A Novel PPh3 Mediated One-Pot Method for Synthesis of 3-Aryl or Alkyl 1,2-Benzisoxazoles

Article abstract of DOI:10.1021/acs.orglett.7b00563

A novel, efficient, and facile protocol has been developed for transforming 2-hydroxybenzonitriles and bromides into a range of 3-aryl or alkyl substituted 1,2-benzisoxazoles in good to excellent yields mediated by PPh₃. The electronic and steric effects of bromides on the reaction are discussed. This is the first example to construct a C-C bond and heterocycle in a Barbier-Grignard-type reaction featuring easier recovery of PPh₃ than a metallic catalyst in one step.

Full text of DOI:10.1021/acs.orglett.7b00563

Letter
pubs.acs.org/OrgLett
A Novel PPh3 Mediated One-Pot Method for Synthesis of 3‑Aryl or
Alkyl 1,2-Benzisoxazoles
GuiFang Chen,†,§ Hong Liu,†,§ ShuJia Li,† Yu Tang,*,† PeiYao Lu,‡ KaiTian Xu,†
and YuanMing Zhang*,†
†Department of Chemistry, College of Chemistry and Materials, Jinan University, Guangzhou 510632, China
‡Department of Pharmacy, College of Pharmacy, Jinan University, Guangzhou 510632, China
S
* Supporting Information
ABSTRACT: A novel, efficient, and facile protocol has been
developed for transforming 2-hydroxybenzonitriles and
bromides into a range of 3-aryl or alkyl substituted 1,2-
benzisoxazoles in good to excellent yields mediated by PPh3.
The electronic and steric effects of bromides on the reaction
are discussed. This is the first example to construct a C−C
bond and heterocycle in a Barbier−Grignard-type reaction featuring easier recovery of PPh3 than a metallic catalyst in one step.
Scheme 1. Synthetic Approaches to 1,2-Benzisoxazoles
he various pharmaceutical and therapeutic agents
1
Tcontaining a 1,2-benzisoxazole scaffold,
particularly 3-
substituted derivatives,2 show a wide spectrum of bioactivity,
such as antipsychotic,3 antitumor,4 antimicrobial,6 anticonvul-
sant,5 antibacterial,7 diuretic,8 antithrombotic,9 and acetyl-
cholinesterase inhibition10a properties. This high bioactivity
exhibited by the derivatives is reflected in Zonisamide,11 a novel
antiepileptic drug approved by the United States FDA in 2000
as an adjunctive treatment for partial seizures.11a In addition, N-
benzylpiperidine benzisoxazoles have been developed as potent
and selective inhibitors of the enzyme acetylcholinesterase
(ACHE), which may make them suitable compounds for the
palliative treatment of Alzheimer’s Disease.10b Therefore, these
relevant structures have been employed widely as carriers for
pharmacophoric moieties in the search for potential drugs in
immediate applications.12 Hence, great efforts have been made
to synthesize 1,2-benzisoxazoles, driven in part by the expected
biological activities. In general, the reported synthesis of 1,2-
benzisoxazoles could be found utilizing five distinct approaches
(Scheme 1): (1) [3 + 2]-cycloaddition of in situ generated
nitrile oxides to arynes;2,13 (2) catalyzed cyclodehydration of 2-
hydroxyaryl aldoximes and ketoximes;14 (3) catalyzed intra-
molecular nucleophilic substitution of oximes in the presence of
strong bases;15 (4) palladium-catalyzed intermolecular [4 + 1]-
annulation of N-phenoxy acetamide with aldehydes;16 (5)
intramolecular cycloaddition of SNAr products from fluorous
oxime tags or polymer-bound oximes to o-fluoro-benzoni-
triles.17 Yet, some limitations and drawbacks of these
approaches could still be found such as the requirement of
3−4 steps for most reported procedures, preparation of starting
materials or a long reaction time,2,10b formation of undesirable
byproducts,9,13a and some harsh reaction conditions such as a
strong base in the substitution of aryl halides.15a,c,17
method for the synthesis of 3-substituted 1,2-benzisoxazoles
would be highly desirable. In the process to investigate the
cross-coupling of phenolic ketones,20 we observed the
formation of 3-phenyl-1,2-benzisoxazole using 2-hydroxy-
benzonitrile to react with bromobenzene. Herein, we are
delighted to present our results about such a novel, highly
efficient, and convenient protocol for the synthesis of 3-
substituted 1,2-benzisoxazoles from 2-hydroxybenzonitriles and
bromides mediated by PPh3. To the best of our knowledge, this
is the first example to construct a C−C bond and heterocycle in
the Barbier−Grignard-type reaction in one step.
