Total synthesis and antifungal activity of (2S,3R)-2-aminododecan-3-ol

Article abstract of DOI:10.1016/j.bmcl.2012.05.082

We report the total synthesis of (2S,3R)-2-aminododecan-3-ol has been achieved starting from commercially available 10-undecenoic acid. The key steps involved are Sharpless asymmetric epoxidation, Miyashita's boron-directed C-2 regioselective azidolysis, generated the asymmetric centers and in situ detosylation and reduction of azido tosylate. The antifungal activity of the synthesized (2S,3R)-2-aminododecan-3-ol was evaluated on several Candida strains and was comparable to miconazole, a standard drug.

Full text of DOI:10.1016/j.bmcl.2012.05.082

Bioorganic & Medicinal Chemistry Letters 22 (2012) 4678–4680
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Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Total synthesis and antifungal activity of (2S,3R)-2-aminododecan-3-ol
T. Vijai Kumar Reddy a, B. L. A. Prabhavathi Devi a, , R. B. N. Prasad a, M. Poornima b, C. Ganesh Kumar b
⇑
a Centre for Lipid Research, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 607, India
b Chemical Biology Laboratory, CSIR-Indian Institute of Chemical Technology, Uppal Road, Hyderabad 500 607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
We report the total synthesis of (2S,3R)-2-aminododecan-3-ol has been achieved starting from commer-
cially available 10-undecenoic acid. The key steps involved are Sharpless asymmetric epoxidation,
Miyashita’s boron-directed C-2 regioselective azidolysis, generated the asymmetric centers and in situ
detosylation and reduction of azido tosylate. The antifungal activity of the synthesized (2S,3R)-2-amino-
dodecan-3-ol was evaluated on several Candida strains and was comparable to miconazole, a standard
drug
Received 14 February 2012
Revised 11 May 2012
Accepted 22 May 2012
Available online 30 May 2012
Keywords:
10-Undecenoic acid
Wittig reaction
Ó 2012 Elsevier Ltd. All rights reserved.
Sharpless asymmetric epoxidation
Miyashita’s azidolysis
Antifungal
Natural products have played an important role in the history of
drug discovery and development process by providing novel, clin-
ically useful medicines having various biological activities such as
anticancer, anathematic, antifungal, anti-protozoal and antimicro-
bial activities, among others.1,2 In the last decades, natural prod-
ucts having antifungal activity received increased attention from
chemists since fungal infections are very common. So there is al-
ways an ever increasing requirement of safe and effective anti-
fungal agents to control fungal infections. The importance of
antifungal chemotherapy continues to evolve rapidly because inva-
sive fungal infections in immuno-compromised patients have be-
come increasingly significant. Recently, new antifungal agents,
such as voriconazole and caspofungin,3 have entered the clinical
arena. Ongoing efforts towards the search for new natural anti-
fungal agents from marine organisms have been recently re-
viewed.4 (2S,3R)-2-Aminododecan-3-ol (1), is a natural product
isolated from the ascidian Clavelina oblonga,1 which showed strong
(2S,3R)-2-aminododecan-3-ol isolated from C. oblonga were found
to have (2S,3R)-configuration. Due to the unusual stereochemical
configuration of these natural products and the potent biological
activity, we were interested in developing an efficient route for
their synthesis. Owing to its structural simplicity, the title com-
pound 1 has been less investigated in terms of its total synthesis.
Sutherland reported the total synthesis of 1 from (S)-glycidol in
14 steps with an overall yield of 29%.9 Very recently, Huang re-
ported an improved four-step approach for the stereoselective syn-
thesis of long-chain anti-2-amino-3-alkanols from
L-alanine
derivatives.10 In this context, we report a new synthetic approach
involving 10 steps for the synthesis of (2S,3R)-2-aminododecan-
3-ol from a cheaper and readily available 10-undecenoic acid,
which is being produced from a renewable feedstock, castor oil.
The synthesized (2S,3R)-2-aminododecan-3-ol (1) was evaluated
for antifungal activity on a series of Candida strains.
