A biomimetic approach to lanthionines

Article abstract of DOI:10.1021/ol203068s

The asymmetric sulfa-Michael additions of appropriately protected l- and d-cysteine derivatives to new chiral dehydroamino acid derivatives have been developed as key steps in the synthesis of biologically important cysteine derivatives, such as lanthionine (Lan) and β-methyllanthionine (MeLan), which are unusual bis-α-amino acids found in the emerging lantibiotics such as nisin.

Full text of DOI:10.1021/ol203068s

ORGANIC
LETTERS
2012
Vol. 14, No. 1
334–337
A Biomimetic Approach to Lanthionines
†
ꢀ
ꢀ
Carlos Aydillo, Alberto Avenoza,* Jesus H. Busto, Gonzalo Jimenez-Oses,
ꢀ
ꢀ
Jesus M. Peregrina,* and Marıa M. Zurbano
´
´
Departamento de Quımica, Universidad de La Rioja, Centro de Investigacion en Sıntesis
Quımica, U.A.-C.S.I.C., E-26006 Logrono, Spain
ꢀ
´
´
~
*alberto.avenoza@unirioja.es; jesusmanuel.peregrina@unirioja.es
Received November 17, 2011
ABSTRACT
The asymmetric sulfa-Michael additions of appropriately protected L- and D-cysteine derivatives to new chiral dehydroamino acid derivatives have
been developed as key steps in the synthesis of biologically important cysteine derivatives, such as lanthionine (Lan) and β-methyllanthionine
(MeLan), which are unusual bis-R-amino acids found in the emerging lantibiotics such as nisin.
One of the most important features of the natural amino
acid cysteine (Cys) is related to the nucleophilicity of its SH
moiety. For example, this thiol group can stabilize the
tertiary structure of significant bioactive peptides, due to
its participation in disulfide bonds, as well as play an
important role as a nucleophile in Michael-type reactions
onto dehydroamino acids to generate peptide sequences.1
In this sense, significant lantibiotics as nisin, duramycin,
and subtilin2 contain in their structures lanthionine or
methyllanthionines, which are unusual bis-R-amino acids
that consist of two alanyl residues bridged by a thioether
linkage. The biosynthetic origin of these structural features
involves the initial dehydration of specific Ser and Thr
residues in the prelantibiotic peptide and the subsequent
stereoselective enzyme-mediated Michael addition of cys-
teine thiols to the newly formed dehydroalanine (Dha)
and dehydrobutyrine (Dhb) residues, respectively3 (Figure
S1, Supporting Information (SI)). In contrast to the labile
disulfide bond of cystine, the monosulfur bridge oflanthio-
nine derivatives is chemically far stronger. For this reason,
thioether-bridged peptides4,5 have therefore been incorpo-
rated into medicinally relevant peptides.
On the other hand, taking into account that the increas-
ing problem of antibiotic resistance has highlighted the
imperative demand for novel antimicrobial agents, pep-
tides containing the thioether bridge, such as lantibiotics,
have emerged as important tools to address this problem.6
A convenient strategy toward the synthesis of lantibiotics
(3) (a) Li, B.; Yu, J. P. J; Brunzelle, J. S.; Moll, G. N.; van der Donk,
W. A.; Nair, S. K. Science 2006, 311, 1464. (b) Goto, Y.; Li, B.; Claesen,
J.; Shi, Y.; Bibb, M. J.; van der Donk, W. A. PLoS Biol. 2010, 8,
e1000339. (c) You, Y. O.; Levengood, M. R.; Ihnken, L. A. F.; Knowl-
ton, A. K.; van der Donk, W. A. ACS Chem. Biol. 2009, 4, 379. (d) Goto,
€
Y.; Okesli, A.; van der Donk, W. A. Biochemistry 2011, 50, 891. (e) Jung,
† Present address: University of California, Los Angeles, Department of
Chemistry and Biochemistry, Los Angeles, CA 90095-1569, United States.
(1) (a) Jocelyn, P. C. Biochemistry of the SH Group. The Ocurrence,
Chemical Properties, Metabolism and Biological Functions of Thiols and
Disulfides; Academic Press: New York. 1972. (b) Bulaj, G.; Kortemme, T.;
Goldenberg, D. P. Biochemistry 1998, 37, 8965. (c) Brotzel, F.; Mayr, H.
