2,5-Dihydroxybenzyl and (1,4-dihydroxy-2-naphthyl)methyl, novel reductively armed photocages for the hydroxyl moiety

Article abstract of DOI:10.1021/jo701426j

(Chemical Equation Presented) Irradiation of alcohols, phenols, and carboxylic acids "caged" with the 2,5-dihydroxybenzyl group or its naphthalene analogue results in the efficient release of the substrate. The initial byproduct of the photoreaction, 4-hydroxyquinone-2-methide, undergoes rapid tautomerization into methyl p-quinone. The UV spectrum of the latter is different from that of the caging chromophore, thus permitting selective irradiation of the starting material in the presence of photochemical products. These photoremovable protecting groups can be armed in situ by the reduction of photochemically inert p-quinone precursors.

Full text of DOI:10.1021/jo701426j

2,5-Dihydroxybenzyl and (1,4-Dihydroxy-2-naphthyl)methyl, Novel
Reductively Armed Photocages for the Hydroxyl Moiety
Alexey P. Kostikov and Vladimir V. Popik*
Department of Chemistry, UniVersity of Georgia, Athens, Georgia 30602
Vpopik@chem.uga.edu
ReceiVed July 1, 2007
Irradiation of alcohols, phenols, and carboxylic acids “caged” with the 2,5-dihydroxybenzyl group or its
naphthalene analogue results in the efficient release of the substrate. The initial byproduct of the
photoreaction, 4-hydroxyquinone-2-methide, undergoes rapid tautomerization into methyl p-quinone. The
UV spectrum of the latter is different from that of the caging chromophore, thus permitting selective
irradiation of the starting material in the presence of photochemical products. These photoremovable
protecting groups can be armed in situ by the reduction of photochemically inert p-quinone precursors.
Introduction
Byproducts of the uncaging reaction should ideally be transpar-
ent at the wavelength of irradiation and possess low reactivity.
Photolabile protecting groups (PPG), known as “cages” in
biochemistry, allow for the spatial and temporal control of
substrate release, as well as “reagentless” deprotection.1-3 PPGs
have found numerous applications in biochemistry,3 organic
synthesis,1,2 fabrication of high-density probe arrays (aka
biochips),4 and time-resolved X-ray crystallography.5 To exploit
benefits of photochemical deprotection, the caging group should
comply with the following requirements: high quantum and
chemical yields, as well as a fast rate of substrate release;
substantial absorbance above 300 nm; and good dark stability.
Among common functional groups, alcohols are one of the
most difficult functionalities to cage. Several examples of
successful release of alcohols and carbohydrates caged with
o-nitrobenzyl-based PPGs have been reported.2,6 However,
substrate release can take minutes after irradiation since this
reaction proceeds via several slow dark steps.7 Other common
PPGs, such as 3′,5′-dimethoxybenzoin,8 p-hydroxyphenacyl,9
and a family of cages utilizing photochemical heterolysis of
the C-O bond,10 allow for the rapid release of a substrate but
work well only with good leaving groups and are rarely suitable
for the direct caging of alcohols.11 The quantum and chemical
(1) Greene, T. W.; Wuts, P. G. M. ProtectiVe Groups in Organic
Synthesis; Wiley: New York, 1991.
(2) (a) Pelliccioli, A. P.; Wirz, J. Photochem. Photobiol Sci. 2002, 1,
441. (b) Bochet, C.G. J. Chem. Soc., Perkin Trans. 1 2002, 125.
(3) (a) Morrison, H., Ed. Biological Applications of Photochemical
Switches; Wiley: New York, 1993. (b) Goeldner, M., Givens, R., Eds.
Dynamic Studies in Biology; Wiley: Weinheim, Germany, 2005. (c) Mayer,
G.; Heckel, A. Angew. Chem., Int. Ed. 2006, 45, 4900.
(4) (a) Fodor, S. P. A.; Read, J. L.; Pirrung, M. C.; Stryer, L.; Lu, A. T.;
Solas, D. Science 1991, 251, 767. (b) Heller, M. J. Annu. ReV. Biomed.