The retrosynthetic strategy for the total synthesis of the target
molecule 1 is delineated in Scheme 1. We envisaged that the target
molecule 1 could be obtained from azido tosylate 11 which in turn
could be derived from azido diol 9. The compound 9 could be
activity against Candida albicans (MIC of 0.7
l
g mLꢀ1) and moder-
g mLꢀ1). Mar-
ately active against Candida glabrata (MIC of 30
l
ine-derived long chain 2-amino-3-alkanols, are commonly
encountered in tunicates and some sponges.5 Structurally, these
compounds are related to the sphingosine derivatives (e.g., sphin-
ganine, 4-sphinganine, phytosphingosine), long known as central
structural element of sphingolipids, which are important constitu-
ents of the lipid portion of cell membranes in living organisms.
OH
OH
OH
O
R
R
OTs
R
OH
R
OH
NH2
N3
N3
(1)
(8)
The carbon chain length of these sphingolipid derivatives vary
(11)
(9)
O
6,7
from C12 to C30
.
Sphingolipids8 and 2-amino-3-alkanols such as
CO2Et
( )
( )
R= n-C9H19
HO
R
HO
8
8
(6)
(3)
(2)
⇑
Corresponding author. Tel.: +91 40 27191515; fax: +91 40 27193370.
E-mail address: prabhavathi@iict.res.in (B.L.A. Prabhavathi Devi).
Scheme 1. Retrosynthetic analysis of (2S,3R)-2-aminododecan-3-ol.
0960-894X/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.bmcl.2012.05.082

T. Vijai Kumar Reddy et al. / Bioorg. Med. Chem. Lett. 22 (2012) 4678–4680
4679
Table 1
obtained from enantiomerically pure epoxy alcohol 8 by the trial-
Antifungal activity of (2S,3R)-2-aminododecan-3-ol
kyl borate mediated C-2 selective azidolysis under Miyashita’s con-
dition. The fragment 8 could be prepared from the intermediate 6
by involving Sharpless asymmetric epoxidation reaction. The inter-
mediate 6 could in turn be prepared from the intermediate 3 by
involving ozonolysis followed by Wittig reaction.
Thus as per the retrosynthesis shown above, the first sub-target
for the synthesis of 1 was to synthesize enantiomerically pure
epoxy alcohol 8. Our strategy for the synthesis of 1 started with
readily available fatty acid namely, 10-undecenoic acid 2. Accord-
ing to Scheme 2, the fatty acid 2 was treated with LiAlH4 to afford
the alcohol 3 in high yield (97%).11 The free hydroxymethyl group
at C1 in compound 3 was converted into methyl group by tosyla-
tion12 of the primary alcohol 3 in the presence of triethylamine
and subsequent treatment of the tosyloxy derivative 4 with LiAlH4
to afford the desired olefin 5 with 84% yield.13,14
Test strains
MIC (
l
g mLꢀ1
Mb
)
C (1)a
Fc
Nd
Ae
Candida parapsilosis MTCC 1744
Candida aaseri MTCC 1962
Candida glabrata MTCC 3019
Candida albicans MTCC 183
Candida albicans MTCC 7315
Candida albicans MTCC 3958
Candida albicans MTCC 854
4.9
9.9
9.9
9.9
9.9
9.9
9.9
9.9
9.9
9.9
9.9
9.9
18.8
75.0
75.0
37.5
37.5
75.0
37.5
150
150
150
150
150
150
150
300
300
300
300
300
300
300
19.8
37.5
a
b
c
C (1): compound (1).
M: miconazole.
F: fluconazole.
N: nystatin.
A: amphotericin B.