Org. Biomol. Chem. 2007, 5, 3814.
G. Angew. Chem., Int. Ed. 2006, 45, 5919.
€
(4) (a) Osapay, G.; Prokai, L.; Kim, H.-S.; Medzihradszky, K. F.;
Coy, D. H.; Liapakis, G.; Reisine, T.; Melacini, G.; Zhu, Q.; Wang, S.
H.-H.; Mattern, R.-H.; Goodman, M. J. Med. Chem. 1997, 40, 2241. (b)
€
Melacini, G.; Zhu, Q.; Osapay, G.; Goodman, M. J. Med. Chem. 1997,
40, 2252. (c) Matteucci, M.; Bhalay, G.; Bradley, M. Tetrahedron Lett.
2004, 45, 1399.
(5) (a) Yu, L.; Lai, Y.; Wade, J. V.; Coutts, S. M. Tetrahedron Lett.
1998, 39, 6633. (b) Feng, Y.; Pattarawarapan, M.; Wang, Z.; Burgess, K.
Org. Lett. 1999, 1, 121. (c) Rew, Y.; Malkmus, S.; Svensson, C.; Yaksh,
T. L.; Chung, N. N.; Schiller, P. W.; Cassel, J. A.; DeHaven, R. N.;
Goodman, M. J. Med. Chem. 2002, 45, 3746. (d) Mustapa, M. F. M.;
Harris, R.; Mould, J.; Chubb, N. A. L.; Schultz, D.; Driscoll, P. C.;
Tabor, A. B. Tetrahedron Lett. 2002, 43, 8363.
(6) (a) Moll, G. N.; Kuipers, A.; Rink, R. Antonie van Leeuwenhoek
2010, 97, 319. (b) Field, D.; Hill, C.; Cotter, P. D.; Ross, R. P. Mol.
Microbiol. 2010, 78, 1077.
(2) Reviews: (a) Guder, A.; Wiedemann, I.; Sahl, H.-G. Biopolymers
2000, 55, 62. (b) van Kraaij, C.; de Vos, W. M.; Siezen, R. J.; Kuipers,
O. P. Nat. Prod. Rep. 1999, 16, 575. (c) Breukink, E.; de Kruijff, B.
Biochim. Biophys. Acta 1999, 1462, 223. (d) Sahl, H.-G.; Bierbaum, G.
Annu. Rev. Microbiol. 1998, 52, 41. (e) Jung, G. Angew. Chem., Int. Ed.
Engl. 1991, 30, 1051. (f) Chatterjee, Ch.; Paul, M.; Xie, L.; van der Donk,
W. A. Chem. Rev. 2005, 105, 633 and references cited therein. (g) Patton,
G. C.; van der Donk, W. A. Curr. Opin. Microbiol. 2005, 8, 543. (h) Jack,
R. W.; Jung, G. Curr. Opin. Chem. Biol. 2000, 4, 310. (i) Ross, A. C.;
Vederas, J. C. J. Antibiot. 2011, 64, 27.
r
10.1021/ol203068s
Published on Web 12/16/2011
2011 American Chemical Society

involves the incorporation of orthogonally protected
lanthionines as building blocks in their solid-phase
synthesis.7 Therefore, several synthetic approaches to
lanthionine (Lan) and β-methyllanthionine (MeLan)
monomers have been described in recent years.2,8 More-
over, the synthesis of isomers namely norlanthionines (nor-
Lan)9 and R-methylnorlanthionines (R-Me-nor-Lan),10
which consist of an alanyl and a β-alanyl or a R-methyl-
β-alanyl residues, respectively, have beenreported andnor-
Lan has been incorporated in a cyclic peptide analog of the
ring C of lantibiotic nisin.11
Taking into account the importance of these bis-R-
amino acids, the development of a new and efficient
synthesis of these systems seems to be of interest. Herein,
we report a biomimetic approach to Lan and MeLan
exploiting the high nucleophilicity of the sulfhydryl group
of Cys in a stereoselective Michael reaction of the con-
venient protected cysteine derivative onto chiral dehydro-
alanine and dehydrobutyrine methyl esters (Figure S1, SI).