After determining the effects of time, temperature, and
amount of 2a (bromobenzene) and Mg on the reaction (see
On the other hand, the basic conditions in intramolecular
cyclization often led to Beckmann-type rearrangement18 and
deoxidation side reactions.19 Thus, the development of a new
Received: February 23, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.7b00563
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Organic Letters
Letter
Supporting Information Table S1), we attempted to reduce the
excess reactants using catalysts. Catalysts BiCl3, FeCl3, and
NiCl2 were first examined by the reaction of 2.5 equiv of 2a and
Mg, but all resulted in lower yields (Table 1, entries 1−4). A
77% (Table 2, entry 5), DPPP was not effective (Table 2, entry
4). Afterward, it was interesting to find PPh3 itself could
catalyze the reaction to give yields of 69%, 74%, and 74%
corresponding 10, 15, and 20 mol % of PPh3 (Table 2, entries
6−8), respectively. To gain an excellent yield, the reaction of 2
equiv of 2a and Mg was performed in the presence of 15 mol %
PPh3 or 15 mol % PPh3 and 5 mol % of Eu2O3, which furnished
a 92% or an 84% yield (Table 2, entry 9), respectively. The
result indicates there is no synergistic effect between Eu2O3 and
PPh3. Thus, the optimal conditions were determined to include
Eu2O3 (5 mol %) or PPh3 (15 mol %) as the catalyst, with 1a
(5 mmol) reacted with 2 equiv of 2a and Mg in 7.5 mL of THF
and 17.5 mL of toluene at 90 °C for 4 h. Under the optimized
conditions, 3 equiv of PhMgBr prepared in advance were
examined in place of 2a and Mg in the reaction, and the result
of 69% yield (Table 2, entry 10) indicates the in situ formation
of PhMgBr from 2a and Mg is more efficient.
Table 1. Effect of Metallic Catalysts on the Reaction
yield
a
a
entry
cat. (mol %)
None
(%)
entry cat. (mol %)
yield (%)
1
2
3
4
5
6
7
81
8
Cp2TiCl2 (10) 32
BiCl3 (10)
FeCl3 (10)
NiCl2 (10)
56
48
47
9
CuBr2 (10)
Nb2O5 (10)
Eu2O3 (10)
Eu2O3 (5.0)
Eu2O3 (2.5)
Eu2O3 (15)
66
91(68)
b
b
10
11
12
13
14
c
91(90) (72)
b
b
c
Nano CuO (10) 89(71)
92 (70)
b
To test the scope of this protocol, some 2-hydroxy aromatic
nitriles 1 and bromides 2 were examined under the optimal
conditions (Scheme 2). Catalyzed by PPh3, the aryl bromides
with an electron-donating group of methyl or methoxy afforded
Cu2O (10)
CuI(10)
48
64
50
c
70
a
b
c
Isolated yields based on 1a. 2 equiv of 2a and Mg. 1.5 equiv of 2a
and Mg.
a
Scheme 2. Scope of 2-Hydroxybenzonitrile and Bromides
high yield of 89% was obtained when using nano-CuO (Table
1, entry 5) as a catalyst. Thus, other copper catalysts such as
Cu2O, CuI, and CuBr2 were investigated. But the results were
disappointing (Table 1, entries 6−8). We next considered that
highly valent metal oxides would facilitate reaction. Thus,
Nb2O5 and Eu2O3 were investigated as a catalyst in the
reaction, which afforded the product in a high yield of about
91% (Table 1, entries 9 and 10). Then, we reduced the amount
of 2a and Mg to 2 equiv in the presence of nano-CuO, Nb2O5,
or Eu2O3. As a resultl, only Eu2O3 gave a high yield of 90%
(Table 1, entry 10). The yields of 92% and 50% (Table 1, entry
10 and 12) obtained corresponding to 5 and 2.5 mol % of
Eu2O3 respectively indicated 5 mol % was the optimal amount
for the reaction. When 1.5 equiv of 2a and Mg were employed,
only about 70% of the yields could be generated even when 15
mol % of Eu2O3 was used (Table 1, entries 10−11 and 13).
