synthesis of boronated derivatives of pheophorbide a

ISSN 0012-5008, Doklady Chemistry, 2008, Vol. 423, Part 1, pp. 294–298. © Pleiades Publishing, Ltd., 2008.Original Russian Text © V.A. Ol’shevskaya, A.V. Zaitsev, A.N. Savchenko, E.G. Kononova, P.V. Petrovskii, V.N. Kalinin, 2008, published in Doklady Akademii Nauk, 2008,Vol. 423, No. 3, pp. 345–349.

294

Photodynamic therapy (PDT) [1] and boron neutroncapture therapy (BNCT) [2] are promising clinicalapproaches enabling a local effect on a tumor with littleif any damage to the healthy tissue around it. Both meth-ods are based on the selective accumulation of photo-and radiosensitizer in cancer cells and in situ productionof high-energy particles upon activation of the sensitizer

by light of a definite wavelength (PDT, ) or thermal

neutrons (BNCT,

4

He

2+

and

7

Li

3+

). The particles pro-duced in a tumor have short path lengths comparablewith the cell size, which allows them to locally destroytumor cells (apoptosis, necrosis) leaving healthy tissueintact [3]. Furthermore, PDT used for the treatment of

O2–

Synthesis of Boronated Derivatives of Pheophorbide

a

V. A. Ol’shevskaya, A. V. Zaitsev, A. N. Savchenko, E. G. Kononova,P. V. Petrovskii, and V. N. Kalinin

Presented by Academician O.N. Chupakhin June 10, 2008

Received June 26, 2008

DOI:

10.1134/S0012500808110086

Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, ul. Vavilova 28, Moscow, 119991 Russia

CHEMISTRY

Table 1.

Spectral data for compounds

VIII

–

XVI

Com-pound

IR spectrum,cm

–1

λ

max

, nm (

ε ×

10

–3

)Mass spec-

trum, [M]

+

(

m

/

z

)

VIII

3442 (NH); 3060 (carborane CH); 2587 (BH); 1736 (ester C=O); 1687 (C=O, 13(1)); 1620 (chlorin band)

663 (44.0); 613 (9.2); 577 (9.2);550 (10.1); 426 (159.7)

749

IX


668 (43.0); 613 (9.0); 576 (9.1);550 (10.2); 426 (157.1)

763

X


668 (27); 613 (9.2); 577 (9.2);550 (10.1); 426 (97)

749

XI


669 (8.24); 613 (1.9); 539 (2.2);509 (2.3); 415 (21.9)

749

XII


669 (9.4); 611 (1.9); 539 (2.0);509 (2.2); 413 (20.9)

889

XIII


669 (9.3); 610 (2.1); 539 (2.4);509 (2.2); 413 (20.8)

917

XIV


669 (10.8); 613 (2.0); 539 (2.2);509 (2.7); 415 (23.2)

889

XV


675 (12.4); 612 (1.8); 539 (2.0);509 (2.6); 430 (36.9)

889

XVI

3440 (NH); 2504 (BH); 1735 (ester C=O);1685 (C=O, 13(1)); 1622 (chlorin band)

678 (12.3); 613 (1.7); 540 (2.1);510 (2.7); 429 (38.6)

1153

* IR spectra were obtained on a UR-20 spectrophotometer in KBr pellets. Electron spectra were recorded on a Jasco UV/VIS-7800 spec-trophotometer in CHCl

3

solution. Mass spectra were determined on a Vision-2000 (MALDI) spectrometer.

DOKLADY CHEMISTRY

Vol. 423

Part 1

2008

SYNTHESIS OF BORONATED DERIVATIVES OF PHEOPHORBIDE

a

295

Table 2.

1

H and

11

B NMR spectra of compounds

VIII

–

XVI

Com-pound

1

H (CDCl

3

,

δ

, ppm)

11

B NMR (CDCl

3

,

δ

, ppm)

VIII

9.38 (s, 1H, 10-H); 9.28 (s, 1H, 5-H); 8.53 (s, 1H, 20-H); 7.93 (dd, 1H,

J

= 17.8 and 11.6 Hz, 3(1)-H); 6.24 (dd, 1H,

J

= 17.9 and 1.2 Hz, 3(2)-trans), 6.12 (dd, 1H,

J

= 10.5 and 1.2 Hz, 3(2)-cis); 5.25 (d, 1H,

J

= 19.0 Hz, 13(2)-H); 4.46 (m, 2H, 17-H); 4.27 (m, 1H, 18-H); 3.62 (s, 3H, 12(1)-CH