Eng. 2003, 4, 129. (c) Gao, X.; LeProust, E.; Zhang, H.; Srivannavit, O.;
Gulari, E.; Yu, P.; Nishiguchi, C.; Xiang, Q.; Xiaochuan, Z. Nucleic Acids
Res. 2001, 29, 4744. (d) Lipshutz, R. J.; Fodor, S. P. A.; Gingeras, T. R.;
Lockhart, D. J. Nat. Genet. 1999, 21, 20. (e) Pirrung, M. C.; Fallon, L.;
McGall, G. J. J. Org. Chem. 1998, 63, 241.
(6) (a) Specht, A.; Goeldner, M. Angew. Chem., Int. Ed. 2004, 43, 2008.
(b) Corrie, J. E. T. J. Chem. Soc., Perkin Trans. 1 1993, 2161. (c) Watanabe,
S.; Sueyoshi, T.; Ichihara, M.; Uehara, C.; Iwamura, M. Org. Lett. 2001,
3, 255.
(7) (a) Corrie, J. E. T.; Barth, A.; Munasinghe, V. R. N.; Trentham, D.
R.; Hutter, M. C. J. Am. Chem. Soc. 2003, 125, 8546. (b) Il’ichev, Y. V.;
Schworer, M. A.; Wirz, J. J. Am. Chem. Soc. 2004, 126, 4581.
(8) (a) Sheehan, J. C.; Wilson, R. M.; Oxford, A. W. J. Am. Chem. Soc.
1971, 93, 7222. (b) Givens, R. S.; Athey, P. S.; Matuszewski, B.; Kueper,
L. W., III; Xue, J.-y.; Fister, T. J. Am. Chem. Soc. 1993, 115, 6001.
(9) (a) Givens, R. S.; Park, C.-H. Tetrahedron Lett. 1996, 37, 6259. (b)
Givens, R. S.; Weber, J. F. W.; Conrad, P. G. II; Orosz, G.; Donahue, S.
L.; Thayer, S. A. J. Am. Chem. Soc. 2000, 122, 2687.
(5) (a) Srajer, V.; Teng, T.-Y.; Ursby, T.; Pradervand, C.; Ren, Z.; Adachi,
S.-I.; Schildkamp, W.; Bourgeois, D.; Wulff, M.; Moffat, K. Science 1996,
274, 1726. (b) Schlichting, I.; Almo, S. C.; Rapp, G.; Wilson, K.; Petratos,
K.; Lentfer, A.; Wittinghofer, A.; Kabsch, W.; Pai, E. F.; Petsko, G. A.;
Goody, R. S. Nature 1990, 345, 309.
(10) (a) Chamberlin, J. W. J. Org. Chem. 1966, 31, 1658. (b) Scho¨nleber,
R. O.; Bendig, J.; Hagen, V.; Giese, B. Bioorg. Med. Chem. 2002, 10, 97.
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10.1021/jo701426j CCC: $37.00 © 2007 American Chemical Society
Published on Web 10/25/2007
9190
J. Org. Chem. 2007, 72, 9190-9194

NoVel ReductiVely Armed Photocages
SCHEME 1
yield of alcohol photorelease can be improved substantially by
the introduction of a carbonate linker between the substrate and
the cage.12 In this case, however, the relatively slow dark
decarboxylation of a monocarbonate becomes the rate-determin-
ing step of the alcohol release.13 Photoremovable protecting
groups based on photoinduced electron transfer often allow for
the efficient deprotection of alcohols but require the addition
of a sensitizer and/or an electron donor.14
SCHEME 2
Our group is interested in developing new PPGs based on
the photochemistry of o-hydroxybenzyl ethers and esters.
o-Hydroxybenzyl alcohol and its derivatives lose water upon
irradiation, generating reactive o-quinone methides.15 The
formation of the o-quinone methide is usually complete within
the nanosecond laser pulse. It apparently proceeds via the
excited-state proton transfer, accompanied by a concerted C-O
bond cleavage (Scheme 1). Recently, we have shown that ethers
and esters of (3-hydroxymethyl)naphthalen-2-ol (1) efficiently
release the corresponding hydroxy compounds upon irradiation
(Scheme 1).16 (3-Hydroxymethyl)naphthalen-2-ol was chosen
over o-hydroxybenzyl alcohol because it allows for the use of
longer irradiation wavelengths for deprotection.
SCHEME 3 a
In aqueous solvents, intermediate o-quinone methide 2 rapidly
adds water to form the parent diol 1a. The transient 2 has a
microsecond life time in wholly aqueous solution.15 This cage
is well-suited for the time-resolved release of hydroxyl com-
pounds in aqueous media. Under steady-state irradiation,
however, accumulation of (3-hydroxymethyl)naphthalen-2-ol
(1a), which has the same chromophore as the caged compound,
causes the filtering effect and reduces yields of deprotection.
