Synthetic strategy toward the C44-C65 fragment of mirabalin

Article abstract of DOI:10.1021/ol500720j

A convergent and flexible stereoselective synthesis of one isomer of the C44-C65 fragment of mirabalin is described. The key steps include organocatalytic aldolization, ruthenium-catalyzed asymmetric hydrogenation, amide formation, Marshall stereoselectiv

Full text of DOI:10.1021/ol500720j

Letter
pubs.acs.org/OrgLett
Synthetic Strategy toward the C44−C65 Fragment of Mirabalin
Pierre-Georges Echeverria,† Sebastien Prevost,† Johan Cornil,‡ Charlene Ferard,† Sebastien Reymond,‡
́
́
̀
́
́
Amandine Guerinot,‡ Janine Cossy,*,‡ Virginie Ratovelomanana-Vidal,*,† and Phannarath Phansavath*,†
́
†PSL Research University, Chimie ParisTech - CNRS, Institut de Recherche de Chimie Paris, 75005 Paris, France
‡Laboratoire de Chimie Organique, Institute of Chemistry, Biology and Innovation (CBI) − UMR 8231 − ESPCI
ParisTech/CNRS/PSL* Research University, 10 rue Vauquelin, 75231 Paris Cedex 05, France
S
* Supporting Information
ABSTRACT: A convergent and flexible stereoselective synthesis of one isomer of the C44−C65 fragment of mirabalin is
described. The key steps include organocatalytic aldolization, ruthenium-catalyzed asymmetric hydrogenation, amide formation,
Marshall stereoselective allenylation, and the Nozaki−Hiyama−Kishi reaction.
of stereogenic centers present in the molecule and because of
solated in 2008 from the marine sponge Siliquariaspongia
1
Imirabilis, mirabalin was found to inhibit the growth of the the small amount of material available from the natural source
(1.5 mg from 6 g of the frozen sponge). Nevertheless,
prompted by the potent biological properties of the
chondropsin family, coupled with their unique structure, and
as part of our work on total synthesis of relevant
biomolecules,4,5 we decided to undertake the synthesis of a
member of this family and we focused our efforts toward the
total synthesis of one isomer of mirabalin. We report here a
convergent access to the mirabalin side chain C44−C65
wherein the unknown C46, C49, C50, C53, and C71
stereogenic centers were arbitrarily assigned to be all (R).
Accordingly, a modular route was devised in order to be able to
produce all 32 isomers of the targeted fragment C44−C65 with
respect to the five unassigned stereogenic carbon atoms
(Scheme 1).
tumor cell line HCT-116 with an IC50 value of 0.27 μM. This
compound is a new member of the chondropsin family of
macrolide lactams that currently comprises chondropsins A−D,
73-deoxychondropsin A, and poecillastrins A−C.2 Chondrop-
sins and poecillastrins are potent cancer cell growth inhibitors
that possess a 33-, 35-, or 37-membered macrolide lactam ring.
The chondropsin class of macrolide lactams has attracted the
attention of organic and medicinal chemists because of their
potent cytotoxicity due to the inhibition of vacuolar-type (H+)-
ATPase (V-ATPase), which is an emerging target for the
development of therapeutic agents.3 From a structural point of
view, mirabalin (1) exhibits a fully conjugated pentaene system
and a tetrasubstituted tetrahydropyran ring embedded in a 35-
membered lactam core. In addition, a linear polyketide side-
chain connected through an amide linkage incorporates a
unique C51−C72 moiety possessing a trisubstituted (E)-alkene
adjacent to a methylhydroxyaminohydroxy stereotetrad (Figure
1).
We envisioned a convergent approach to this fragment
involving the assembly of subunits A and B through a peptidic
Scheme 1. Retrosynthetic Strategy To Access Mirabalin Side
Chain C44−C65
The polyketide-type structure of mirabalin (1) could not be
stereochemically assigned completely due to the large number
Received: March 7, 2014
Published: April 11, 2014
Figure 1. Structure of mirabalin (1).
© 2014 American Chemical Society
2390
dx.doi.org/10.1021/ol500720j | Org. Lett. 2014, 16, 2390−2393

