Efficient synthesis of B- and C-rings components of phycobilin derivatives for structure/function analysis of phytochrome

Article abstract of DOI:10.1246/cl.2000.492

B- and C-Rings components of phycobilin derivatives were efficiently prepared starting from the corresponding lactones. This synthetic method made it possible to prepare not only phycocyanobilin (PCB), but also PCB derivatives having butanoic acid side chain(s) instead of propanoic one(s), regioselectively monoesterified PCB derivatives at C8 or C12, and regioisomers of PCB with respect to methyl and propanoic acid substituents of B- and C-rings for the first time toward the structure/function analysis of phytochrome.

Full text of DOI:10.1246/cl.2000.492

492
Chemistry Letters 2000
Efficient Synthesis of B- and C-Rings Components of Phycobilin Derivatives
for Structure/Function Analysis of Phytochrome
Atsuko Ohta, Daisuke Sawamoto, Krishanthi Padmarani Jayasundera, Hideki Kinoshita, and Katsuhiko Inomata*
Department of Chemical Science, Graduate School of Natural Science and Technology, Kanazawa University,
Kakuma, Kanazawa, Ishikawa 920-1192
(Received February 9, 2000; CL-000139)
B- and C-Rings components of phycobilin derivatives were
Previously we reported the convenient method for the prepa-
ration of a common pyrrole precursor to B- and C-rings starting
from methyl 4-oxobutanoate (12c) readily available by
rhodium(I) catalyzed hydroformylation of methyl acrylate.2a
Compound 12c is also available from methyl 4-nitrobutanoate by
Nef reaction.4 On the other hand, we have found that allyl ester is
the most suitable protecting group for the carboxylic acid moiety
at C8 and C12 of phycobilin derivatives to synthesize their free
acid forms possible to assemble with the apoproteins.2b However,
since it was not easy to directly prepare allyl 4-oxopropanoate
(12a) by the above methods, we developed a new and extremely
convenient method which can provide not only the desired 12a
but also other derivatives such as 12b-d useful for production of
a variety of phycobilins depending upon the using alcohols
(ROH) and the starting lactones (10) as shown in Scheme 1.
efficiently prepared starting from the corresponding lactones.
This synthetic method made it possible to prepare not only phy-
cocyanobilin (PCB), but also PCB derivatives having butanoic
acid side chain(s) instead of propanoic one(s), regioselectively
monoesterified PCB derivatives at C8 or C12, and regioisomers
of PCB with respect to methyl and propanoic acid substituents of
B- and C-rings for the first time toward the structure/function
analysis of phytochrome.
Phycocyanin and phytochrome are chromoproteins widely
concerned with the photosynthetic light-harvesting systems of
cyanobacteria or red algae and the regulation of plant gene
expression by light, respectively. The chromophores named phy-
cocyanobilin (PCB, 1) and phytochromobilin (PΦB, ethyl group
at C18 of 1 is replaced to vinyl group) are linear tetrapyrrole
derivatives and covalently bound to their apoproteins at A-ring.1
For the structure/function analysis of phytochrome, we have been
studying on the synthesis of phycobilin derivatives,2 and have
succeeded for the first time in syntheses of free acid forms of
PCB (1)2b,c and PΦB2d possible to assemble with the apoproteins.
In this paper, we wish to report the extremely efficient
method for the preparation of B- and C-rings components of phy-
cobilin derivatives and its application to the syntheses of several
phycobilins (Figure 1) useful to investigate the substituent effect
After treating the lactones (10a,b) with sodium allyloxide or
methoxide in the corresponding alcohols at room temperature, the
resulting crude ω-hydroxy esters (11a-d) were oxidized by PCC
in CH2Cl2 at room temperature to afford the corresponding 4-
oxobutanoates (12a,c) or 5-oxopentanoates (12b,d) as listed in
Table 1. In the case of 5-membered lactone 10a, it was necessary
to use excess amounts of alkoxide to obtain 11a,c in reproducible
good yields (Runs 2 and 5), probably due to the existence of equi-
librium going back to the starting lactone 10a.
of chromophores on the function of the reconstituted
holoproteins,1 namely, PCB (1) and its derivatives having
butanoic acid side chain(s) instead of propanoic one(s) (2-4),
regioselectively monoesterified PCB derivatives at C8 or C12
(5,6),3 and regioisomers of PCB with respect to methyl and
propanoic acid substituents of B- and C-rings (7-9) for the struc-
ture/function analysis of phytochrome.
The aldehydes 12a-d thus prepared were next reacted with
nitroethane in the presence of a base to afford the nitroalcohols
13a-d, which were further converted to the corresponding
pyrroles 15a-d. The pyrroles 15a-d were then converted to
ylides 17a-c as B-ring via 16a-c or α-formyl derivatives 18a-c
as C-ring by Vilsmeier-Haack reaction in high yields as report-
Copyright © 2000 The Chemical Society of Japan