Then, we explored if the reaction with 1.5 equiv of 2a and
Mg could be improved using a ligand to cooperate with Eu2O3.
The reactions employing some N-containing ligands afforded
yields close to or lower than 70% (Table 2, entries 1−3)
obtained in the ligand-free case (Table 1, entries 11). Although
PPh3 mediated the reaction to give a slightly higher yield of
Table 2. Effect of Ligands on the Reaction
yield
a
ligand
(mol %)
a
entry
ligand (mol %)
(%)
entry
yield (%)
b
1
2
3
4
5
TMEDA (10)
TED (10)
71
69
55
71
77
6
PPh3 (10)
PPh3 (15)
PPh3 (20)
PPh3 (15)
PPh3 (15)
69
b
7
74
L(−)-Proline (10)
DPPP(10)
8
74
c
d
9
92 (84)
e
PPh3 (10)
10
69
a
Isolated yields based on 1 and mediated by PPh3(Eu2O3). If the
a
b
c
Isolated yields based on 1a. Without Eu2O3. Without Eu2O3, 2a,
reaction could not start within a short amount of time, a small amount
d
b
and Mg (10 mmol). Eu2O3 (5 mol %), 2a, and Mg (10 mmol).
of iodine could be added without affecting the yields. New
e
c
d
PhMgBr (15 mmol) prepared in advance.
compound. Na (5 mmol). 4 equiv of 2 and Mg.
B
DOI: 10.1021/acs.orglett.7b00563
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Organic Letters
Letter
the corresponding products in high yields from 81% to 97%
(3ab−3ae). Because of steric hindrance, ortho substituted
bromides resulted in lower yields than their para counterparts.
The weak electron-withdrawing effect of 3-methoxy, 3-fluoro,
and 4-chloro on bromobenzenes did not affect the PPh3
mediated reactions to give excellent yields (3af−3ai).
Compared with 3ae, the 95% yield of 3af indicated the 4-
methoxy even could surmount the steric hindrance of 2-
methoxy on bromobenzene to some extent. Ortho chloro-
substituted 2j caused the yield to significantly decrease to 47%
(3aj). Using 1-bromonaphthalene and 2-bromothiophene,
good yields of 86% (3ak) and 70% (3al) were obtained,
respectively. The obtained excellent yields close to 90% indicate
an electron-donating group such as 4-methoxy on bromoben-
zene exhibits a beneficial effect on the reactions (3bc, 3cc). But
the steric hindrance of methoxy on benzonitrile 1d caused the
reaction to give a low yield of 34% (3da). As in the case of a
similar situation in another Barbier−Grignard-type reaction,20
alkyl bromides were less reactive than aromatic bromides
(3am−3ao). 4 equiv of secondary alkyl bromides were needed
to provide about 60% yields (3an, 3ao).
In general, PPh3 displayed a better catalytic effect on the
reaction than Eu2O3. Compared with Eu2O3, PPh3 would be
easier to recover. It was interesting to find that, in the reaction
of o-methyl or o-methoxy bromobenzene catalyzed by Eu2O3,
the product (3ad or 3ae) could be generated in good yield with
the aid of 1 equiv of sodium (while no product occurred
without sodium). But sodium was ineffective in promoting the
reactions of 2j, another ortho-substituted reactant, mediated by
Eu2O3, and 2a (1.5 equiv) regardless of catalysis by PPh3 or
Eu2O3. Further work would be required to further understand
the role of sodium.
Figure 1. X-ray structure of 4ea.
In order to determine if the in situ produced PhMgBr would
add to the cyano group of 1a first, benzonitrile was reacted with
2 equiv of 2a and Mg in the presence of PPh3. But the reaction
did not occur, which indicates 2a and Mg can only react with
1a with the aid of ortho hydroxyl. It is well-known that hydroxy
with an activated hydrogen is unfavorable to the nucleophilic
addition of PhMgBr. Thus, the π bond in the cyano group is
not broken by the in situ produced PhMgBr attacking first. It
could be further supported by the 69% yield of 3aa (Table 2,
entry 10) afforded in the reaction of 3 equiv of more reactive
PhMgBr (prepared in advance) with 1a. Without 2a and Mg,
the reaction of 1a did not proceed as well, which indicates the
synergistic effect of an ortho hydroxyl and 2a and Mg.