Organic Letters
Letter
type coupling reaction for the formation of the amide linkage
followed by a Nozaki−Hiyama−Kishi reaction with aldehyde C
to install the C50−C51 bond. Carboxylic acid A would be
obtained from isobutyraldehyde via an anti-selective organo-
catalytic aldol reaction followed by a Horner−Wadsworth−
Emmons olefination for the formation of the (E)-alkene
moiety. The preparation of subunit B would rely on a
stereoselective Marshall allenylation to install the C53−C54
bond, whereas the (E)-trisubstituted vinylsilane moiety would
be formed from the newly introduced internal alkyne through
silylcupration. The amino- and hydroxyl-bearing stereocenters
in subunits B and C, namely C55, C71, and C46, would be
controlled by ruthenium-catalyzed asymmetric hydrogenation.
Finally, the methyl-bearing stereocenter (R)-C49 would arise
from commercially available (S)-Roche ester. It is worth noting
that this versatile strategy would open access to all 32 isomers
of the mirabalin side chain since upon varying the reaction
conditions for the ruthenium-catalyzed hydrogenation and
Marshall allenylation the (R) or (S) configurations at C46, C71,
and C53 stereocenters can be easily controlled at will, whereas
starting from the (R)-Roche ester, the opposite (S)-
configuration at C49 could be obtained (Scheme 1).
We next turned our attention to the preparation of the C44−
C50 fragment C, compound 17. The synthesis started with the
alkylation of methylacetoacetate 11 with the known iodide 128
(readily obtained from (S)-Roche ester) providing the
corresponding β-keto ester 13 required for the ruthenium-
catalyzed asymmetric hydrogenation step9 (Scheme 3).
Scheme 3. Synthesis of the C44−C50 Subunit 17
The stereoselective reduction of the ketone function was
carried out using the chiral complex [Ru((R)-SYNPHOS)-
Br2]10 prepared in situ from [Ru(COD)(2-methylallyl)2]
according to the procedure disclosed in one of our
laboratories11 and delivered 14 as a single diastereomer in
excellent yield (dr > 99:1). After conversion of the newly
formed hydroxyl function into a TBS ether, deprotection of the
primary alcohol (H2, Pd/C, THF, rt) and subsequent oxidation
with Dess−Martin periodinane furnished aldehyde 17 corre-
sponding to the C44−C50 subunit (Scheme 3).
The synthesis of subunit A, compound 10, commenced with
an organocatalytic aldolization involving isobutyraldehyde and
propanal in the presence of L-proline according to the
procedure reported by MacMillan et al.6 (Scheme 2). Direct
Scheme 2. Synthesis of the C57−C65 Subunit 10
With subunits A and C in hand, we next focused on the
preparation of subunit B. The synthesis began with ruthenium-
catalyzed asymmetric hydrogenation through dynamic kinetic
resolution of the racemic α-amino-β-keto ester hydrochloride12
1812b,c (Scheme 4). The reaction was conducted in CH2Cl2/
MeOH at 50 °C under 13 bar of H2 in the presence of 1 mol %
of [[RuCl((R)-SYNPHOS)]2(μ-Cl)3]−[Me2NH2]+ complex,13
and after protection as a N-tert-butyl carbamate, the N-
protected anti-amino alcohol (2R,3R)-19 was isolated in high
diastereo- and enantioselectivities (de = 97%, ee = 98%).
Conversion of the hydroxyl into a TBS ether followed by
reduction of the ester group to the corresponding aldehyde
furnished 21, which was subjected to a Marshall reaction.14
Accordingly, addition onto 21 of a chiral allenylzinc reagent
prepared in situ by palladozincation of the (S)-propargylic
mesylate (S)-2215 delivered alcohol 23 with a good
diastereoselectivity in favor of the anti,syn,anti-isomer (dr =
87:13). The two diastereomers were separated by flash
chromatography on silica gel. At this point of the synthesis,
we needed to convert the alkynyl moiety into the
corresponding (E)-trisubstituted alkenylsilane which would be
iododesilylated at a later stage, after formation of the amide
with subunit C57−C65 A. Consequently, compound 23 was
subjected to a silylcupration16 at −78 °C in the presence of the
in situ generated bis(dimethylphenylsilyl)copper−lithium
which produced the corresponding vinylsilane 24 in 85%
yield with complete regio- and stereoselectivities (E/Z > 99:1).
Interestingly, when the reaction was carried out at 0 °C, the
related oxazolidinone 25 was obtained as the sole product in
73% yield. Iododesilylation of 25 furnished crystalline vinyl
iodide 26, the structure of which was unambiguously confirmed
by X-ray crystallographic analysis. Having in hand a properly
protection of the corresponding aldol 3 as its silyl ether 6
resulted in low yields due to the formation of side products.
Thus, we decided to reduce 3 in situ with sodium borohydride
(MeOH/DMF, 0 °C to rt) in order to obtain diol 4 which
could be readily oxidized to aldehyde 6 (Swern oxidation) after
a selective protection/deprotection sequence (TBSOTf, 2,6-
lutidine; PPTS, EtOH).7 A Barbier type addition of prenyl
bromide onto 6, in the presence of zinc dust, followed by
Dess−Martin oxidation furnished ketone 7 in 81% yield. A
Lemieux−Johnson oxidative cleavage of the olefin quantita-
tively yielded aldehyde 8, which was converted into the
corresponding α,β-unsaturated ester 9 via a Horner−Wads-
worth−Emmons olefination (E/Z > 95:5, 85% yield). Finally,
treatment of the unsaturated ester with potassium trimethylsi-
lanolate enabled the cleavage of the methyl ester, delivering the
requisite carboxylic acid 10 in 97% yield, thereby affording the
C57−C65 subunit with an overall yield of 22.8% from
isobutyraldehyde (Scheme 2).
2391
dx.doi.org/10.1021/ol500720j | Org. Lett. 2014, 16, 2390−2393