3

); 3.61 (s, 3H, 17(4)-CH

3

); 3.59 (m, 2H, 8(1)-CH

2

); 3.47 (m, 3H, 2(1)-CH

3

); 3.38 (s, 3H, 7(1)-CH

3

); 3.16 (s, 2H, 13(4)-CH

2

); 2.64 (m, 2H, 17(1)-CH

3

); 2.26 (m, 2H, 17(2)-CH

2

); 2.16 (br s, 1H, carborane CH); 1.80 (d, 3H,

J

= 7.3 Hz, 18(1)-CH

3

); 1.65 (t, 3H, 8(2)-CH

3

); 0.88 (br s, 1H, I-NH); –1.77 (br s, 1H, III-NH)

–2.86 (d, 1B,

J

= 150.2 Hz);–5.15 (d, 1B,

J

= 147.8 Hz);–9.22 (d, 3B,

J

= 150.8 Hz);–11.83 (d, 1B,

J

= 168.5 Hz);–13.23 (s, 4B)

IX

9.46 (s, 1H, 10-H); 9.30 (s, 1H, 5-H); 8.55 (s, 1H, 20-H); 7.93 (dd, 1H,

J

= 17.6 and 11.2 Hz, 3(1)-H); 6.28 (d, 1H,

J

= 18.0 Hz, 3(2)-trans); 6.24 (s, 1H, 13(2)-H); 6.16 (d, 1H,

J

= 18.2 Hz, 3(2)-cis); 4.34 (m, 1H, 18-H); 4.22 (m, 1H, 17-H); 3.68 (s, 3H, 12(1)-CH

3

); 3.64 (c, 3H, 17(4)-CH

3

); 3.61 (m, 2H, 8(1)-CH

2

); 3.59 (s, 3H, 2(1)-CH

3

); 3.39 (s, 3H, 7(1)-CH

3

); 3.18 (s, 4H, 13(4)-CH

2

, 13(5)-CH

2

); 2.64 (br s, 1H, carborane CH); 2.57 (m, 2H, 17(1)-CH

2

); 2.28 (m, 2H, 17(2)-CH

2

); 1.85 (d, 3H,

J

= 7.4 Hz, 18(1)-CH

3

); 1.69 (t, 3H,

J

= 7.0 Hz, 8(2)-CH

3


–2.08 (d, 1B,

J

= 149.0 Hz);–5.37 (d, 1B,

J

= 128.9 Hz);–9.59 (d, 3B,

J

= 153.7 Hz);–11.18 (s, 2B); –12.61(d, 3B,

J

= 180.3 Hz)

X

9.47 (s, 1H, 10-H); 9.31 (s, 1H, 5-H); 8.56 (s, 1H, 20-H); 7.92 (dd, 1H,

J

= 17.8 and 11.6 Hz, 3(1)-H); 6.24 (dd, 1H,

J

= 17.8 and 1.3 Hz, 3(2)-trans); 6.19 (s, 1H, 13(2)-H); 6.12 (dd, 1H,

J

= 11.6 and 1.3 Hz, 3(2)-cis); 4.44 (m, 1H, 17-H); 4.29 (m, 1H, 18-H); 3.66 (s, 3H, 12(1)-CH

3

); 3.61 (m, 2H, 8(1)-CH

2

); 3.50 (s, 3H, 17(4)-CH

3

); 3.37 (s, 3H, 2(1)-CH

3

); 3.31 (s, 2H, 13(4)-CH

2

); 3.16 (s, 3H, 7(1)-CH

3


2

); 2.36 (m, 2H, 17(2)-CH

2

); 1.82 (d, 3H,

J

= 7.3 Hz, 18(1)-CH3); 1.59 (t, 3H,

J

= 7.5 Hz, 8(2)-CH3); 0.32 (br s, 1H, I-NH); –1.74 (br s, 1H, III-NH)

–4.68 (s, 1B); –2.42 (d, 1B,

J

= 149.6 Hz); –9.09 (d, 3B,

J

= 150.8 Hz); –14.29 (d, 5B,

J

= 140.8 Hz)