To alleviate this problem, we have designed a new PPG, 2,5-
dihydroxybenzyl (3, Scheme 2). The 4-hydroxy-1-quinone-2-
methide intermediate 5, formed upon deprotection of the
substrate, undergoes rapid tautomerization to stable 2-methyl-
1,4-benzoquinone (6). The UV spectrum of the latter is signi-
ficantly different from that of 3, allowing for selective irradiation
of the caged compound even at higher substrate concentrations
(Figure 1). The photochemical properties of the naphthalene
analogue of 3 have been also explored (4, Scheme 2).
a Reagents and conditions: (a) R ) PhCH2CH2: (i) HBr (aq) 91%; (ii)
PhCH2CH2OH, NaH, THF 85%; R ) PhCO: PhCOCl, CH2Cl2, pyridine
81%; R ) t-BuCO: t-BuCOCl, CH2Cl2, pyridine 84%; (b) CAN, CH3CN,
71-87%; (c) Na2S2O4, H2O/CHCl3 90-99%.
Results and Discussion
2,5-Dihydroxybenzyl-caged 2-phenylethanol (3a), as well as
benzoic (3c) and pivalic (3d) acids, was prepared by the
FIGURE 1. UV spectra of ca. 5 × 10-5 M methanol solutions of
caged 2-phenylethanol 3a (solid line), methylbenzoquinone (6, dashed
line), and p-chlorophenol (dotted line).
(12) (a) Loudwig, S.; Maurice, G. Tetrahedron Lett. 2001, 45, 7957. (b)
Suzuki, A. Z.; Watanabe, T.; Kawamoto, M.; Nishiyama, K.; Yamashita,
H.; Ishii, M.; Iwamura, M.; Furuta, T. Org. Lett. 2003, 5, 4867. (c) Pirrung,
M. C.; Bradley, J.-C. J. Org. Chem. 1995, 60, 1116.
(13) (a) Papageorgiou, G.; Barth, A.; Corrie, J. E. T. Photochem.
Photobiol. Sci. 2005, 4, 216. (b) Literak, J.; Wirz, J.; Klan, P. Photochem.
Photobiol. Sci. 2005, 4, 43.
(14) (a) Banerjee, A.; Lee, K.; Falvey, D. E. Tetrahedron 1999, 55,
12699. (b) Jones, P. B.; Pollastri, M. P.; Porter, N. A. J. Org. Chem. 1996,
61, 9455. (c) Falvey, D. E.; Sundararajan, C. Photochem. Photobiol. Sci.
2004, 3, 831.
reduction of corresponding quinones 7a,c,d with sodium
dithionite in a biphasic chloroform-water system (Scheme 3).
Direct acylation of the starting 2,5-dimethoxybenzyl alcohol
(8), which was prepared from commercially available 2,5-
dimethoxybenzaldehyde,17 afforded esters 9c,d in good yield.
For the synthesis of ether 9a, alcohol 8 was first converted into
(15) (a) Diao, L.; Yang, C.; Wan, P. J. Am. Chem. Soc. 1995, 117, 5369.
(b) Nakatani, K.; Higashida, N.; Saito, I. Tetrahedron Lett. 1997, 38, 5005.
(c) Fischer, M.; Shi, Y.; Zhao, B.-p.; Snieckus, V.; Wan, P. Can. J. Chem.
1999, 77, 868. (d) Chiang, Y.; Kresge, A. J.; Zhu, Y. J. Am. Chem. Soc.
2002, 124, 717.
(16) Kulikov, A. V. Dissertation, Bowling Green State University,
Bowling Green, OH, 2006.
(17) Kumar, S. K.; Amador, M.; Hidalgo, M.; Bhat, S. V.; Khan, S. R.
Bioorg. Med. Chem. 2005, 13, 2873.