Despite being one ofthe mostimportant and widely used
synthetic tools in organic synthesis,12 there are relatively
few reports on the use of the Michael addition of nucleo-
philes to chiral R,β-dehydroamino acids,13 and in most
cases chirality is present in both amino and carboxylic acid
groups, involving cyclic systems such as oxazolidinones or
dehydrodiketopiperazines.14
sulfa-Michael additions onto chiral dehydroamino acids.16
The use of Michael additions of cysteine onto Dha/Dhb in
linear lantibiotic precursors (in the absence of enzymes) is
well documented16dÀg and these reactions frequently are
stereoselective when a “natural” linear sequence is used.
Likely, the closest work to the present study is the con-
vergent synthesis of peptide conjugates using the dehy-
droalanine moiety of several dehydropeptides for
chemoselective ligations; however no asymmetric induc-
tion by the chiral backbone of the peptide was observed in
the protonation of the enolate intermediate formed by the
initial Michael addition.17
Figure 1. Dehydroamino acids 1, 2, and 3.
We recently reported an efficient synthesis of chiral
dehydroamino acid derivatives 1À3 as potential chiral
building blocks for the Michael addition18 (Figure 1).
Now, in this communication, their absolute configurations
are confirmed by X-ray analysis (Figure S2, SI). It is
important to highlight that, while several chiral dehydro
amino acids have been used for developing stereoselective
Michael reactions,16,19 there are few examples concerning
chiral building blocks in which the dehydroamino acid
displays chirality exclusively in the amino moiety, as a
chiral enecarbamate.20
In particular, several approaches have been documented
for diastereo- and enantiocontrol in the conjugate addition
of sulfur-based nucleophiles toMichael acceptors,15 and to
the best of our knowledge, there are only a few examples of
(7) (a) Bregant, S.; Tabor, A. B. J. Org. Chem. 2005, 70, 2430. (b)
Ross, A. C.; Liu, H.; Pattabiraman, V. R.; Vederas, J. C. J. Am. Chem.
Soc. 2010, 132, 462. (c) Galande, A. K.; Spatola, A. F. Lett. Pept. Sci.
2002, 8, 247. (d) Mothia, B.; Appleyard, A. N.; Wadman, S.; Tabor,
A. B. Org. Lett. 2011, 13, 4216.
(16) (a) Saghiyan, A. S.; Geolchanyan, A. V.; Djamgaryan, S. M.;
Vardapetyan, S. M.; Tararov, V. I.; Kuz’mina, N. A.; Ikonnikov, N. S.;
Belokon, N. Y.; North, M. Russ. Chem. Bull. 2000, 49, 1460.
(b) Saghiyan, A. S.; Stepanyan, L. A.; Manasyan, L. L.; Geolchanyan,
A. V.; Djamgaryan, S. M.; Ajvazyan, H. R.; Panosyan, H. A.; Maleev,
V. I.; Saveleva, T. F. Tetrahedron: Asymmetry 2010, 21, 2638.
(8) Some examples: (a) Narayan, R. S.; VanNieuwenhze, M. S. Org.
Lett. 2005, 7, 2655. (b) Swali, V.; Matteucci, M.; Elliot, R.; Bradley, M.
Tetrahedron 2002, 58, 9101. (c) Zhu, X.; Schmidt, R. R. Eur. J. Org.
€
Chem. 2003, 4069. (d) Shao, H.; Wang, S. H.; Lee, C.; Osapay, G.;
€
Goodman, M. J. Org. Chem. 1995, 60, 2956. (e) du Vigneaud, B. J. Biol.
Chem. 1941, 138, 151–154. (f) Wakamiya, T.; Oda, Y.; Fukase, K.;
Shiba, T. Bull. Chem. Soc. Jpn. 1985, 58, 536. (g) Cobb, S. L.; Vederas,
J. C. Org. Biomol. Chem. 2007, 5, 1031. (h) Martin, N. I. J. Org. Chem.
(c) Schmidt, U.; Ohler, E. Angew. Chem., Int. Ed. Engl. 1976, 15, 42.
(d) Burrage, S.; Raynham, T.; Williams, G.; Essex, J. W.; Allen, C.;
Cardno, M.; Swali, V.; Bradley, M. Chem.;Eur. J. 2000, 6, 1455.