Chemistry Letters 2000
493
ed previously (Scheme 2).2b
with decarboxylated C/D-rings (25a-d), available from 23a-d by
treating with TFA, to construct the corresponding tetrapyrrole
intermediates 1'–9', whose structures were fully characterized by
spectroscopic methods.
Finally, three or two (for 5', 6') allyl ester groups of 1'–9'
were deprotected all at once with excess amounts of morpholine
in the presence of palladium catalyst, followed by treatment with
TFA to afford PCB (1) and its derivatives 2-9 by decarboxylation
at C5 as single isomers with all-Z, all-syn conformations5 (con-
firmed by NOESY).
Now, we could have various kinds of PCB derivatives with
free acid forms in hand. Investigations on the reconstituted
chromoproteins using these phycobilins are in progress to
reveal the substituent effect on the function of the holoproteins.
In a similar manner, regioisomers (17d and 18d) of 17a
and 18a were prepared starting from allyl 4-nitrobutanoate and
acetaldehyde through pyrrole 19 (Figure 2).
The present work was financially supported in part by
Grant-in-Aid for Scientific Research from the Ministry of
Education, Science, Sports, and Culture.
References and Notes
1
2
3
W. Rüdiger and F. Thümmler, Angew. Chem., Int. Ed. Engl., 30,
1216 (1991); M. Furuya and P.-S. Song, “Assembly and Properties
of Holophytochrome,” in “Photomorphogenesis in Plants,” 2nd ed,
ed by R. E. Kendrick and G. H. M. Kronenberg, Kluwer Academic
Publishers, Dordrecht, The Netherlands (1994), Chap. 4.3, pp. 105-
140; M. Stanek and K. Grubmayr, Chem. Eur. J. 4, 1653 and 1660
(1998). See also the references cited therein.
a) K. Kohori, M. Hashimoto, H. Kinoshita, and K. Inomata, Bull.
Chem. Soc. Jpn., 67, 3088 (1994). b) T. Kakiuchi, H. Kato, K. P.
Jayasundera, T. Higashi, K. Watabe, D. Sawamoto, H. Kinoshita,
and K. Inomata, Chem. Lett., 1998, 1001. c) K. P. Jayasundera, H.
Kinoshita, and K. Inomata, Chem. Lett., 1998, 1227. d) T. Kakiuchi,
H. Kinoshita, and K. Inomata, Synlett, 1999, 901. See also the refer-
ences cited therein.
When both carboxyl groups were methylated, the chromophore liga-
tion and photochromism were inhibited. Although it was found that
PCB monomethyl ester formed the covalent adduct with apoprotein,
but without photochromism, regiochemistry of the PCB monomethyl
ester used there was ambiguous: S. H. Bhoo, T. Hirano, H.-Y. Jeong,
J.-G. Lee, M. Furuya, and P.-S. Song, J. Am. Chem. Soc., 119, 11717
(1997).
B- and C-Rings (17a-d and 18a-d) were coupled with A-ring
(20) and D-ring (21), respectively, to afford the corresponding A/B-
and C/D-ring components (22a-d and 23a-d) according to our
previous methods2b in good yields as shown in Scheme 3. A/B-
Rings (22a-d) were converted to formyl derivatives (24a-d) by
treatment with methyl orthoformate in TFA, followed by coupling
4
5
M. A. Drian and T. D. Lash, J. Heterocycl. Chem., 31, 255 (1994).
Spectral data of the final products 1-9 are given for UV/Vis (MeOH)
λmax and HRMS (FAB) (M++1) in the following. 1: 364 (49500),
619 (16100) nm; Found: m/z 587.2873. Calcd for C33H39N4O6:
587.2870. 2: 364 (46500), 622 (15700) nm; Found: m/z 601.3026.
Calcd for C34H41N4O6: 601.3026. 3: 364 (45600), 624 (14900) nm;
Found: m/z 601.3026. Calcd for C34H41N4O6: 601.3026. 4: 365
(41200), 623 (13400) nm; Found: m/z 615.3184. Calcd for
C35H43N4O6: 615.3185. 5: 363 (44800), 619 (14800) nm; Found:
m/z 601.3026. Calcd for C34H41N4O6: 601.3026. 6: 364 (51,400),
620 (16900) nm; Found: m/z 601.3019. Calcd for C34H41N4O6:
601.3026. 7: 364 (38100), 624 (12700) nm; Found: m/z 587.2876.
Calcd for C33H39N4O6: 587.2870. 8: 363 (47600), 622 (16300) nm;
Found: m/z 587.2862. Calcd for C33H39N4O6: 587.2870. 9: 363
(37700), 622 (13300) nm; Found: m/z 587.2859. Calcd for
C33H39N4O6: 587.2870.