J. Org. Chem, Vol. 72, No. 24, 2007 9191

Kostikov and Popik
TABLE 1. Photochemical Release of Substrates from Caged
2,5-dimethoxybenzyl bromide, which was then reacted with
sodium 2-phenylethoxide in THF. 2,5-Dimethoxybenzyl deriva-
tives 9a,c,d were converted into the corresponding quinones
7a,c,d by oxidation with cerium ammonium nitrate (CAN).18
p-Chlorophenol was caged using a different approach: bis-
TBDMS-protected 2,5-dihydroxybenzyl alcohol (10) was pre-
pared by TBDMS protection and subsequent sodium borohy-
dride reduction of 2,5-dihydroxybenzaldehyde (Scheme 4).
Alcohol 10 was coupled with p-chlorophenol under modified
Mitsunobu conditions.19 TBAF-promoted deprotection of the
resulting hydroquinone (11) produced 2-(4-chlorophenoxym-
ethyl)-1,4-benzohydroquinone (3b) in a good yield.
Compounds 3a-d and 4a,b
λirradiation
Φ
yield of the
(%) substrate (%)
yield of quinone
6 or 6N (%)
solvent
3a MeOH
MeCN/H2Oa
3b MeOH
MeOH/H2Oa
3c MeOH
MeCN/H2Oa
3d H2O
(nm)
300
300
300
300
300
300
300
300
350
300
350
350
19
30
31
50
6
11
31
31
29
20
25
7
79
80
28
traces
14
26
21
traces
traces
43
49
58 (84)b
59
55
quantitative
4a MeOH
99
94
87
70
85
MeOH
35
MeCN/H2Oa
traces
traces
traces
MeCN/H2Oa
4b MeOH
SCHEME 4 a
a 1/1 ratio. b 40% conversion.
benzoic acid. We believe that relatively low quantum and
chemical yields of substrate release from 3c can be explained
by energy transfer from the caging chromophore to the benzoate
moiety. Pivalic acid, for which such process is not viable, was
deprotected quantitatively. Yield of p-chlorophenol at complete
consumption of 3b was in the range of 50-60%, and HPLC
analysis of the reaction mixture indicated the presence of
numerous minor byproducts. This can be explained by secondary
photochemical decomposition of the phenol since its longer
wavelength band (λmax ) 290 nm, dotted line in Figure 1) over-
laps with emission of the source. In fact, the yield of p-chloro-
phenol at 40% conversion of 4b was above 80% (Table 1).
In an attempt to shift the absorbance of the caging chro-
mophore to longer wavelengths, we have explored photochemi-
cal properties of the naphthalene analogue of 2,5-dihydroxy-
benzyl cage. Preparation of (1,4-dihydroxy-2-naphthyl)methyl-
caged 2-phenylethanol (4a) and p-chlorophenol (4b) was similar
to the synthesis of 3a (Scheme 5).
a Reagents and conditions: (a) (i) TBDMSCl, imidazole, DMF; (ii)
NaBH4, MeOH 79%; (b) p-ClC6H4OH, ADDP, n-Bu3P, benzene 98%; (c)
TBAF, THF 88%.
2,5-Dihydroxybenzyl-caged compounds 3a-d are stable in
the dark in neat form, as well as in acetonitrile-water or
methanol solutions. UV spectra of these compounds exhibit a
characteristic band of the 2,5-dihydroxybenzyl group at λmax
)
297 nm. The expected product of the uncaging reaction, methyl
p-benzoquinone (6), on other hand, has little absorption at this
wavelength (Figure 1).
Irradiation of ca. 0.001 M solutions of compounds 3a-d in
various solvents using 300 nm light resulted in the rapid
bleaching of 297 nm band and the formation of a new band at
246 nm, which corresponds to methyl p-benzoquinone (6, Figure
2). The release of substrates was monitored by HPLC or GC,
while the quantum yields of uncaging were calculated using
chemical actinometry20 (Table 1).
SCHEME 5 a
a Reagents and conditions: (a) (i) CBr4, PPh3, CH3CN; (ii) R )
PhCH2CH2: BuLi, 2-phenylethanol, THF 63%; or R ) p-ClC6H4: Na2CO3,
p-chlorophenol, THF 92%; (b) CAN, CH3CN, 87-92%; (c) Na2S2O4, H2O/
CHCl3 90-92%.
1,4-Dimethoxy-2-naphthylmethanol (12), which was prepared
from 1,4-dihydroxy-2-naphthoic acid,21 was treated with carbon
tetrabromide in the presence of triphenylphosphine to give
2-bromomethyl-1,4-dimethoxynaphthalene. Reaction of the latter
with 2-phenylethoxide or p-chlorophenolate in THF produced
ethers 13a or 13b, respectively. Quinones 14a,b were obtained
by oxidative deprotection of the methoxy groups in 13a,b and
then reduced to target hydroquinones 4a,b with sodium dithion-
ite (Scheme 5).
