Convenient Approach to Access Octa-Glycosylated Porphyrins via “Click Chemistry”

Okada, Misako; Kishibe, Yuko; Ide, Kanako; Takahashi, Toshiyuki; Hasegawa, Teruaki

doi:https://doi.org/10.1155/2009/305276

International Journal of Carbohydrate Chemistry

On this page

Abstract Introduction Results and Discussion Conclusion Experimental References Copyright Related Articles

Research Article | Open Access

Volume 2009 | Article ID 305276 | https://doi.org/10.1155/2009/305276

Convenient Approach to Access Octa-Glycosylated Porphyrins via “Click Chemistry”

Misako Okada,¹Yuko Kishibe,¹Kanako Ide,¹Toshiyuki Takahashi,¹and Teruaki Hasegawa^1,2

Academic Editor: Yuan Chuan Lee

Received09 Jun 2009

Revised12 Aug 2009

Accepted04 Sept 2009

Published09 Dec 2009

Abstract

Easy, quantitative, and one-pot introduction of eight -lactoside-modules onto a porphyrin-core was achieved through -catalyzed chemoselective coupling (click chemistry) between a porphyrin carrying eight alkyne-terminals and -lactosyl azides. The obtained porphyrin-based glycocluster shows not only good water-solubility but also strong/specific lectin-affinity.

1. Introduction

Porphyrin and their derivatives are ubiquitous in nature as essential components of various bio-macromolecules, such as hemoglobin and cytochromes, and various porphyrin-based artificial materials have been developed so far for optical, electrical, chemical, and therapeutic purposes [1–7]. In the potential applications of the artificial porphyrins, the porphyrin-based photodynamic therapeutic (PDT) systems are of quite interest, since porphyrins are nontoxic under dark condition and efficient photosensitizer to produce singlet oxygen (¹O₂) [8–13]. The porphyrin-based PDT photosensitizers, however, include some obstacles: that is, their low water solubility and no cell specificity.

To overcome these problems, various porphyrin derivatives having carbohydrate-appendages (glycoporphyrins) have been developed so far [14–22]. Since carbohydrates have many hydroxy groups and the resultant excellent water solubility, introduction of carbohydrate units is expected to improve the water solubility of porphyrin derivatives. Since increasing number of introduced carbohydrate units should result in further improvement of the water solubility, porphyrin-derivatives having multiple carbohydrate-appendages (glycoclusters: the number of introduced carbohydrate units is usually up to 4 in the case of porphyrins) have been developed by many research groups. However, these limited numbers of carbohydrate-appendages still cannot compensate hydrophobicity of porphyrins and only few examples of water-soluble glycoporphyrin have been reported so far. To increase water solubility of the glycoporphyrins, much larger number of carbohydrate units should be introduced into porphyrin scaffolds.

In addition to the increasing water-solubility, introduction of carbohydrate units has another aspect, that is, enhanced cell specificity. It is now well known that carbohydrates exist as components of glycoproteins and glycolipids on cell surfaces and play substantial roles in various molecular recognition events (fertilization, differentiation, cell-cell adhesion, etc.) via specific carbohydrate-protein interactions [23–25]. Many researchers have studied the carbohydrate-protein interactions and revealed that clustered, or multivalent, carbohydrates interact with carbohydrate-binding proteins in a stronger and more specific manner than monomeric carbohydrates do [26]. This phenomenon is now widely recognized as carbohydrate cluster effect and various artificial compounds having clustered carbohydrates have been developed so far [27–32]. For example, oligosaccharide-appended polystyrene is commercially available as a coating reagent of polystyrene dishes for hepatocyte cultivation [33, 34] and oligosaccharide-appended cyclodextrins/cyclophanes are developed as cell-specific drug carriers [35–39]. The porphyrin derivatives having multivalent carbohydrates should, therefore, acquire both well water solubility and excellent cell specificity.

