added to a solution of
21 (1.1 mg, 1.6 mmol) in THF (0.6 mL). The deep-blue solution was
cooled to 08C and sodium borohydride (3.9 mg, 96 mmol, 60 equiv) was
added in small portions under a hydrogen atmosphere. After 20 min, the
cooling bath was removed and the reaction mixture was stirred for an ad-
ditional 2 h at room temperature. To increase the yield, the black cobalt
boride residue was treated with ultrasound every 20 min. The free amine
23 was obtained by addition of some drops of a concentrated ammonium
solution. After stirring for 15 min, the reaction mixture was diluted with
CH2Cl2 and washed with water. The aqueous layer was extracted three
times with CH2Cl2. The combined organic layers were dried by filtration
over cotton wool. After evaporation of the solvent, the residue was dried
in vacuo to give 23 as a green solid. Yield: 0.6–0.8 mg (1–1.3 mmol, 60–
80%); Rf =0.01 (silica gel, CH2Cl2/EtOAc 15:1), 0.42 (Alox, CH2Cl2/
MeOH/Et3N 20:1:0.5); MS (ESI MS/MS, CH2Cl2/MeOH 1:100, positive):
612 [M+H+], 595 [MÀNH2+], 583 [MÀCH2NH+], 580 [MÀCH3OH+],
496 [MÀC5H9NO2+]; MS (ESI, CH2Cl2/MeOH 1:50, negative): 646
[M+ClÀ]. Compound 23 was used for the next reaction step without fur-
ther characterisation because of its sensitivity.
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A solution of 22 (1.5 mg, 2.1 mmol), 23 (5.2 mg,
8.5 mmol, 4 equiv) and a catalytic amount of DMAP in dry THF (2 mL)
was stirred for 4 h under an argon atmosphere. The solvent was then
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www.chemeurj.org
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Received: February 7, 2007
Published online: May 22, 2007
6604
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ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2007, 13, 6595 – 6604