Based on these results, a plausible mechanism is proposed in
Scheme 4. Because H+ of the 1a hydroxyl and Br− have not
Scheme 4. Proposed Mechanism of 1,2-Benzisoxazole
Synthesis
Duan et al.17 reported an intermolecular [4 + 1]-annulation
pathway to similar 3-substituted benzisoxazoles. But their yields
ranged mostly from 60% to 80% including a 90% yield for
compound 3ac. Furthermore, some harsh conditions, such as
an expensive catalyst of Pd(TFA)2, the long reaction time of 20
h, a nitrogen atmosphere, and preparation of N-phenoxy-
acetamides as reactants via the copper-mediated cross-coupling
of N-hydroxy phthalimide and phenylboronic acid, were used.
Thus, we considered a more simple and efficient method.
It was interesting to afford unexpected product 1,3-diphenyl-
2H-isoindole-4,7-dione (4ea) in 51% yield from 3,6-dihydroxy-
phthalonitrile (1e) (Scheme 3). The structure of 4ea was
been captured by the styrene added in the reaction, the reaction
is to initiate by removal of the proton, which gives intermediate
B. Then the more electronegative oxygen atom of B attacks the
nitrogen atom of the cyano group to break one π bond to
provide a carbanion. Subsequently, the carbanion forms a bond
with the positive Mg in A to generate intermediate C. PPh3
interacts with the magnesium of intermediate B to form
intermediate C, which undergoes reductive elimination to
afford product 3aa similarly to a widely accepted process.23 In
order to further understand the process, bromobenzene and
Mg were reacted at 90 °C in the presence and absence of PPh3.
The yield of coupling product biphenyl was improved from
11% to 19% using PPh3, which supports the role of PPh3 in
intermediate D as well.
a
Scheme 3. Reaction of 3,6-Dihydroxyphthalonitrile (1e)
a
Isolated yield based on 1e.
unambiguously confirmed by single-crystal XRD analysis
(Figure 1). 4ea and its derivatives are one of the important
heterocyclic compounds found in numerous bioactive mole-
cules.21 To date, the preparation of 4ae is still limited by low
yields, harsh conditions, or multiple steps.21b,22 We present
herein a new route to the synthesis of isoindolediones, which is
considered to be our continued focus.
In conclusion, a novel protocol to construct a carbon−
carbon bond and 1,2-benzisoxazole scaffolds at the same time in
good to excellent yields using a Barbier−Grignard-type reaction
in one pot has been achieved. This methodology surpasses
those already described due to its mild reaction conditions, high
C
DOI: 10.1021/acs.orglett.7b00563
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Pariza, R. J.; Crowley, S. R.; Pernet, A. G.; Bunnell, P. R.; Dodge, P. W.
J. Med. Chem. 1984, 27, 1016.
(9) Nuhrich, A.; Varachelembege, M.; Renard, P.; Devaux, G. Eur. J.
efficiency, and simplicity in forming a nitrogen−oxygen bond,
which provides a novel route to heterocycle compounds. A
reasonable mechanism involving a coupling process has been
proposed.
Med. Chem. 1994, 29, 75.
(10) (a) Rangappa, K. S.; Basappa. J. Phys. Org. Chem. 2005, 18, 773.
(b) Villalobos, A.; Blake, J. F.; Biggers, C. K.; Butler, T. W.; Chapin, D.
S.; Chen, Y. L.; Ives, J. L.; Jones, S. B.; Liston, D. R.; Nagel, A. A.;
Nason, D. M.; Nielsen, J. A.; Shalaby, I. A.; White, W. F. J. Med. Chem.
1994, 37, 2721.
(11) (a) Leppik, I. E. Seizure 2004, 13, S5. (b) Murata, M.; Horiuchi,
E.; Kanazawa, I. Neurosci. Res. 2001, 41, 397.