As mentioned earlier, much larger number of carbohydrate units should be introduced into porphyrin scaffolds to increase their water solubility and cell specificity. This strategy, however, also increases synthetic difficulty. Synthetic strategy to access glycoporphyrins can be divided into two categories: (1) cyclization of glycosylated benzaldehydes [14–19] and (2) glycosylation of porphyrins [20–22] (Figure 1). In the first strategy, benzaldehyde derivatives having carbohydrate-appendages are synthesized and then coupled with pyrrole to be cyclized into the corresponding glycoporphyrins. This strategy suffers from low yields in the cyclization step owing to steric hindrance of carbohydrate-appendages. Larger number of introduced carbohydrates results in enhanced steric hindrance and the resultant lower yields. On the other hand, the later strategy includes cyclization of benzaldehyde having reaction points (hydroxy-, carboxy-, haloalkyl-groups, etc.) and the following multiglycosylation onto the multiple reaction points. This strategy is free from the steric hindrance in the cyclyzation step, but one-pot introduction of a large number of carbohydrate units also suffers from low total coupling yields. To develop easy, general, and quantitative strategy for introducing multiple copies of carbohydrate units is essential to establish practical PDT systems.

Recently, Cu⁺-catalyzed chemoselective couplings between organic azides and terminal alkynes have attracted increasing research interest owing to its convenient, quick, and quantitative reaction [40–42]. This chemoselective coupling is now, therefore, recognized as “click chemistry” and is used for various applications including chemical modifications of self-assembled monolayers (SAMs), ligation between polymer strands, and so forth [43–45]. These excellent works encouraged us to establish an easy two-step strategy based on the click chemistry for one-pot introduction of large number of carbohydrate units into porphyrin scaffolds: (1) synthesis of porphyrins carrying multiple but small alkyne-terminals and (2) chemoselective and quantitative introduction of sugar azide onto the porphyrins. Since the click chemistry is highly chemoselective and tolerant for various reaction media, this approach should accelerate the development of glycoporphyrin library to establish practical porphyrin-based photosensitizers. We, herein, report not only synthetic details of octa--lactosylated porphyrin but also its water solubility, spatial structure, and lectin affinity.

2. Results and Discussion

The porphyrin core having eight alkyne-terminals was synthesized from 3,5-dihydroxy-benzaldehyde via Williamson coupling with propargyl bromide and the subsequent Lindsey condensation with pyrrole (Scheme 1). The introduction of eight -lactoside modules was attained by treating the porphyrin core with -lactosyl azide in DMSO-containing CuBr₂, ascorbic acid, and propylamine. After dialysis (water, MWCO500) followed by lyophilization, octa--lactosylated porphyrinato-copper (PorCu-Lac₈) was obtained as brownish purple powder. We firstly tried to obtain the chemical evidence through NMR measurements, ¹H NMR spectrum of PorCu-Lac₈ was, however, too noisy to be assignable, possibly owing to its insufficient solubility in pure D₂O and/or the magnetic property of inserted Cu²⁺. The chemical evidence was, therefore, obtained from MALDI-TOF-MS showing a predominant peak at 4045.13 ([M+Na]⁺, calc. 4045.23 for PorCu-Lac₈, Figure 2(a)). No peak assignable to porphyrins having smaller numbers of -lactoside-appendage (by-products resulting from incomplete coupling) was observed in the spectrum. These spectral data clearly indicate that the porphyrin having eight alkyne-terminals is quantitatively converted into PorCu-Lac₈. Such quantitative introduction of carbohydrate-modules onto presynthesized porphyrin was never obtained through the conventional coupling strategies, such as amide- and ether-couplings. We would like to also to emphasize the great advantage of this strategy; that is, the simple dialysis of the reaction mixture is enough to produce the porphyrin having large number of carbohydrate-appendages in a chemically pure form.

(a)

(b)

We also tried to support this quantitative conversion through chromatographic analysis of the product. The RP-HPLC analysis of PorCu-Lac₈, however, gave multiple broad peaks, possibly arising from the aggregation of PorCu-Lac₈ in the HPLC condition. We, therefore, carried out per acetylation of PorCu-Lac₈ and the per acetylated PorCu-Lac₈ was analyzed on RP-HPLC column. As shown in Figure 2(b), one main peak (c) along with two minor peaks (a) and (b) is observed in the RP-HPLC chart, supporting the high conversion yield.