Organic Letters
Letter
Scheme 4. Synthesis of the C51−C73 Subunit 29
Scheme 5. Completion of the C44−C65 Fragment 33
NiCl2(dppe) (6 mol %). Under these conditions, alcohol 32
was obtained in 31% yield (quantitative yield based on the
recovered starting material) as a mixture of diastereomers (dr =
83:17) which were separated by flash chromatography on silica
gel.20 Finally, the fully protected C44−C65 fragment of
mirabalin, compound 33,21 was obtained after silylation of
alcohol 32 with TBSOTf under standard conditions.
In summary, we have developed a flexible strategy toward the
C44−C65 fragment of mirabalin. Our convergent and versatile
approach relies on organocatalytic aldolization, ruthenium-
catalyzed asymmetric hydrogenation, amidation, Marshall
stereoselective allenylation, and the Nozaki−Hiyama−Kishi
reaction. Most importantly, this strategy is suitable for the
preparation of all the other isomers of the C44−C65 fragment
of mirabalin. Further studies directed toward the preparation of
the macrocyclic core of mirabalin are currently investigated in
our laboratories and will be reported in due course.
ASSOCIATED CONTENT
* Supporting Information
■
S
Experimental procedures and full spectroscopic data for all new
compounds. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
protected vinyl iodide, we decided to subject 26 to a Nozaki−
Hiyama−Kishi reaction with aldehyde 17. The reaction
pleasingly afforded the corresponding alcohol 27 as a mixture
of diastereomers (dr = 54:46) in 68% yield. Unfortunately,
attempts at cleaving the oxazolidinone failed to deliver the
requisite free amine required for the amidation with carboxylic
acid 10. Nevertheless, starting from compound 24, TBS
protection of the hydroxy group and cleavage of the N-Boc
group readily afforded the targeted C51−C73 subunit 29.
With subunits C51−C73 and C57−C65 in hand, we then
examined the coupling reaction between 10 and 29 to form the
amide bond (Scheme 5). Although a variety of conditions are
available for this transformation,17 HATU, HOAt, and iPr2NEt
were used and allowed the formation of the expected amide 30
in 80% yield. Subsequent iododesilylation with N-iodosuccini-
mide (NIS) in hexafluoroisopropyl alcohol (HFIP)18 success-
fully furnished the requisite (E)-iodoalkene 31 with complete
retention of the double bond geometry. The key Nozaki−
Hiyama−Kishi reaction19 between 31 and aldehyde 17 was
then investigated. The reaction was performed in DMSO using
CrCl2 (14 equiv) in the presence of a catalytic amount of
■
*E-mail: janine.cossy@espci.fr.
*E-mail: virginie.vidal@chimie-paristech.fr.
*E-mail: phannarath.phansavath@chimie-paristech.fr.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
We thank the Agence Nationale de la Recherche (ANR
■
STIMAS, 2011−2014, P.G.E. and J.C.) and the Minister
̀
e de
l'Enseignement Super
́
ieur et de la Recherche (S.P.) for financial
support. We are grateful to Dr. M.-N. Rager (Chimie
ParisTech) for helpful NMR discussions. T. Buyck (Chimie
ParisTech) is kindly acknowledged for performing preliminary
experiments.
DEDICATION
■
This manuscript is dedicated to Prof. Max Malacria on the
occasion of his 65th birthday.
2392
dx.doi.org/10.1021/ol500720j | Org. Lett. 2014, 16, 2390−2393