The absorbance of the (1,4-dihydroxy-2-naphthyl)methyl
chromophore extends up to 400 nm, allowing for the use of
longer wavelengths for uncaging than in the case of the 2,5-
dihydroxybenzyl chromophore (Figure 3). Irradiation of 4a at
either 300 or 350 nm results in bleaching of the starting material
FIGURE 2. Photolysis of 5 × 10-5 M methanol solutions of 3a.
Photodeprotection of 2,5-dihydroxybenzyl-caged substrates
is quite efficient (Φ300 nm ) 0.2-0.5), with the exception of
(18) Jacob, P., III; Callery, P. S.; Shulgin, A. T.; Castagnoli, N. J. Org.
Chem. 1976, 41, 3627.
(19) Falck, J. R.; Yu, J.; Cho, H.-S. Tetrahedron Lett. 1994, 35, 5997.
(20) Murov, S. L.; Carmichael, I.; Hug, G. L. In Handbook of
Photochemistry; Marcel Dekker: New York, 1993; p 299.
(21) Flader, C.; Liu, J.; Borch, R. F. J. Med. Chem. 2000, 43, 3157.
9192 J. Org. Chem., Vol. 72, No. 24, 2007

NoVel ReductiVely Armed Photocages
SCHEME 6
In a sharp contrast with a previous experiment, the reaction
mixture did not contain compounds 6 or 15 after 1 h of steady-
state irradiation of a methanol solution of 3a with 450 W
medium-pressure Hg lamp. 2,5-Dihydroxybenzaldehyde (16)
and methyl-p-hydroquinone (17) were only isolated byproducts.
These observations suggest that quinone 6 oxidizes methyl
benzyl ether 15 to aldehyde 16 in a photochemically driven
redox reaction. Quinone 6 is observed by HPLC in low
conversion photolysis of 3a in aqueous acetonitrile. However,
only 16 and 17 were isolated after complete uncaging of the
substrate. The faster consumption of benzoquinone (6) in
aqueous solutions is apparently due to the fact that 2,5-
dihydroxybenzyl alcohol (3, R ) H), which is expected to be
produced in the presence of water, undergoes much faster
oxidation than methyl ether 15. In fact, direct irradiation of
methanol solution of 6 and 2,5-dihydroxybenzyl alcohol at 300
nm results in the formation of 16 and 17.
FIGURE 3. UV spectra of 5 × 10-5 M methanol solutions of 4a
recorded after 0, 1, 3, 5, 7, 10, and 15 min of irradiation.
(Figure 3) and efficient deprotection of the substrate (Table 1).
In aqueous acetonitrile, release of 2-phenylethanol is almost
quantitative, while yields are slightly lower in methanol.
Photolysis of (1,4-dihydroxy-2-naphthyl)methyl-caged p-chlo-
rophenol 4b at 350 nm regenerated the substrate in 85% yield
at full conversion. This result supports the suggestion that poor
yield of p-chlorophenol in high conversion photolysis of 3b is
due to secondary photochemical transformations of the substrate
(Table 1).
Overall, irradiation of (1,4-dihydroxy-2-naphthyl)methyl-
caged substrates produces somewhat higher yields of substrate
release than 2,5-dihydroxybenzyl-protected hydroxy compounds
(Table 1). However, the former are less stable and undergo slow
decomposition in aqueous solutions and in the solid state under
ambient conditions. We are currently exploring analogues of
4a with various substituents on the naphthalene ring in an
attempt to enhance the stability of (1,4-dihydroxy-2-naphthyl)-
methyl-caged compounds.
Naphthoquinone precursors 14a,b, on the other hand, are
perfectly stable in solution and in the solid state. The photo-
chemical stability of quinones 7a,c,d and 14a,b is also
noteworthy. Irradiation of these compounds at 300 or 350 nm
for the period of time required for the complete consumption
of 3a,c,d and 4a,b does not result in any detectable decomposi-
tion of quinones or release of the caged substrates. Since
quinones 7a,c,d and 14a,b are quantitatively reduced to target
hydroquinones 3a,c,d and 4a,b under very mild conditions,
stable protecting groups in 7 and 14 can be “armed” in situ by
using a suitable reducing agent.