Through this chemoselective coupling, insertion of Cu²⁺ into the porphyrin ring was simultaneously occurred and no peak assignable to the corresponding free-base porphyrin carrying eight -lactoside-appendages was observed. To clarify which process (i.e., coupling or insertion) firstly occurs, we again carried out the same coupling reaction with 0.2 eq. of CuBr₂. The MALDI-TOF-MS analysis of the product showed two peaks assignable to the substrate and Cu²⁺-inserted substrate, respectively, and no peak assignable to PorCu-Lac⁸ was observed. These data indicate that the Cu²⁺ is firstly consumed by insertion reaction, and then excess Cu²⁺ is reduced by ascorbic acid to catalyze the coupling reaction.

To elucidate water solubility of PorCu-Lac₈, we measured its UV-vis spectra in water/DMSO mixed solvent system with various water contents. As shown in Figure 3, PorCu-Lac₈ showed sharp Soret-band peak at 422 nm in DMSO-rich solvent system (water = 2.0% v/v), indicating the single molecular dispersion of PorCu-Lac₈. Although the UV-vis spectrum of PorCu-Lac₈ remains unchanged when water contents are below 50%, intensity of the Soret band gradually decreases with an increasing water-content when water content is above 50%, and a new peak attributable to H-aggregated PorCu-Lac₈ simultaneously appears at 405 nm. We would like to, however, emphasize that the original peak arising from monomeric PorCu-Lac₈ is still observed even in pure water, indicating good water solubility of PorCu-Lac₈. This water solubility of PorCu-Lac₈ should arise from eight -lactoside-appendages introduced onto metapositions that form a thick hydrophilic shell structure to effectively shield the hydrophobic surface of porphyrin-core. (We also synthesized another octa--lactosylated porphyrin with a different spacer structure through the Cu⁺-catalyzed coupling between porphyrin having eight azide-terminals and propargyl -lactoside. Although this compound was used to investigate whether structural variation at the spacer moiety has any affects on properties (water solubility and lectin affinity) of glycosylated porphyrins, negligible differences can be observed between the properties of these two octa--lactosylated porphyrins (data now shown)).

(a)

(b)

To confirm our assumption, we synthesized a porphyrin derivative having four -lactoside-appendages (PorCu-Lac₄), in which each -lactoside-appendage is attached onto paraposition of phenyl-appendages. Although this tetraglycosylated analogue is also well soluble in DMSO, an addition of only small amount of water induces strict broadening and blue-shift of Soret band of its UV-vis spectrum, suggesting its strong aggregation via hydrophobic interactions between the exposed porphyrin cores.

Atomic force microscopic (AFM) images of PorCu-Lac₈ cast from aqueous solution onto mica substrates also strongly support its good water-solubility. As shown in Figure 4(a), dot-like objects having a similar diameter are observed in the AFM images. No extremely large-dot arising from the porphyrin aggregates was observed, showing the good solubility of PorCu-Lac₈ in aqueous media. It should be noted that cross section profiles of the dot-like objects (Figures 4(b) and 4(c)) have height of ca. 2 nm with trapezoidal or hollow shapes. This unique trapezoidal/hollow shape resembles the spatial structure of PorCu-Lac₈ having thin porphyrin center and bulky carbohydrate-periphery, supporting that the each dot-like object observed in AFM images is arising from single PorCu-Lac₈ molecule.

Spatial structure of PorCu-Lac₈ was also assessed in detail through molecular dynamics (MD) calculation. The molecule was constructed and then, dynamics (100 000 steps, CHARMm, 300 K, NVT, GBSW solvent model) was carried out after minimization, heating, and equilibration processes. The most stable conformation during the dynamics process is shown in Figure 5, in which PorCu-Lac₈ takes spherical structure with the porphyrin-core embedded into the densely packed carbohydrate shell. This closely packed carbohydrate-appendages should effectively shield the hydrophobic porphyrin-core from the media and then, improve the water solubility of PorCu-Lac₈.

Lectin-affinity of PorCu-Lac₈ was assessed based on the fluorescence titration assay using fluorescein isothiocyanate (FITC)-labeled lectins (Figure 6). Fluorescent intensity of FITC-RCA₁₂₀ (Recinus comunus agglutinin, Lac-specific) was suppressed by addition of PorCu-Lac₈, and the dissociation constant was estimated to M by computational curve fitting, indicating their strong binding. On the other hand, no such fluorescence spectral change was observed for FITC-ConA (Concanavalin A, α-Glc/Man-specific). These fluorescent spectroscopic data indicate strong and specific lectin-affinity of PorCu-Lac₈. The well-shielded porphyrin core of PorCu-Lac₈ is also important for its specific lectin-affinity: that is, PorCu-Lac₄ having an exposed hydrophobic porphyrin core interacts with not only RCA₁₂₀ but also ConA in nonspecific manner, presumably owing to hydrophobic interaction with hydrophobic protein residues.