XI

9.52 (s, 1H, 10-H); 9.38 (s, 1H, 5-H); 8.57 (s, 1H, 20-H); 7.97 (dd, 1H,

J

= 17.8 and 11.3 Hz, 3(1)-H); 6.27 (d, 1H,

J

= 17.8 Hz, 3(2)-trans); 6.23 (s, 1H, 13(2)-H); 6.16 (d, 1H,

J

= 18.2 Hz, 3(2)-cis); 4.48 (m, 1H, 18-H); 4.31 (m, 1H, 17-H); 3.68 (s, 3H, 12(1)-CH

3

); 3.66 (s, 3H, 17(4)-CH

3

); 3.51 (m, 2H,

J

= 8.2 Hz, 8(1)-CH

2

); 3.40 (s, 3H, 2(1)-CH

3

); 3.22 (s, 3H, 7(1)-CH

3

); 3.21 (br s, 2H, 13(4)-CH

2


2

); 2.14 (m, 2H, 17(2)-CH

2

); 1.82 (d, 3H,

J

= 7.3 Hz, 18(1)-CH

3

); 1.69 (t, 3H,

J

= 7.6 Hz, 8(2)-CH

3


–2.60 (s, 1B); –6.61 (d, 2B,

J

= 160.3 Hz); –10.22(d, 1B,

J

= 150.2 Hz);–13.87 (d, 5B,

J = 161.5 Hz); –17.50 (d, 1B, J = 182.2 Hz)

XII 9.48 (s, 1H, 10-H); 9.35 (s, 1H, 5-H); 8.57 (s, 1H, 20-H); 7.94 (dd, 1H, J = 17.6 and 11.4 Hz, 3(1)-H); 6.27 (d, 1H, J = 17.8 Hz, 3(2)-trans); 6.21 (s, 1H, 13(2)-H); 6.18 (d, 1H,J = 11.6 Hz, 3(2)-cis); 4.44 (m, 1H, 17-H); 4.35 (m, 1H, 18-H); 4.21 (m, 2H, 17(4)-CH2); 3.67 (s, 3H, 12(1)-CH3); 3.65 (m, 2H, 8(1)-CH2); 3.41 (s, 3H, 2(1)-CH3); 3.20 (s, 3H, 7(1)-CH3); 2.98 (br s, 2H, 13(4)-CH2); 2.43 (m, 4H, 17(1)-CH3, 17(2)-CH2);2.17 (br s, 2H, carborane CH); 1.82 (d, 3H, J = 7.2 Hz, 18(1)-CH3); 1.67 (t, 3H,J = 7.5 Hz, 8(2)-CH3); 0.52 (br s, 1H, I-NH); –1.67 (br s, 1H, III-NH)

–2.1 (d, 2B, J = 154.0 Hz); –4.91 (d, 2B, J = 146.0 Hz); –9.21 (d, 4B, J = 150.0 Hz); –11.81 (s, 4B); –13.18 (s, 8B)

XIII 9.52 (s, 1H, 10-H); 9.38 (s, 1H, 5-H); 8.57 (s, 1H, 20-H); 7.97 (dd, 1H, J = 17.8 and 11.6 Hz, 3(1)-H); 6.30 (d, 1H, J = 17.9 Hz, 3(2)-trans); 6.22 (s, 1H, 13(2)-H); 6.19 (d, 1H,J = 1.3 Hz, 3(2)-cis); 4.35 (m, 2H, 17-H, 18-H); 4.26 (m, 4H, 17(4)-CH2, 17(5)-CH2); 3.68, (s, 3H, 12(1)-CH3); 3.64 (m, 2H, 8(1)-CH2); 3.40 (s, 3H, 2(1)-CH3); 3.23 (s, 3H, 7(1)-CH3); 2.51 (m, 4H, 13(4)-CH2, 13(5)-CH2); 2.38 (m, 4H, 17(1)-CH3, 17(2)-CH2); 2.16 (br s, 2H, carborane CH); 1.82 (d, 3H, J = 7.2 Hz, 18(1)-CH3); 1.28 (c, 3H, 8(2)-CH3); 0.58 (br s, 1H, I-NH); –1.61 (br s, 1H, III-NH)

–2.28 (d, 2B, J = 143.7 Hz); –5.44 (d, 2B, J = 125.9 Hz); –9.52 (d, 4B, J = 153.1 Hz); –12.44 (s, 12B)