(e) Zhu, Y.; Gieselman, M. D.; Zhou, H.; Averin, O.; van der Donk,
W. A. Org. Biomol. Chem. 2003, 1, 3304. (f) Polinsky, A.; Cooney, M. G.;
€
2009, 74, 946. (i) Seyberth, T.; Voss, S.; Brock, R.; Wiesmuller, K.-H.;
€
Jung, G. J. Med. Chem. 2006, 49, 1754. (j) Smith, N. D.; Goodman, M.
Org. Lett. 2003, 5, 1035.
Toy-Palmer, A.; Osapay, G.; Goodman, M. J. Med. Chem. 1992, 35, 4185.
(g) Paul, M.; van der Donk, W. A. Mini-Rev. Org. Chem. 2005, 2, 23.
(17) (a) Zhu, Y.; van der Donk, W. A. Org. Lett. 2001, 3, 1189. (b)
Galonic, D. P.; van der Donk, W. A.; Gin, D. Y. Chem.;Eur. J. 2003, 9,
5997.
(9) (a) Mustapa, M. F. M.; Harris, R.; Mould, J.; Chubb, N. A. L.;
Schultz, D.; Driscoll, P. C.; Tabor, A. B. Tetrahedron Lett. 2002, 43,
8363. (b) Mustapa, M. F. M.; Harris, R.; Bulic-Subanovic, N.; Elliott,
S. L.; Bregant, S.; Groussier, M. F. A.; Mould, J.; Schultz, D.; Chubb,
N. A. L.; Gaffney, P. R. J.; Driscoll, P. C.; Tabor, A. B. J. Org. Chem.
2003, 68, 8185.
ꢀ
ꢀ
(18) (a) Aydillo, C.; Avenoza, A.; Busto, J. H.; Jimenez-Oses, G.;
Peregrina, J. M.; Zurbano, M. M. Tetrahedron: Asymmetry 2008, 19,
ꢀ
ꢀ
2829. (b) Aydillo, C.; Jimenez-Oses, G.; Busto, J. H.; Peregrina, J. M.;
ꢀ
ꢀ
(10) Avenoza, A.; Busto, J. H.; Jimenez-Oses, G.; Peregrina, J. M.
Org. Lett. 2006, 8, 2855.
Zurbano, M. M.; Avenoza, A. Chem.;Eur. J. 2007, 13, 4840.
ꢀ
´
(19) Cativiela, C.; Dıaz-de-Villegas, M. D.; Galvez, J. A. Can. J.
Chem. 1992, 70, 2325.
(11) Mustapa, M. F. M.; Harris, R.; Esposito, D.; Chubb, N. A. L.;
Mould, J.; Schultz, D.; Driscoll, P. C.; Tabor, A. B. J. Org. Chem. 2003,
68, 8193.
(12) Perlmutter, P. Conjugate Addition Reactions in Organic Synth-
esis; Pergamon Press: Oxford, U.K., 1992.
(20) For recents reviews on the use of enecarbamates in stereoselec-
tive synthesis, see: (a) Matrubara, R.; Kobayashi, S. Acc. Chem. Res.
2008, 41, 292. (b) Gopalaiah, K.; Kagan, H. B. Chem. Rev. 2011, 111,
4599. For an example of asymmetric conjugate addition using a chiral
enecarbamate similar to that shown in this paper, see: (c) Lander, P. A.;
Hegedus, L. S. J. Am. Chem. Soc. 1994, 116, 8126.
(13) (a) Schmidt, U.; Lieberknecht, A.; Wild, J. Synthesis 1988, 159.
€
(b) Bonauer, C.; Walenzyk, T.; Konig, B. Synthesis 2006, 1.
(14) (a) Javidan, A.; Schafer, K.; Pyne, S. G. Synlett 1997, 100.
(b) Pyne, S. G.; Javidan, A.; Skeleton, B. W.; White, A. H. Tetrahedron
1995, 51, 5157. (c) Bull, S. D.; Davies, S. G.; O’Shea, M. D. J. Chem.
Soc., Perkin Trans. 1 1998, 3657. (d) Bull, S. D.; Davies, S. G.; Garner,
A. C.; O’Shea, M. D. J. Chem. Soc., Perkin Trans. 1 2001, 3281.
(21) (a) Ferreira, P. M. T.; Maia, H. L. S.; Monteiro, L. S.;
Sacramento, J.; Sebastiao, J. J. Chem. Soc., Perkin Trans. 1 2000,
3317. (b) Ferreira, P. M. T.; Maia, H. L. S.; Monteiro, L. S.; Sacramento,
J. J. Chem. Soc., Perkin Trans. 1 2001, 3167. (c) Abreu, A. S.; Silva,
N. O.; Ferreira, P. M. T.; Queiroz, M.-J. R. P. Eur. J. Org. Chem. 2003,
1537. (d) Naidu, B. N.; Sorenson, M. E.; Connolly, T. P.; Ueda, Y.