(a)

(b)

3. Conclusion

We established easy and quick strategy toward multiglycosylated porphyrins by using click chemistry. Through this strategy, not only the Cu⁺-catalyzed introduction of multiple oligosaccharide units but also the insertion of Cu²⁺ into the porphyrin scaffold was simultaneously occurs. Porphyrinatocopper derivatives have, however, poor singlet oxygen productivity and, therefore, are not suitable for PDT photosensitizers. Our research effort is now paid to a metallation of the porphyrin having eight alkyne-terminals by Zn²⁺ prior to the Cu⁺-catalyzed introduction of oligosaccharide units. The resultant porphyrinatozinc-based glycoclusters would be easily converted by treating with dilute acids into the corresponding free base porphyrins with high singlet oxygen productivity. The results will be reported elsewhere in due course.

4. Experimental

4.1. General

1H and 13C NMR spectra were acquired on a JEOL AL300 (JEOL DATUM, Ltd) in CDCl3 at 300 MHz. The chemical shifts were reported in ppm () relative to Me4Si. IR spectra were recorded on a JASCO FT/IR-4100 Fourier transform infrared spectrometer (JASCO Co., Ltd). Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectra were recorded on SHIMAZU AXIMA-CFR+ (SHIMAZU, Ltd). Fluorescence spectra were recorded on FP-6200 spectrofluorometer (JASCO, Co. Ltd.). Atomic force microscopic (AFM) images were acquired on SII Nanonavi E-sweep (SII nanotechnology, Inc.) using SI-DF40 as a cantilever. Molecular dynamic calculation was carried out on Discover Studio 2.1 (Accerlys Software Inc.). Silica gel 60 N (particle size 63–210 m) for column chromatography was purchased from KANTO CHEMICAL Co., INC. Thin layer chromatography (TLC) was carried out with Merck TLC aluminum sheets precoated with silica gel 60 F254. All other chemicals were purchased from Wako Pure Chemical Industries Ltd. or Kishida Chemicals Co. Ltd.

4.2. Synthesis of 3,5-Dipropargyloxy-Benzaldehyde

However, 3,5-Dihydroxy-benzaldehyde (0.10 g, 0.74 mmol) and K2CO3 (3.5 g, 25 mmol) were added to -dimethylformamide (DMF) and then the resultant mixture was stirred at 60°C for 30 minutes. After cooling down to the ambient temperature, propargyl bromide (0.26 g, 2.2 mmol) was added and the reaction mixture was stirred for overnight. The resultant mixture was diluted with ethyl acetate and washed with water and NaCl-saturated water several times. The organic layer was dried over anhydrous MgSO4, filtered, and concentrated to dryness to obtain 3,5-dipropargyloxy-benzaldehyde as white powder in 42% yield: [M+H]+ = 215.12 (calc. 215.06); 1H NMR (CDCl3, TMS): 9.92 (s, 1H), 7.14 (d, Hz, 2H), 6.88 (t, Hz, 1H), 4.74 (d, Hz, 4H), 2.56 (t, Hz, 2H); 13C NMR (CDCl3, TMS): 191.503, 159.105, 138.377, 108.732, 78.122, 77.208, 76.235.