XIV 9.48 (s, 1H, 10-H); 9.32 (s, 1H, 5-H); 8.57 (s, 1H, 20-H); 7.94 (dd, 1H, J = 17.8 and 11.4 Hz, 3(1)-H); 6.27 (dd 1H, J = 17.8 and 1.2 Hz, 3(2)-trans); 6.21 (s 1H, 13(2)-H); 6.12 (dd 1H, J = 11.5 and 1.2 Hz, 3(2)-cis); 4.45 (m, 1H, 17-H); 4.27 (m, 2H, 18-H); 4.00 (m, 2H, 17(4)-CH2); 3.67 (s, 3H, 12(1)-CH3); 3.62 (m, 2H, 8(1)-CH2); 3.38 (s, 3H, 2(1)-CH3); 3.33 (br s, 2H, 13(4)-CH2); 3.18 (s, 3H, 7(1)-CH3); 2.56 (m, 4H, 17(1)-CH3, 17(2)-CH2); 2.42 (br s, 4H, carborane CH); 1.82 (d, 3H, J = 7.3 Hz, 18(1)-CH3); 1.66 (t, 3H, 8(2)-CH3, J = 7.5 Hz); 0.33 (br s, 1H, I-NH); –1.78 (br s, 1H, III-NH)

6.84 (s, 2B); 4.48 (s, 2B);–2.51 (d, 2B, J = 148.4 Hz); –9.21 (d, 4B, J = 150.2 Hz); –14.11 (d, 10B, J = 150.8 Hz)

296

DOKLADY CHEMISTRY Vol. 423 Part 1 2008

OL’SHEVSKAYA et al.

tumors also leads to the release of singlet oxygen andfree radicals, which damage not only cells but also ves-sels, which increases its therapeutic efficiency.

At present, a number of porphyrin- and chlorin-con-taining compounds are used in medical practice forPDT. They include Photogem®, Photofrin®, Foscan®,and Talaporfin® [1]. However, the number of problems(the low quantum yield of singlet oxygen, skin sensitiv-ity to light, hydrophobicity, sophisticated synthesis,high cost) related to the clinical use of a pharmaceuticalis stimulating the development of new methodologiesallowing the modification of photosensitizer properties.In particular, boronated porphyrins and chlorins weresuggested recently [4] for use as dual-action medicinesfor PDT and BNCT. We showed previously for PDT invivo [5, 6] that the introduction of a boron polyhedroninto a porphyrin or chlorin macrocycle improved theantitumor properties of these compounds as comparedwith analogues containing no boron.

In this paper, we report the results of the synthesis ofcarborane analogues of methylpheophorbide ‡ (I) andpheophorbide ‡ (II), which are new key compounds forthe synthesis of efficient antitumor pharmaceuticals forPDT and BNCT. The synthesis was carried out using aclassical reaction of organic chemistry, transesterifica-tion, which makes it possible to obtain carboxylic estersunder mild conditions in high yields [7].

Methylpheophorbide I was obtained from spirulinaaccording to [8]. This compound involves two reactivecenters capable of undergoing the transesterificationreaction: methoxycarbonyl groups at the 13(2)- and17(3)-positions of the chlorin macrocycle. The transes-terification of these ester groups with carborane alco-hols enables the preparation of mono- and dicarboranederivatives of methylpheophorbide ‡. The carboranealcohols used were 1-hydroxymethyl-Ó-carborane(III), 1-hydroxyethyl-Ó-carborane (IV), 9-hydroxy-methyl-Ó-carborane (V), 9-hydroxymethyl-m-carbo-rane (VI), and cesium 1-hydroxymethyl-closo-mono-carbadodecaborate (VII) [9–11]. New compounds(VIII–XI) were obtained by the transesterification ofmethylpheophorbide a I with alcohols III–VI in tolu-ene on refluxing for 3–10 h in the presence of0.05 equiv of crystalline iodine [12] or 2 equiv2-chloro-1-methylpyridinium iodide (CMPI) and4 equiv 4-(N,N-dimethylamino)pyridine (DMAP)[13]. The transesterification in the presence of iodine asa catalyst proceeds slowly to give the final products ina yield not higher than 50%. In the second case, thereactions proceed over 3–4 h to give up to 80% yieldand selectively at the methoxycarbonyl groups in the13(2)-position of the chlorin macrocycle to give 13(2)-substituted carborane esters VIII–XI.

Table 2. (Contd.)