J. Org. Chem. 2003, 68, 10098.
€
(15) (a) Enders, D.; Luttgen, K.; Narine, A. A. Synthesis 2007, 959.
€
(b) Krause, N.; Hoffmann-Roder, A. Synthesis 2001, 171.
Org. Lett., Vol. 14, No. 1, 2012
335

To demonstrate the potential synthetic use of these
systems as new chiral building blocks, we performed the
Michael reaction of dehydroalanine 1 with commercial S-
nucleophiles, such as propane-1-thiol, cyclohexanethiol,
tert-butylthiol, and thiophenol21 (Table 1).
Scheme 1. Synthesis of S-Propyl- and S-Phenylcysteines
Table 1. Michael Reactions between Chiral Dehydroalanine 1
and Different S-Nucleophiles
Scheme 2. Synthesis of meso-Lanthionine
Time
(min)
Yield
(%)a
entry
R
compd
dr
1
2
3
4
Pr
4
5
6
7
15
60
180
60
95
86
82
73
>95:5
>95:5
>95:5
>95:5
Cy
tBu
Ph
a Yield of products after column chromatography.
We started our experiments using THF as a solvent in
the presence of DBU as a base to generate in situ the
corresponding thiolates. Initially and using these condi-
tions, we assayed the Michael reaction of dehydroalanine 1
with propane-1-thiol at 0 °C, giving a mixture of two
isomers. Therefore, we carried out the reaction at
À78 °C, giving, after 15 min, exclusively one product
corresponding to structure 4. The diastereomeric ratio
1
(dr) was assumed to be >95:5, because in the H NMR
spectrum corresponding to the crude of the reaction only
one diastereoisomer was observed. After column chroma-
tography, 4 was obtained in a 95% yield (entry 1, Table 1).
Similar features were observed when cyclohexanethiol,
tert-butanethiol, and thiophenol were used as S-nucleo-
philes giving compounds 5, 6, and 7, respectively (entries 2,
3, and 4, Table 1). The sole difference was the slight
decrease in yield of the reactions, probably due to the steric
volume of these nucleophiles.
The absolute configuration of the Michael adduct 6 was
determined unambiguously by X-ray analysis, showing the
new sterocenter created in the Michael reaction an (R)-
configuration (Figure S3, SI).
In the cases of 4 and 7, the absolute configurations of
the new stereocenters were determined by transformation
of these compounds into the well-known amino acids
S-propylcysteine 8 and S-phenylcysteine 9, respectively,
and comparing the optical rotations measured with those
appeared in the literature.22 These transformations were
carried out using acid hydrolysis in an aqueous 6 N HCl
solution at reflux, followed by treatment with propylene
oxide in ethanol (Scheme 1).
L- and D-cysteine derivatives as S-nucleophiles and dehy-
droalanine 1 as the Michael acceptor.23 Therefore, N-Boc-
L-cysteine methyl ester 10 was reacted with chiral Michael
acceptor 1 using DBU as a base and THF as a solvent at
À78 °C for 30 min, giving exclusively compound 11, a
protected Lan, in an excellent yield (90%) with a dr >95:5,
as we determined by 1H NMR spectroscopy (Scheme 2).
Scheme 3. Michael Reaction between Chiral β-Substituted
Dehydrobutyrine 2 and Cyclohexanethiol
Nevertheless, in the case of N-Boc-D-cysteine methyl
ester 12, because it is not commercially available, it had to
In view of the excellent results obtained in these pre-
liminary reactions, we assayed the Michael reaction with
(23) For an early nonstereoselective version of this reaction, see:
Probert, J. M.; Rennex, D.; Bradley, M. Tetrahedron Lett. 1996, 37,
1101.