4.3. Synthesis of 5,10,15,20-Tetra--Dipropargyloxyphenyl-Porphyrin

To 3,5-dipropargyloxy-benzaldehyde (67 mg) and pyrrole (21 mg) in dry CH2Cl2 (200 mL), trifluoroacetic acid (30 L) was added. The stirring was continued for 15 hours at room temperature and then -chloranil (92 mg) was added. After additional 1 hour stirring, triethylamine (65 L) was added and the resulting mixture was evaporated to dryness. Insoluble materials were separated through silica-gel-packed column using chloroform as an eluent. The fractions were combined, evaporated, and purified by chromatography on a silica-gel column (30 cm long; 3 cm i.d.; hexane-ethyl acetate = in v/v) to give 5,10,15,20-tetra--dipropargyloxyphenyl-porphyrin as a purple powder (7.9%): [M+Na]+ = 1048.88 (calc. 1048.11); 1H NMR (CDCl3, TMS): 8.96 (s, 8H), 7.52 (d, Hz, 8H), 7.07 (t, Hz, 4H), 4.86 (d, Hz, 16H), 2.60 (t, Hz, 8H), 2.87 (brs, 2H); 13C NMR (CDCl3, TMS): 156.805, 144.028, 131.133, 119.413, 115.343, 102.205, 78.394, 77.216, 75.988, 56.224.

4.4. Synthesis of Porphyrinatocopper Having Eight -Lactoside Appendages (PorCu-Lac₈)

However, 5,10,15,20-Tetra--dipropargyloxyphenyl-porphyrin (10 mg), -lactosyl-azide (68 mg), CuBr2 (5.0 mg), ascorbic acid (6.0 mg), -propylamine (1.0 mg) were added into DMSO in small vessel and the resultant reaction mixture was kept at room temperature for overnight. The resultant mixture was dialyzed (MWCO500, water) and lyophilized to give PorCu-Lac8 as brownish purple powder in 14.6% yield: [M+Na]+ = 4045.13 (calc. 4045.23); IR (KBr, cm-1) 2970.73 (OH).

Acknowledgment

This work was partially supported by Grant-in-Aid for Scientific Research (no. 18750103) from the Ministry of Education, Culture, Sports, Science and Technology, Japan.