d
e
Ozonolysis of 5 provided 1-decanal and was used directly in the
subsequent Wittig reaction without further purification to avoid
decomposition.15 According to Barrett,19a 1-decanal was treated
Antifungal activity: In the present study, the antifungal activity
(Table 1) of the synthesized (2S,3R)-2-aminododecan-3-ol (1)
with Ph3P@CHCO2Et in dry THF gave exclusively E-
ester 6 in 86% yield (over two steps).16 Reduction of 6 with DIBAL-
H in dry DCM furnished the desired E- ,b-unsaturated alcohol 7 in
high yield (90%).14,16–18 Sharpless asymmetric epoxidation19b of 7
with
-(ꢀ)-diethyl tartrate afforded enantiomerically pure epoxy
a,b-unsaturated
was carried out using well diffusion method.21,22
As shown in Table 1, the synthesized (2S,3R)-2-aminododecan-
3-ol 1 exhibited moderate activity towards C. albicans MTCC 854
and C. albicans MTCC 3958, while it showed good activity (MIC of
a
D
9.9
183, C. glabrata MTCC 3019 and C. aaseri MTCC 1962 and very high
inhibitory activity (MIC of 4.9
g mLꢀ1) towards C. parapsilosis
l
g mLꢀ1) towards C. albicans MTCC 7315, C. albicans MTCC
alcohol 8 in 90% yield with >98% ee by 1H NMR analysis of the cor-
responding Mosher ester derivative. C-2 selective azidolysis20 of
enantiomerically pure epoxide 8 by sodium azide in dry DMF in
the presence of trimethylborate furnished mixture of azido diols
9 (major) and 10 (minor). These two regioisomers did not show
any separation on TLC, and an attempt to purify by column chro-
matography was also unsuccessful. However, the corresponding
tosylates 11 and 12, which were obtained by tosylation of a mix-
ture of 9 and 10 with 1.1 equiv of tosyl chloride in dry CH2Cl2 in
the presence of triethylamine at 0 °C, were completely separable
by silica gel column chromatography. Amounts of isolated 11 and
12 suggested that in the azidolysis reaction compounds 9 and 10
were formed in a ratio of 84:16. The synthesis of (2S,3R)-2-amino-
dodecan-3-ol 1 was completed by one-pot reduction of azido tos-
ylate17 11 with LiAlH4 involving simultaneous reduction of –N3
to –NH2 and detosylation with 68% yield. The overall yield of the
(2S,3R)-2-aminododecan-3-ol 1 was found to be 17.1% after 10
steps. Spectral data of some selected compounds namely, 8, 11
and 1 are given in Ref. 23.
l
MTCC 1744, demonstrating that the amine and hydroxyl groups
present in this target molecule 1 plays a key role in the struc-
ture–function relationship in exhibiting this bioactivity. Further,
the antifungal activity exhibited by (2S,3R)-2-aminododecan-3-ol
1 against these strains is comparatively better than the antifungal
activity exhibited by different clinically used antifungal drugs like
miconazole (MIC of 9.9
between 18.8 and 75
g mLꢀ1), nystatin (MIC of 150
amphotericin B (MIC of 300
g mLꢀ1). While, in an earlier study1 it
was reported that the naturally derived (2S,3R)-2-aminododecan-
l
g mLꢀ1), fluconazole (MIC values ranging
l
l
g mLꢀ1) and
l
3-ol
1 exhibited strong activity against C. albicans (MIC of
0.7
30
l
l
g mLꢀ1) and moderate activity against C. glabrata (MIC of
g mLꢀ1). This activity was comparable to the antifungal activ-
ity of standard antifungal drugs like nystatin (MIC values ranging
between 1.0 and 4.0
l
g mLꢀ1) and ketoconazole (MIC between
0.01 and 1
l
g mLꢀ1).
O
a
b
c
d
HO ( )
HO ( )
TsO ( )
CO2Et e
( )
( )
8
8
8
7
7
(5)
(2)
(3)
(4)
(6)
OH
N3
O
h
f
g
( )
( )
( )
( )
OH
OH
OH
OH
+
7
7
7
7
OH
N3
(7)
(8)
(9)
(10)
inseparable mixture
OH
N3
OH
OH
i
j
( )
( )
( )
OTs
OTs
OTs
+
( )
7
7
7
N3
N3
OH
8
NH2
(11)
(12)
(11)
(1)
separable mixture
Scheme 2. Reagents and conditions: (a) LiAlH4, dry THF, 0 °C to rt, 30 min, 97%; (b) TsCl, Et3N, DMAP, dry CH2Cl2, 0 °C, 2 h, 89.6%; (c) LiAlH4, dry THF, 0 °C-reflux, 3 h, 84%; (d)
(i) O3, CH2Cl2, (CH3)2S, ꢀ78 °C, 6 h, (ii) Ph3P@CHCO2Et, dry THF, rt, 12 h, 86% over two steps; (e) DIBAL-H, dry CH2Cl2, ꢀ78 °C to rt, 0.5 h, 90%; (f) -(ꢀ)-DET, Ti(OiPr)4, TBHP,
D
dry CH2Cl2, ꢀ25 °C, 24 h, 90%; (g) NaN3, (MeO)3B, dry DMF, 50 °C, 3 h, 92%; (h) TsCl, Et3N, DMAP, dry CH2Cl2, 0 °C, 5 h, 64%; (i) Silica gel column chromatography; (j) LiAlH4,
dry THF, 0 °C to rt, 8 h, 68%.