The release of hydroxy compounds from caged precursors
3a-d and 4a,b is accompanied by pronounced bleaching, but
expected 2-methyl benzoquinone (6) is formed in surprisingly
low yield (Table 1). To test whether 6 undergoes subsequent
photoconversion under steady-state irradiation, we have con-
ducted preparative photolyses of 3a under various conditions.
Irradiation of 3a in the flow photoreactor22 allowed us to achieve
complete conversion of the starting material but limit exposure
of the photoproducts. Only methyl p-quinone (6) and 2,5-
dihydroxybenzyl methyl ether 15, along with 2-phenylethanol,
were isolated from the photolysate. Ether 15 is apparently
formed by a competitive nucleophilic addition of methanol to
the transient quinone methide 5 (Scheme 6).
Conclusions
Two novel photolabile protecting groups, 2,5-dihydroxyben-
zyl and (1,4-dihydroxynaphthyl)methyl, were tested for caging
of various hydroxy groups. 2,5-Dihydroxybenzyl and (1,4-
dihydroxynaphthyl)methyl-caged aliphatic acids, phenols, and
alcohol derivatives efficiently release the substrate upon ir-
radiation at 300 or 350 nm in a good to excellent yield.
Photodeprotection is accompanied by substantial bleaching,
allowing for the use of a higher substrate concentration. Alcohols
can be directly caged with these PPGs without the necessity of
a carbonate linker. This enhances the hydrolytic stability of
caged alcohols and makes fast (τ < 1 µs) release of the
substrates possible. Quinone precursors of 2,5-dihydroxybenzyl
and (1,4-dihydroxynaphth-2-yl)methyl cages are photochemi-
cally inert but can be quantitatively converted into photoreactive
form using mild reducing agents. Our current work is focused
on the mechanism and dynamics of the photorelease and on
the tuning of photochemical properties of this novel class of
protecting groups.
Experimental Section
General Procedure for the Conversion of Dimethoxyarenes
into Quinones. 2-(Phenethyloxymethyl)-1,4-benzoquinone (7a):
An aqueous solution of cerium ammonium nitrate (2.74 g, 5 mmol)
was added to a solution of 9a (231 mg, 0.77 mmol) in acetonitrile
(25 mL) and stirred at room temperature for 30 min. The reaction
mixture was extracted with ether; the combined organic layers were
washed with brine and dried over Na2SO4, and solvents were
removed in vacuo. Chromatographic purification (hexane/ether )
4:1) gave 148 mg (0.61 mmol, 79%) of quinone 7a as a bright
(22) Hook, B. D. A.; Dohle, W.; Hirst, P. R.; Pickworth, M.; Berry, M.
B.; Booker-Milburn, K. I. J. Org. Chem. 2005, 70, 7558.
J. Org. Chem, Vol. 72, No. 24, 2007 9193

Kostikov and Popik
yellow oil; 7c yellow oil, 71%; 7d yellow oil, 73%; 14a yellow
crystals, 87%; 14b yellow crystals, 92%.
1:1) gave 128 mg (0.53 mmol, 99%) of 3a as white solid; 3c
colorless oil, 99%; 3d colorless oil, 97%; 4a air-sensitive white
solid, 90%; 4a air-sensitive white solid, 92%.
General Procedure for the Reduction of Quinones to Hyd-
roquinones. 2-Phenethyloxymethylbenzene-1,4-diol (3a): A solu-
tion of sodium dithionite (870 mg, 5 mmol) in 25 mL of water
was added to a solution of 7a (128 mg, 0.53 mmol) in 25 mL of
chloroform. The mixture was vigorously stirred until the complete
disappearance of yellow color. One hundred milliliters of 10%
aqueous ammonium chloride was added to the reaction mixture,
and the aqueous layer was extracted with ether (2 × 50 mL). The
combined organic layers were washed with 10% aqueous am-
monium chloride (2 × 50 mL) and dried over Na2SO4, and solvents
were removed in vacuo. Column chromatography (hexane/ether )
Acknowledgment. Authors thank the NSF (CHE-0449478)
and Georgia Cancer Coalition for the support of this project.
Supporting Information Available: Preparative procedures,
analytical data, and 1H and 13C NMR spectra of newly synthesized
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO701426J
9194 J. Org. Chem., Vol. 72, No. 24, 2007