References

A. Satake and Y. Kobuke, “Artificial photosynthetic systems: assemblies of slipped cofacial porphyrins and phthalocyanines showing strong electronic coupling,” Organic and Biomolecular Chemistry, vol. 5, no. 11, pp. 1679–1691, 2007.
View at: Publisher Site | Google Scholar
J. Králová, J. Koivukorpi, Z. Kejik et al., “Porphyrin-bile acid conjugates: from saccharide recognition in the solution to the selective cancer cell fluorescence detection,” Organic and Biomolecular Chemistry, vol. 6, no. 9, pp. 1548–1552, 2008.
View at: Publisher Site | Google Scholar
S. Paul, F. Amalraj, and S. Radhakrishnan, “CO sensor based on polypyrrole functionalized with iron porphyrin,” Synthetic Metals, vol. 159, no. 11, pp. 1019–1023, 2009.
View at: Publisher Site | Google Scholar
C. Zhang and K. S. Suslick, “Syntheses of boronic-acid-appended metalloporphyrins as potential colorimetric sensors for sugars and carbohydrates,” Journal of Porphyrins and Phthalocyanines, vol. 9, no. 9, pp. 659–666, 2005.
View at: Google Scholar
D. Mykhaylo, S. David, L. Kamil et al., “Steroid–porphyrin conjugate for saccharide sensing in protic media,” Organic & Biomolecular Chemistry, vol. 1, pp. 3458–3463, 2003.
View at: Google Scholar
O. Hirata, Y. Kubo, M. Takeuchi, and S. Shinkai, “Mono- and oligosaccharide sensing by phenylboronic acid-appended 5,15-bis(diarylethynyl)porphyrin complexes,” Tetrahedron, vol. 60, no. 49, pp. 11211–11218, 2004.
View at: Publisher Site | Google Scholar
F.-C. Gong, D.-X. Wu, Z. Cao, and X.-C. He, “A fluorescence enhancement-based sensor using glycosylated metalloporphyrin as a recognition element for levamisole assay,” Biosensors and Bioelectronics, vol. 22, no. 3, pp. 423–428, 2006.
View at: Publisher Site | Google Scholar
K. Davia, D. King, Y. Hong, and S. Swavey, “A porphyrin-ruthenium photosensitizer as a potential photodynamic therapy agent,” Inorganic Chemistry Communications, vol. 11, no. 5, pp. 584–586, 2008.
View at: Publisher Site | Google Scholar
Y.-J. Ko, K.-J. Yun, M.-S. Kang et al., “Synthesis and in vitro photodynamic activities of water-soluble fluorinated tetrapyridylporphyrins as tumor photosensitizers,” Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 10, pp. 2789–2794, 2007.
View at: Publisher Site | Google Scholar
K. Davia, D. King, Y. Hong, and S. Swavey, “A porphyrin-ruthenium photosensitizer as a potential photodynamic therapy agent,” Inorganic Chemistry Communications, vol. 11, no. 5, pp. 584–586, 2008.
View at: Publisher Site | Google Scholar
H. M. Wang, J. Q. Jiang, J. H. Xiao, R. L. Gao, F. Y. Lin, and X. Y. Liu, “Porphyrin with amino acid moieties: a tumor photosensitizer,” Chemico-Biological Interactions, vol. 172, no. 2, pp. 154–158, 2008.
View at: Publisher Site | Google Scholar
S. Patachia, R. Ion, S. Varga, and M. Rinja, “Porphyrin encapsulation in nanostructured hydrogels,” Journal of Optoelectronics and Advanced Materials, vol. 9, no. 6, pp. 1816–1820, 2007.
View at: Google Scholar
M. G. Alvarez, F. Príncipe, M. E. Milanesio, E. N. Durantini, and V. Rivarola, “Photodynamic damages induced by a monocationic porphyrin derivative in a human carcinoma cell line,” International Journal of Biochemistry and Cell Biology, vol. 37, no. 12, pp. 2504–2512, 2005.
View at: Publisher Site | Google Scholar
O. Gaud, R. Granet, M. Kaouadji, P. Krausz, J. C. Biais, and G. Bolbach, “Synthèse et analyse structurale de nouvelles mèso-arylporphyrines glycosylèes en vue de l'application en photothèrapie des cancers,” Canadian Journal of Chemistry, vol. 74, no. 4, pp. 481–499, 1996.
View at: Google Scholar
V. Carré, O. Gaud, I. Sylvain et al., “Fungicidal properties of meso-arylglycosylporphyrins : influence of sugar substituents on photoinduced damage in the yeast Saccharomyces cerevisiae,” Journal of Photochemistry and Photobiology B, vol. 48, no. 1, pp. 57–62, 1999.
View at: Publisher Site | Google Scholar
V. Sol, V. Chaleix, Y. Champavier, R. Granet, Y.-M. Huang, and P. Krausz, “Glycosyl bis-porphyrin conjugates: synthesis and potential application in PDT,” Bioorganic and Medicinal Chemistry, vol. 14, no. 23, pp. 7745–7760, 2006.
View at: Publisher Site | Google Scholar