4680
T. Vijai Kumar Reddy et al. / Bioorg. Med. Chem. Lett. 22 (2012) 4678–4680
14. Sabitha, G.; Yadagiri, K.; Bhikshapathi, M.; Chandrashekar, G.; Yadav, J. S.
In conclusion, the total synthesis of (2S,3R)-2-aminododecan-3-
Tetrahedron: Asymm. 2010, 21, 2524.
ol 1 was efficiently synthesized from commercially available 10-
undecenoic acid. Key steps in the developed route were Wittig
reaction and Sharpless asymmetric epoxidation to synthesize the
enantiomerically pure epoxy alcohol and regioselective epoxide
azidolysis for the synthesis of target molecule 1. The proposed
route constitutes a valuable alternative to the established method-
ologies, as the raw material comes from renewable sources and
most followed steps are operationally simple and high yielding.
The antifungal activity of the title compound 1 was found to be
comparable to miconazole towards all the tested Candida strains.
15. (a) Prabhavathi Devi, B. L. A.; Gangadhar, K. N.; Vijaya Lakshmi, K.;
Ramakrishna, S.; Madhusudan, K.; Rao, P. V.; Prasad, R. B. N.; Patent No: WO
2010/079514 A1.; (b) Kurashina, Y.; Miura, A.; Enomoto, M.; Kuwahara, S.
Tetrahedron 2011, 67, 1649; (c) Ishmuratov, G. Y.; Yakovleva, M. P.; Kharisov, R.
Y.; Botsman, O. V.; Izibarov, O. I.; Mannapov, A. G.; Tolstikov, G. A. Chem. Nat.
Compounds 2001, 37, 190.
16. (a) Fernades, R. A.; Kumar, P. Tetrahedron 2002, 58, 6685; (b) Piva, O.
Tetrahedron 1994, 50, 13687.
17. Dinda, S. K.; Das, S. K.; Panda, G. Tetrahedron 2010, 66, 9304.
18. Zhang, Z. B.; Wang, Z. M.; Wang, Y. X.; Liu, H. Q.; Lei, G. X.; Shi, M. J. Chem. Soc.,
Perkin Trans. 1 2000, 53.
19. (a) Barrett, A. G. M.; Head, J.; Smith, M. L.; Stock, N. S.; White, A. J. P.; Williams,
D. J. J. Org. Chem. 1999, 64, 6005; (b) Katsuki, T.; Sharpless, K. B. J. Am. Chem. Soc.
1980, 102, 5974.
20. Sasaki, M.; Tanino, K.; Hirai, A.; Miyashita, M. Org. Lett. 2003, 5, 1789.
21. Amsterdam, D. Susceptibility testing of antimicrobials in liquid media. In
Antibiotics in Laboratory Medicine; Loman, V., Ed., 4th Ed.; Williams and
Wilkins: Baltimore, MD, 1996; pp 52–111.
22. Assay for antifungal activity: The antifungal activity of the synthesized (2S,3R)-
2-aminododecan-3-ol was determined using well diffusion method21 against
different pathogenic Candida reference strains procured from the Microbial
Type Culture Collection (MTCC), CSIR-Institute of Microbial Technology,
Chandigarh, India. The Candida reference strains were seeded on the surface
of the media petri plates, containing Muller-Hinton agar with 0.1 mL of
previously prepared microbial suspensions individually containing 1.5 ꢁ 108
cfu mLꢀ1 (equal to 0.5 McFarland). Wells of 6.0 mm diameter were prepared in
Acknowledgements
One of the authors T.V.K. Reddy thanks the Council of Scientific
and Industrial Research (CSIR), New Delhi, India, for financial sup-
port as Junior Research Fellowship (JRF).
Supplementary data
Supplementary data (all of the full procedures and chemical
compound information) associated with this article can be found,
in the online version, at http://dx.doi.org/10.1016/j.bmcl.2012.