(12) Spiteri, C.; Sharma, P.; Zhang, F.; MacDonald, S. J. F.; Keeling,
S.; Moses, J. E. Chem. Commun. 2010, 46, 1272.
(13) (a) Dubrovskiy, A. V.; Larock, R. C. Org. Lett. 2010, 12, 1180.
(b) Ma, X.; Chen, Y.; Zhang, Y.; Xu, D.; Cao, W.; Chen, J. Eur. J. Org.
Chem. 2012, 2012, 1388. (c) Crossley, J. A.; Browne, D. L. Tetrahedron
Lett. 2010, 51, 2271.
ASSOCIATED CONTENT
■
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.7b00563.
Effects of time, temperature and amount of bromoben-
zene and Mg on the reaction, control experiment,
experimental procedures, characterization data, and
NMR copies (PDF)
(14) (a) Iranpoor, N.; Firouzabadi, H.; Nowrouzi, N. Tetrahedron
Lett. 2006, 47, 8247. (b) Shelke, K. F.; Sapkal, S. B.; Shitole, N. V.;
Shingate, B. B.; Shingare, M. S. Org. Commun. 2009, 2, 72. (c) Whiting,
E.; Lanning, M. E.; Scheenstra, J. A.; Fletcher, S. J. Org. Chem. 2015,
80, 1229. (d) Jain, M.; Kwon, C.-H. J. Med. Chem. 2003, 46, 5428.
(15) (a) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovtsev, V. V.;
Noodleman, L.; Sharpless, K. B.; Fokin, V. V. J. Am. Chem. Soc. 2005,
127, 210. (b) Udd, S.; Jokela, R.; Franzen, R.; Tois, J. Tetrahedron Lett.
2010, 51, 1030. (c) Fink, D. M.; Kurys, B. E. Tetrahedron Lett. 1996,
37, 995. (d) Inamoto, K.; Katsuno, M.; Yoshino, T.; Arai, Y.; Hiroya,
K.; Sakamoto, T. Tetrahedron 2007, 63, 2695. (e) Kohler, E. P.; Bruce,
W. F. J. Am. Chem. Soc. 1931, 53, 644. (f) Yamamori, T.; Hiramatsu,
Y.; Adachi, I. J. Heterocycl. Chem. 1981, 18, 347.
(16) Duan, P.; Yang, Y.; Ben, R.; Yan, Y.; Dai, L.; Hong, M.; Wu, Y.-
D.; Wang, D.; Zhang, X.; Zhao, J. Chem. Sci. 2014, 5, 1574.
(17) (a) Lepore, S. D.; Wiley, M. R. J. Org. Chem. 1999, 64, 4547.
(b) Lepore, S. D.; Wiley, M. R. J. Org. Chem. 2000, 65, 2924. (c) Ang,
W. J.; Chu, C.-Y.; Chou, T.-C.; Lo, L.-C.; Lam, Y. Green Chem. 2013,
15, 780.
AUTHOR INFORMATION
■
Corresponding Authors
*E-mail: tytang@jnu.edu.cn.
*E-mail: tzhangym@jnu.edu.cn.
ORCID
Hong Liu: 0000-0002-2856-5930
Author Contributions
§G.C. and H.L. contributed equally.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
We are grateful to the National Natural Science Foundation of
China (Nos. 21276104, 21274083) and Jinan University
Student Innovation Program (No. 16112050) for supporting
this work.
(18) (a) Tamura, O.; Mita, N.; Imai, Y.; Nishimura, T.; Kiyotani, T.;
Yamasaki, M.; Shiro, M.; Morita, N.; Okamoto, I.; Takeya, T.;
Ishibashi, H.; Sakamoto, M. Tetrahedron 2006, 62, 12227. (b) Sun, H.;
Hu, K.; Lou, H.; Zheng, X. Energy Fuels 2008, 22, 2756.
(19) (a) Yamaguchi, K.; Fujiwara, H.; Ogasawara, Y.; Kotani, M.;
Mizuno, N. Angew. Chem., Int. Ed. 2007, 46, 3922. (b) Khalafi-Nezhad,
A.; Mohammadi, S. RSC Adv. 2014, 4, 13782.