B. D. Stasio, C. Frochot, D. Dumas et al., “The 2-aminoglucosamide motif improves cellular uptake and photodynamic activity of tetraphenylporphyrin,” European Journal of Medicinal Chemistry, vol. 40, no. 11, pp. 1111–1122, 2005.
View at: Publisher Site | Google Scholar
M. Amessou, D. Carrez, D. Patin et al., “Retrograde delivery of photosensitizer ${(TPPp-O- ß -GluOH)}_{3}$ selectively potentiates its photodynamic activity,” Bioconjugate Chemistry, vol. 19, no. 2, pp. 532–538, 2008.
View at: Publisher Site | Google Scholar
S. Hirohara, M. Obata, H. Alitomo et al., “Structure-photodynamic effect relationships of 24 glycoconjugated photosensitizers in HeLa cells,” Biological and Pharmaceutical Bulletin, vol. 31, no. 12, pp. 2265–2272, 2008.
View at: Publisher Site | Google Scholar
D. Oulmi, P. Maillard, J.-L. Guerquin-Kern, C. Huel, and M. Momenteau, “Glycoconjugated porphyrins. 3. Synthesis of flat amphiphilic mixed meso-(glycosylated aryl)arylporphyrins and mixed meso-(glycosylated aryl)alkylporphyrins bearing some mono- and disaccharide groups,” Journal of Organic Chemistry, vol. 60, no. 6, pp. 1554–1564, 1995.
View at: Google Scholar
S. Hirohara, M. Obata, H. Alitomo et al., “Synthesis and photocytotoxicity of S-glucosylated 5,10,15,20- tetrakis(tetrafluorophenyl)porphyrin metal complexes as efficient 1 $O_{2}$ -generating glycoconjugates,” Bioconjugate Chemistry, vol. 20, no. 5, pp. 944–952, 2009.
View at: Publisher Site | Google Scholar
S. Thompson, X. Chen, L. Hui, A. Toschi, D. A. Foster, and C. M. Drain, “Low concentrations of a non-hydrolysable tetra-S-glycosylated porphyrin and low light induces apoptosis in human breast cancer cells via stress of the endoplasmic reticulum,” Photochemical and Photobiological Sciences, vol. 7, no. 11, pp. 1415–1421, 2008.
View at: Publisher Site | Google Scholar
M. Fukuda and O. Hindsgaul, Molecular and Cellular Glycobiology, Oxford University Press, Oxford, UK, 2000.
A. Varki, R. D. Cummings, and J. D. Esko, Essentials of Glycobiology, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, USA, 2008.
B. O. Fraser-Reid, K. Tatsuta, and J. Thiem, Glycoscience–Chemistry and Chemical Biology I-III, Springer, Berlin, Germany, 2008.
M. Mammen, M. S.-K. Choi, and J. M. Whitesides, “Polyvalent interactions in biological systems: implications for design and use of multivalent ligands and inhibitors,” Angewandte Chemie International Edition, vol. 37, no. 20, pp. 2754–2794, 1998.
View at: Google Scholar
X. Jiang, M. Ahmed, Z. Deng, and R. Narain, “Biotinylated glyco-functionalized quantum dots: synthesis, characterization, and cytotoxicity studies,” Bioconjugate Chemistry, vol. 20, no. 5, pp. 994–1001, 2009.
View at: Publisher Site | Google Scholar
A. W. Kawaguchi, H. Okawa, and K. Hashimoto, “Synthesis of glycopolymers bearing mannaric pendants as inhibitors on the $β$ -glucuronidase activity: the inhibition mechanisms of mannaric- and glucaric-compounds,” Journal of Polymer Science, Part A, vol. 47, no. 8, pp. 2032–2042, 2009.
View at: Publisher Site | Google Scholar
C. Xue, S. Velayudham, S. Johnson et al., “Highly water-soluble, fluorescent, conjugated fluorene-based glycopolymers with poly(ethylene glycol)-tethered spacers for sensitive detection of escherichia coli,” Chemistry—A European Journal, vol. 15, no. 10, pp. 2289–2295, 2009.
View at: Publisher Site | Google Scholar
Y. Miura, K. Yamamoto, K. Yasuda, Y. Nishida, and K. Kobayashi, “Inhibition of alzheimer amyloid aggregation with sulfate glycopolymers,” Advances in Science and Technolog, vol. 57, pp. 166–169, 2008.
View at: Google Scholar
T. Hasegawa, T. Fujisawa, M. Numata et al., “Schizophyllans carrying oligosaccharide appendages as potential candidates for cell-targeted antisense carrier,” Organic and Biomolecular Chemistry, vol. 2, no. 21, pp. 3091–3098, 2004.
View at: Publisher Site | Google Scholar
J. Xue, Y. Pan, and Z. Guo, “Neoglycoprotein cancer vaccines: synthesis of an azido derivative of GM3 and its efficient coupling to proteins through a new linker,” Tetrahedron Letters, vol. 43, no. 9, pp. 1599–1602, 2002.
View at: Publisher Site | Google Scholar
M. Goto, Y. Makino, K. Kobayashi, C.-S. Cho, and T. Akaike, “Hepatocyte attachment onto thermosensitive $\to$ 4)-D-gluconamide),” Journal of Biomaterials Science, Polymer Edition, vol. 12, no. 7, pp. 755–768, 2001.