05.082.
the media plates using
aminododecan-3-ol at a dose range of 300–1.4
a
cork borer and the synthesized (2S,3R)-2-
l
g wellꢀ1 was added in each
well under sterile conditions in a laminar air flow chamber. Standard antibiotic
solutions of fluconazole, miconazole, nystatin and amphotericin B at a dose
range of 300–1.4 lg
wellꢀ1 and the well containing methanol served as
positive and negative controls, respectively. The plates were incubated for 24 h
at 30 °C and the well containing the least concentration showing the inhibition
zone is considered as the minimum inhibitory concentration. All experiments
were carried out in duplicates and mean values are represented.
References and notes
1. Kossuga, M. H.; Macmillan, J. B.; Rogers, E. W.; Molinski, T. F.; Nascimento, G. G.
F.; Rocha, R. M.; Berlinck, R. G. S. J. Nat. Prod. 1879, 2004, 67.
2. Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2007, 70, 461.
3. Hospenthal, D. R.; Murray, C. K.; Rinaldi, M. G. Diagn. Microbiol. Infect. Dis. 2004,
48, 153.
4. (a) Mayer, A. M. S.; Hamann, M. T. Mar. Biotechnol. 2004, 6, 37; (b) Mayer, A. M.
S.; Hamann, M. T. Comp. Biochem. Physiol. 2002, 132C, 315.
23. The spectral data of some selected compounds are given below:
Compound 8: ½a 2D8
ꢂ
+30.9 (c 1.05, CHCl3.); mp 57.0-59.0 °C; IR (KBr)
vmax: 3440,
2925, 2854, 1596, 1215, 1086 cmꢀ1
;
1H NMR (500 MHz, CDCl3) d: 0.88 (3H, t,
J = 6.9 Hz, H-12), 1.24–1.36 (12H, m, H-6, H-7, H-8, H-9, H-10, H-11), 1.40–1.47
(2H, br m, H-5), 1.52–1.59 (2H, br m, H-4), 2.83–2.85 (1H, td, J = 5.93, 1.97 Hz,
H-3), 2.88–2.92 (1H, td, J = 5.93, 1.97 Hz, H-2), 3.55–3.62 (1H, m, H-1b), 3.82–
3.89 (1H, m, H-1a); 13C NMR (75 MHz, CDCl3) d: 14.0 (CH3), 22.6 (CH2), 25.9
(CH2), 29.2 (CH2), 29.3 (CH2), 29.4 (CH2), 29.5 (CH2), 31.5 (CH2), 31.8 (CH2), 55.9
(CH), 58.3 (CH), 61.7 (CH2); m/z (EI) 169 [M-CH2OH]+.
5. Molinski, T. F. Curr. Med. Chem. Anti-Infect. Agents 2004, 3, 197.
6. Clark, R. J.; Garson, M. J.; Hooper, J. N. A. J. Nat. Prod. 2001, 64, 1568.
7. (a) Makarieva, T. N.; Denisenko, V. A.; Stonik, V. A.; Milgrom, J. M.; Rashkes, Y.
V. Tetrahedron Lett. 1989, 30, 6581; (b) Molinski, T. F.; Makarieva, T. N.; Stonik,
V. A. Angew. Chem. Int. Ed. 2000, 39, 4076; (c) Nicholas, G. M.; Hong, T. W.;
Molinski, T. F.; Lerch, M. L.; Cancilla, M. T.; Lebrilla, C. B. J. Nat. Prod. 1999, 62,
1678; (d) Nicholas, G. M.; Molinski, T. F. J. Am. Chem. Soc. 2000, 122, 4011.
8. For reviews, see: (a) Koskinen, P. M.; Koskinen, A. M. P. Synthesis 1998, 1075;
(b) Howell, A. R.; So, R. C.; Richardson, S. K. Tetrahedron 2004, 60, 11327.
9. Zaed, A. M.; Sutherland, A. Org. Biomol. Chem. 2011, 9, 8030.
10. Chen, B. S.; Yang, L. H.; Ye, J. L.; Huang, T.; Ruan, Y. P.; Fu, J.; Huang, P. Q. Eur. J.
Med. Chem. 2011, 46, 5480.