REFERENCES
■
(1) (a) Spiteri, C.; Mason, C.; Zhang, F.; Ritson, D. J.; Sharma, P.;
Keeling, S.; Moses, J. E. Org. Biomol. Chem. 2010, 8, 2537. (b) Shelke,
A. V.; Bhong, B. Y.; Karade, N. N. Synthesis 2014, 46, 752.
(2) Dubrovskiy, A. V.; Jain, P.; Shi, F.; Lushington, G. H.; Santini, C.;
Porubsky, P.; Larock, R. C. ACS Comb. Sci. 2013, 15, 193.
(3) (a) Kesornpun, C.; Aree, T.; Mahidol, C.; Ruchirawat, S.;
Kittakoop, P. Angew. Chem., Int. Ed. 2016, 55, 3997. (b) Strupczewski,
J. T.; Allen, R. C.; Gardner, B. A.; Schmid, B. L.; Stache, U.;
Glamkowski, E. J.; Jones, M. C.; Ellis, D. B.; Huger, F. P.; Dunn, R. W.
J. Med. Chem. 1985, 28, 761. (c) Strupczewski, J. T.; Bordeau, K. J.;
Chiang, Y.; Glamkowski, E. J.; Conway, P. G.; Corbett, R.; Hartman,
H. B.; Szewczak, M. R.; Wilmot, C. A.; Helsley, G. C. J. Med. Chem.
1995, 38, 1119.
(4) (a) Gopalsamy, A.; Shi, M.; Golas, J.; Vogan, E.; Jacob, J.;
Johnson, M.; Lee, F.; Nilakantan, R.; Petersen, R.; Svenson, K. J. Med.
Chem. 2008, 51, 373. (b) Jain, M.; Kwon, C. H. J. Med. Chem. 2003,
46, 5428. (c) Benaka Prasad, S. B.; Vinaya, K.; Ananda Kumar, C. S.;
Swarup, S.; Rangappa, K. S. Invest. New Drugs 2009, 27, 534.
(5) Uno, H.; Kurokawa, M.; Masuda, Y.; Nishimura, H. J. Med. Chem.
1979, 22, 180.
(20) Wen, Y.; Chen, G.; Huang, S.; Tang, Y.; Yang, J.; Zhang, Y. Adv.
Synth. Catal. 2016, 358, 947.
(21) (a) Kel’in, A. V.; Sromek, A. W.; Gevorgyan, V. J. Am. Chem. Soc.
2001, 123, 2074. (b) Deblander, J.; Van Aeken, S.; Jacobs, J.; De
Kimpe, N.; Tehrani, K. A. Eur. J. Org. Chem. 2009, 2009, 4882.
(22) (a) Gilgen, P.; Jackson, B.; Hansen, H. J.; Heimgartner, H.;
Schmid, H. Helv. Chim. Acta 1974, 57, 2634. (b) Likussar, W.;
Michelitsch, A.; Schubert-Zsilavecz, M.; Gusterhuber, D. Monatsh.
Chem. 1991, 122, 987. (c) Huang, H. M.; Gao, J. R.; Hou, L. F.; Jia, J.
H.; Han, L.; Ye, Q.; Li, Y. J. Tetrahedron 2013, 69, 9033.
(23) (a) Okamoto, K.; Housekeeper, J. B.; Luscombe, C. K. Appl.
Organomet. Chem. 2013, 27, 639. (b) Shekhar, S.; Hartwig, J. F. J. Am.
Chem. Soc. 2004, 126, 13016.
(6) (a) Priya, B. S.; Basappa; Nanjunda Swamy, S.; Rangappa, K. S.
Bioorg. Med. Chem. 2005, 13, 2623. (b) Suhas, R.; Chandrashekar, S.;
Gowda, D. C. Eur. J. Med. Chem. 2011, 46, 704.
(7) Vaidya, S. D.; Kumar, B. V. S.; Kumar, R. V.; Bhise, U. N.;
Mashelkar, U. C. J. Heterocycl. Chem. 2007, 44, 685.
(8) (a) Shutske, G. M.; Setescak, L. L.; Allen, R. C.; Davis, L.;
Effland, R. C.; Ranbom, K.; Kitzen, J. M.; Wilker, J. C.; Novick, W. J. J.
Med. Chem. 1982, 25, 36. (b) Plattner, J. J.; Fung, A. K. L.; Parks, J. A.;
D
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