View at: Publisher Site | Google Scholar
H. Yura, M. Goto, H. Okazaki, K. Kobayashi, and T. Akaike, “Structural effect of galactose residue in synthetic glycoconjugates on interaction with rat hepatocytes,” Journal of Biomedical Materials Research, vol. 29, no. 12, pp. 1557–1565, 1995.
View at: Publisher Site | Google Scholar
Y. Oda, N. Kobayashi, T. Yamanoi, K. Katsuraya, K. Takahashi, and K. Hattori, “ $β$ -cyclodextrin conjugates with glucose moieties designed as drug carriers: their syntheses, evaluations using concanavalin A and doxorubicin, and structural analyses by NMR spectroscopy,” Medicinal Chemistry, vol. 4, no. 3, pp. 244–255, 2008.
View at: Publisher Site | Google Scholar
A. Vargas-Berenguel, F. Ortega-Caballero, and J. M. Casas-Solvas, “Supramolecular chemistry of carbohydrate clusters with cores having guest binding abilities,” Mini-Reviews in Organic Chemistry, vol. 4, no. 1, pp. 1–14, 2007.
View at: Publisher Site | Google Scholar
J. M. G. Fernandez, C. O. Mellet, and J. Defaye, “Glyconanocavities: cyclod- extrins and beyond,” Journal of Inclusion Phenomena and Macrocyclic Chemistry, vol. 56, pp. 149–159, 2006.
View at: Google Scholar
O. Hayashida and D. Sato, “Preparation and multivalently enhanced guest-binding affinity of water-soluble cyclophane heptadecamers,” Journal of Organic Chemistry, vol. 73, no. 8, pp. 3205–3211, 2008.
View at: Publisher Site | Google Scholar
Y. Oda, M. Miura, K. Hattori, and T. Yamanoi, “Syntheses and doxorubicin-inclusion abilities of $β$ -cyclodextrin derivatives with a hydroquinone $α$ -glycoside residue attached at the primary side,” Chemical & Pharmaceutical Bulletin, vol. 57, pp. 74–78, 2009.
View at: Google Scholar
L. V. Lee, M. L. Mitchell, S.-J. Huang, V. V. Fokin, K. B. Sharpless, and C.-H. Wong, “A potent and highly selective inhibitor of human $α$ -1,3-fucosyltransferase via click chemistry,” Journal of the American Chemical Society, vol. 125, no. 32, pp. 9588–9589, 2003.
View at: Publisher Site | Google Scholar
C. W. Tornøe and M. Meldal, “Peptidotriazoles: copper(I)-catalyzed 1,3-dipolar cycloadditions on solid-phase,” in Proceedings of the 2nd International and the 17th American Peptide Symposium, pp. 263–264, San Diego, Calif, USA, June 2001.
View at: Google Scholar
C. W. Tornøe, C. Christensen, and M. Meldal, “Peptidotriazoles on solid phase: [1,2,3]-triazoles by regiospecific copper(I)-catalyzed 1,3-dipolar cycloadditions of terminal alkynes to azides,” Journal of Organic Chemistry, vol. 67, no. 9, pp. 3057–3064, 2002.
View at: Publisher Site | Google Scholar
M. C. Bryan, F. Fazio, H.-K. Lee et al., “Covalent display of oligosaccharide arrays in microtiter plates,” Journal of the American Chemical Society, vol. 126, no. 28, pp. 8640–8641, 2004.
View at: Publisher Site | Google Scholar
B. Helms, J. L. Mynar, C. J. Hawker, and J. M. J. Fréchet, “Dendronized linear polymers via “click chemistry”,” Journal of the American Chemical Society, vol. 126, no. 46, pp. 15020–15021, 2004.
View at: Publisher Site | Google Scholar
J. A. Opsteen and J. C.M. van Hest, “Modular synthesis of block copolymers via cycloaddition of terminal azide and alkyne functionalized polymers,” Chemical Communications, no. 1, pp. 57–59, 2005.
View at: Publisher Site | Google Scholar

Copyright

Copyright © 2009 Misako Okada et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

PDF Download Citation

Download other formats

Order printed copies

Views

1682

Downloads

794

Citations

International Journal of Carbohydrate Chemistry

Convenient Approach to Access Octa-Glycosylated Porphyrins via “Click Chemistry”

Abstract

1. Introduction

2. Results and Discussion

3. Conclusion

4. Experimental

4.1. General

4.2. Synthesis of 3,5-Dipropargyloxy-Benzaldehyde

4.3. Synthesis of 5,10,15,20-Tetra- -Dipropargyloxyphenyl-Porphyrin

4.4. Synthesis of Porphyrinatocopper Having Eight -Lactoside Appendages (PorCu-Lac8)

Acknowledgment

References

Copyright

4.3. Synthesis of 5,10,15,20-Tetra--Dipropargyloxyphenyl-Porphyrin

4.4. Synthesis of Porphyrinatocopper Having Eight -Lactoside Appendages (PorCu-Lac₈)