(22) (a) Stoll, A.; Seebeck, E. Helv. Chim. Acta 1948, 31, 189. (b) Dua,
R. K.; Taylor, E. W.; Phillip, R. S. J. Am. Chem. Soc. 1993, 115, 1264.
336
Org. Lett., Vol. 14, No. 1, 2012

Scheme 4. Stereodivergent Syntheses of MeLan 18 and 19 Using a Chiral Sulfa-Michael Addition as a Key Step
be synthesized following the published procedure,24 start-
ing from D-cystine, whose amino and carboxylic acid
groups were protected as Boc and methyl ester, respec-
tively. Cleavage of the disulfide bond with tri-n-butylphos-
phine (Bu3P) gave the corresponding D-cysteine derivative
12, which was used as an S-nucleophile with dehydroal-
anine 1 in the Michael reaction, giving exclusively one
product corresponding to the compound 13 (Scheme 2).
Both chiral precursors of Lan 11 and 13 were subjected to
acid hydrolysis giving, surprisingly, the same compound,
the bioactive meso-lanthionine (meso-Lan) (Scheme 2).
With these hydrolysis experiments we could assert the
absolute configurations of the new stereocenters created in
both double asymmetric Michael additions.8e Thus, a chiral
S-nucleophile of (R)-configuration induces an (S)-config-
uration in the new stereocenter, while the use of a chiral S-
nucleophile of (S)-configuration induces an (R)-configura-
tion in the new stereocenter. Thus, this procedure allowed us
the easy synthesis of bioactive meso-Lan using, as a key step,
the double asymmetric S-Michael reaction between a chiral
dehydroalanine and L- or D-cysteine derivatives.
carrying out the reactions under the same conditions used
above (Scheme 4).
Although the yield of the reactions slightly decreased to
57% and 61% for the products 16 and 17, respectively, the
diastereoselectivities achieved were excellent, since in each
case only one product was obtained out of the four
possibilities. In both cases the induction of diastereoselec-
tivity was the same, producing (S,S)-configurations in the
two new stereocenters created. These Michael adducts
were easily transformed, by acid hydrolysis, into the
corresponding MeLan 18 and 19 (Scheme 4). This fact
allowed us to confirm the absolute configurations of the
stereocenters created in the Michael additions,8f which
corresponded to (S,S).
Taking into account the different behaviors of S-nucleo-
philes in these Michael reactions and the inherent difficulty
in predicting the stereochemical outcome, in future works
we will undertake an extensive mechanistic and theoretical
study to elucidate first the role of the β-substitution in the
chiral dehydroamino acid building block and also the role
of chirality in the S-nucleophile.
In a further step and to check the effect of the β-
substitution in the chiral Michael acceptor, we planned to
expand this reactivity to the β-substituted dehydroamino
acid 2. Therefore, we carried out the Michael addition of
dehydrobutyrine 2 and cyclohexanethiol as an S-nucleo-
phile using THF as a solvent and DBU as a base. After the
reaction was stirred for 4 h, only one diastereoisomer
(compound 15) was obtained with a 77% yield (Scheme 3).
The absolute configuration of 15 could be determined
unambiguously by X-ray analysis, showing the (S,S)-
configuration of two new sterocenters created in the
Michael reaction (Figure S4, SI).
In summary, we have carried out the stereoselective
synthesis of bioactive meso-Lan (14) and optically active
MeLans(18and 19), all ashydrochloridederivatives, using
a straightforward strategy based on the double asymmetric
sulfa-Michael addition of L- and D-cysteine derivatives
onto chiral dehydroamino acid derivatives 1 and 2, which
could be considered as a biomimetic approach.
Acknowledgment. We thank the Ministerio de Ciencia e
ꢀ
Innovacion (Project CTQ2009-13814/BQU), Gobierno de
La Rioja (Colabora-2010/05), the Universidad deLa Rioja
(project EGI-10/65), and CSIC (fellowship to C.A.).
With this excellent result in hand, we decided to study
the double asymmetric Michael additions between this
chiral dehydrobutyrine 2 and the protected cysteines 10
and 12 as a source of β-methyllanthionines (MeLan),
Supporting Information Available. Experimental de-
tails, as well as spectroscopic characterization of all new
compounds and X-ray data for compounds 1, 3, 6, and 15.
This material is available free of charge via the Internet at
http://pubs.acs.org.
ꢀ
(24) Dugave, C.; Menez, A. Tetrahedron: Asymmetry 1997, 8, 1453.
Org. Lett., Vol. 14, No. 1, 2012
337