11. (a) Jiang, S.; WU, Y. L.; Yao, Z. J. Chinese J. Chem. 2002, 20, 692; (b) Sharma, A.;
Sankaranarayanan, S.; Chattopadhyay, S. J. Org. Chem. 1814, 1996, 61; (c) Lu, S.
F.; O’yang, Q. Q.; Guo, Z. W.; Yu, B.; Hui, Y. Z. J. Org. Chem. 1997, 62, 8400; (d) Lu,
S. F.; O’yang, Q. Q.; Guo, Z. W.; Yu, B.; Hui, Y. Z. Angew. Chem. Int. Ed. Engl. 1997,
36, 2344; (e) Smith, J. A.; Brzezinska, K. R.; Valenti, D. J.; Wagener, K. B.
Macromolecules 2000, 33, 3781.
Compound 11: ½a 2D8
ꢂ
+15.1 (c 0.85, CHCl3); IR (neat)
vmax: 3519, 2925, 2854,
2100, 1598, 1459, 1364, 1189, 1176, 981, 666 cmꢀ1
;
1H NMR (300 MHz, CDCl3)
d: 0.88 (3H, t, J = 6.9 Hz, H-12), 1.20–1.35 (14H, m, H-5, H-6, H-7, H-8, H-9, H-
10, H-11), 1.37–1.57 (2H, m, H-4), 2.17 (1H, br s, -OH), 2.46 (3H, s, ArCH3),
3.52–3.58 (1H, br m, H-2), 3.63–3.70 (1H, br m, H-3), 4.17 (1H, dd, J = 10.7,
7.3 Hz, H-1b), 4.31 (1H, dd, J = 10.5, 3.2 Hz, H-1a), 7.36 (2H, d, J = 8.1 Hz, ArH),
7.82 (2H, d, J = 8.3 Hz, ArH); 13C NMR (75 MHz, CDCl3) d: 14.0 (CH3), 21.6 (CH3),
22.6 (CH2), 25.4 (CH2), 29.2 (CH2), 29.3 (CH2), 29.4 (CH2), 29.6 (CH2), 31.8 (CH2),
33.2 (CH2), 64.6 (CH2), 68.9 (CH), 70.9 (CH), 127.9 (2ꢁCH), 129.9 (2ꢁCH), 132.5
(C), 145.2 (C); m/z (ESI) 420 (MNa+. C19H31N3O4NaS requires 420.1932).
Compound 1: ½a 2D9
ꢂ
+4.5 (c 0.22, CH3OH), lit.1
max: 3384, 2927, 2855, 1647, 1370,
1H NMR (300 MHz, CDCl3+CD3OD) d: 0.88 (3H,
½ ꢂ +4.6 (c 0.5, CH3OH); mp
a 2D9
106.8–109 °C, lit.9 mp 107–109 °C; IR (KBr)
v
1216, 1120, 976, 758, 666 cmꢀ1
;
t, J = 6.7 Hz, H-12), 1.19 (3H, d, J = 6.7 Hz, H-1), 1.22–1.32 (16H, m, H-4, H-5, H-
6, H-7, H-8, H-9, H-10, H-11), 3.18–3.27 (1H, br m, H-2), 3.57–3.76 (1H, br m,
H-3); 13C NMR (75 MHz, CDCl3+CD3OD) d: 11.7 (CH3),14.5 (CH3), 23.2 (CH2),
26.4 (CH2), 29.8 (CH2), 30.1 (2ꢁCH2), 30.1 (CH2), 32.4 (CH2), 33.4 (CH2), 51.8
(CH), 70.6 (CH); m/z (ESI) 202 (MH+. C12H28NO requires 202.2170).
12. (a) Nishio, T.; Niikura, K.; Matsuo, Y.; Ijiro, K. Chem. Commun. 2010, 46, 8977;
(b) Mori, K.; Harada, H.; Zagatti, P.; Cork, A.; Hall, D. R. Liebigs Ann. Chem. 1991,
259; (c) Liu, Y.; Patricelli, M. P.; Cravatt, B. F. Proc. Natl. Acd. Sci. 1999, 96, 14694.
13. Ghosal, P.; Shaw, A. K. Tetrahedron Lett. 2010, 51, 4140.