Com-pound

1H (CDCl3, δ, ppm) 11B NMR (CDCl3, δ, ppm)

XV 9.52 (s, 1H, 10-H); 9.37 (s, 1H, 5-H); 8.57 (s, 1H, 20-H); 7.98 (dd, 1H, 3(1)-H,J = 12.3 and 16.5 Hz); 6.29 (s, 1H, 13(2)-H); 6.27 (dd, 1H, 3(2)-H-trans, J = 17.7 and 2.3 Hz); 6.16 (dd, 1H, 3(2)-H-cis, J = 11.2 and 1.7 Hz); 4.40 (m, 2H, 17-H, 18-H); 4.22 (m, 2H, 17(4)-CH2); 3.83 (m, 2H, 8(1)-CH2); 3.40 (s, 3H, 2(1)-CH3); 3.22 (s, 3H, 7(1)-CH3); 3.21 (br s, 2H, 13(4)-CH2); 2.77 (m, 4H, 17(1)-CH2, 17(2)-CH2); 2.44 (br s, 4H, carborane CH); 1.81 (d, 3H, 18(1)-CH3, J = 4.3 Hz);1.47 (t, 3H, 8(2)-CH3, J = 7.0 Hz); 0.36 (br s, 1H, I-NH); –1.75 (br s, 1H, III-NH)

–2.52 (s, 2B); –6.52 (d, 4B, J = 162 Hz); – 10.20 (d, 2B, J = 150 Hz); –13.29 (d, 4B, J = 158 Hz); –13.75 (d, 6B, J = 164 Hz); –17.35 (d, 2B, J = 182 Hz)

XVI 9.50 (s, 1H, 10-H); 9.38 (s, 1H, 5-H); 8.59 (s, 1H, 20-H); 7.95 (dd, 1H, 3(1)-H,J = 12.2 and 16.4 Hz); 6.25 (s, 1H, 13(2)-H); 6.21 (dd, 1H, 3(2)-H-trans, J = 17.5 and 2.4 Hz); 6.13 (dd, 1H, 3(2)-H-cis, J = 11.1 and 1.9 Hz); 4.43 (m, 2H, 17-H, 18-H); 4.23 (m, 2H, 17(4)-CH2); 3.88 (m, 2H, 8(1)-CH2); 3.45 (s, 3H, 2(1)-CH3); 3.26 (s, 3H, 7(1)-CH3); 3.19 (br s, 2H, 13(4)-CH2); 2.90–2.73 (m, 4H, 17(1)-CH2, 17(2)-CH2); 1.84 (d, 3H, 18(1)-CH3, J = 4.5 Hz); 1.44 (t, 3H, 8(2)-CH3, J = 7.4 Hz); 0.27 (br s, 1H, I-NH); –1.72 (br s, 1H, III-NH)

–12.35 (d, 12B, J = 136 Hz); –11.87 (d, 10B, J = 102 Hz)

Notes:VIII, 13(2)-[(o-carboran-1-yl)methoxycarbonyl]pheophorbide a methyl ester;IX, 13(2)-[(o-carboran-1-yl)ethoxycarbonyl]pheophorbide a methyl ester;X, 13(2)-[(o-carboran-9-yl)methoxycarbonyl]pheophorbide a methyl ester;XI, 13(2)-[(m-carboran-9-yl)methoxycarbonyl]pheophorbide a methyl ester;XII, 13(2),17(3)-[di(o-carboran-1-yl)methoxycarbonyl]pheophorbide a;XIII, 13(2),17(3)-[di(o-carboran-1-yl)ethoxycarbonyl]pheophorbide a;XIV, 13(2),17(3)-[di(o-carboran-9-yl)methoxycarbonyl]pheophorbide a;XV, 13(2),17(3)-[di(m-carboran-9-yl)methoxycarbonyl]pheophorbide a;XVI, 13(2),17(3)-[di(closo-monocarbadodecaboran-1-yl)methoxycarbonyl]pheophorbide a.1H and 11B NMR spectra were recorded on a Bruker Avance-400 spectrometer.


SYNTHESIS OF BORONATED DERIVATIVES OF PHEOPHORBIDE a 297

Scheme 1.

We also developed a method for the introduction oftwo carborane polyhedra into the methylpheophorbidemolecule I via the transesterification of 13(2)- and17(3)-methoxycarbonyl derivatives with the use of thedistannoxane triflate-containing complex[Bu2Sn(OH)(OTf)]2 [14]. The heating of meth-ylpheophorbide I with carborane alcohols III–VII intoluene under reflux in the presence of 1 equiv of thiscomplex for 10–15 h affords compounds XII–XVI,containing two boron polyhedra, in 65–80% yield.Using pheophorbide II as an example [15], we showedthe possibility of using [Bu2Sn(OH)(OTf)]2 in a single-step transesterification of the ester group at the 13(2)-position and the esterification of the carboxy group atthe 17(3)-position, which makes it possible to introduce

two carborane polyhedra into natural chlorin. Therefluxing of pheophorbide II in toluene with alcoholsIII–VII in the presence of [Bu2Sn(OH)(OTf)]2 led tocarborane esters XII–XVI in 60–75% yields.

All carboranylchlorins were isolated by columnchromatography as dark green crystals soluble in chlo-roform, methylene chloride, pyridine, acetone, and ace-tonitrile.

The structure of compounds VIII–XVI was con-firmed by 1ç and 11B NMR spectra, mass spectra, andelectron and infrared spectra (Tables 1, 2).

Thus, we developed an efficient one-step syntheticapproach allowing the introduction of carborane poly-hedra into the pheophorbide a macrocycle, which

VIII–XI

ROH (III)–(VI),

I2 or CMPI/ DMAP

ROH (III)–(VII),

[Bu2Sn(OH)(OTf)]2

XII–XVI

II

VIII, XII IX, XIII

X, XIV XI, XV

I

ROH (III)–(VII), [Bu2Sn(OH)(OTf)]2

R =

R = R =

R =

R =⊕

�

Cs

XVI

N

HNN

NH

OO O

RO O

Me

N

HNN

NH

OO O

MeO O

Me

N

HNN

NH

OO O

RO O

R

N

HNN

NH

OO O

MeO OH

298


OL’SHEVSKAYA et al.

opens opportunities for the search for new promisingmedicines for PDT and BNCT.

ACKNOWLEDGMENTS

This study was supported by the Russian Foundationfor Basic Research (project no. 08–03–99084-r_ofi).

REFERENCES1. Mody, T.D., J. Porphyrins Phthalocyanines, 2000,

vol. 4, pp. 362–367.2. Soloway, A.H., Tjarks, W., Barnum, B.A., et al., Chem.

Rev., 1998, vol. 98, pp. 1515–1562.3. Luo, Y., Chang, C.K.., and Kessel, D., Photochem. Pho-

tobiol., 1996, vol. 63, pp. 528–534.4. Renner, M.W., Miura, M., Easson, M.W., et al., Anti-

Cancer Agents Med. Chem., 2006, vol. 6, pp. 145–157.5. Ol’shevskaya, V.A., Nikitina, R.G., Zaitsev, A.V., et al.,

Org. Biomol. Chem,. 2006, vol. 4, pp. 3815–3821.

6. Olshevskaya, V.A., Zaitsev, A.V., Savchenko, A.N.,et al., Bull. Korean Chem. Soc., 2007, vol. 28, pp. 1910–1916.

7. Otera, J., Chem. Rev., 1993, vol. 93, pp. 1449–1470.8. Belykh, D.V., Karmanova, L.P., Spirikhin, L.V., et al.,

Mendeleev. Commun., 2002, pp. 77–78.9. Zakharkin, L.I., Brattsev, V.A., and Stanko, V.I., Zh. Org.

Khim., 1966, vol. 36, pp. 886–892.10. Zakharkin, L.I., Ol’shevskaya, V.A., and Boiko, N.B.,

Izv. Akad. Nauk, Ser. Khim., 1996, no. 12, pp. 719–722.11. Zakharkin, L.I., Ol’shevskaya, V.A., Petrovskii, P.V.,

et al., Mendeleev Commun., 2000, pp. 71–72.12. Ramalinga, K., Vijayalakshmi, P.., and Kaimal, T.N.B.,

Tetrahedron Lett., 2002, vol. 43, pp. 879–882.13. Shinoda, S.. and Osuka, A., Tetrahedron Lett., 1996,

vol. 37, pp. 4945–4948.14. Lee, H., Bae, J.Y., Kwon, O-S., et al., J. Organomet.

Chem., 2004, vol. 689, pp. 1816–1820.15. Brandis, A.S., Kozyrev, A.N.., and Mironov, A.F., Tetra-

hedron, 1992, vol. 48, pp. 6485–6494.

synthesis of boronated derivatives of pheophorbide a

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