Organic Letters
Letter
Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.; Gene
Champion, N.; Deschaux, G.; Dellis, P. Org. Process Res. Dev. 2003,
7, 399. (e) Genet, J.-P. Acc. Chem. Res. 2003, 36, 908.
(11) Genet, J.-P.; Pinel, C.; Ratovelomanana-Vidal, V.; Mallart, S.;
̂
t, J.-P.;
REFERENCES
■
(1) (a) Plaza, A.; Baker, H. L.; Bewley, C. A. J. Nat. Prod. 2008, 71,
473. (b) Correction: Plaza, A.; Baker, H. L.; Bewley, C. A. J. Nat. Prod.
2009, 72, 324.
(2) (a) Nishi, T.; Forgac, M. Nat. Rev. Mol. Cell. Biol. 2002, 3, 94.
(b) Bowman, E. J.; Gustafson, K. R.; Bowman, B. J.; Boyd, M. R. J.
Biol. Chem. 2003, 278, 44147.
(3) (a) Cantrell, C. L.; Gustafson, K. R.; Cecere, M. R.; Pannell, L.
K.; Boyd, M. R. J. Am. Chem. Soc. 2000, 122, 8825. (b) Rashid, M. A.;
Cantrell, C. L.; Gustafson, K. R.; Boyd, M. R. J. Nat. Prod. 2001, 64,
1341. (c) Rashid, M. A.; Gustafson, K. R.; Boyd, M. R. Tetrahedron
̂
̂
Cano de Andrade, M. C.; Laffitte, J. A. Tetrahedron: Asymmetry 1994,
̃
5, 665.
(12) (a) Makino, K.; Goto, T.; Hiroki, Y.; Hamada, Y. Angew. Chem.,
Int. Ed. 2004, 43, 882. (b) Mordant, C.; Dunkelmann, P.;
̈
Ratovelomanana-Vidal, V.; Genet
̂
, J.-P. Chem. Commun. 2004, 1296.
(c) Mordant, C.; Dunkelmann, P.; Ratovelomanana-Vidal, V.; Genet
̂
,
̈
J.-P. Eur. J. Org. Chem. 2004, 3017. For reviews on DKR, see:
(d) Noyori, R.; Tokunaga, M.; Kitamura, M. Bull. Chem. Soc. Jpn.
1995, 68, 36. (e) Ward, R. S. Tetrahedron: Asymmetry 1995, 6, 1475.
(f) Caddick, S.; Jenkins, K. Chem. Soc. Rev. 1996, 25, 447. (g) Stecher,
H.; Faber, K. Synthesis 1997, 1. (h) El Gihani, M. T.; Williams, J. M. J.
Curr. Opin. Chem. Biol. 1999, 3, 11. (i) Azerad, R.; Buisson, D. Curr.
Lett. 2001, 42, 1623. (d) Chevallier, C.; Laprev
́
ote, O.; Bignon, J.;
Debitus, C.; Guenard, D.; Sevenet, T. Nat. Prod. Res. 2004, 18, 479.
́
́
(e) Rashid, M. A.; Gustafson, K. R.; Crouch, R. C.; Groweiss, A.;
Pannell, L. K.; Van, Q. N.; Boyd, M. R. Org. Lett. 2002, 4, 3293.
(f) Takada, K.; Choi, B. W.; Rashid, M. A.; Gamble, W. R.; Cardellina,
J. H.; Van, Q. N.; Lloyd, J. R.; McMahon, J. B.; Gustafson, K. R. J. Nat.
Opin. Chem. Biol. 2000, 11, 565. (j) Ratovelomanana-Vidal, V.; Genet
̂
,
J.-P. Can. J. Chem. 2000, 78, 846. (k) Huerta, F. F.; Minidis, A. B. E.;
Prod. 2007, 70, 428. (g) Per
Barros-Angueira, F.; Rey, J. M.; García-García, A. Cancer Treat. Rev.
2009, 35, 707. (h) Parks, S. K.; Chiche, J.; Pouyssegur, J. Nature Rev.
Cancer 2013, 13, 611.
(4) (a) Prevost, S.; Ayad, T.; Phansavath, P.; Ratovelomanana-Vidal,
V. Adv. Synth. Catal. 2011, 353, 3213. (b) Prevost, S.; Phansavath, P.;
́ ́
ez-Sayans, M.; Somoza-Martin, J. M.;
Backvall, J.-E. Chem. Soc. Rev. 2001, 30, 321. (l) Kim, M. J.; Ahn, Y.;
̈
Park, J. Curr. Opin. Biotechnol. 2002, 13, 578. (m) Pellissier, H.
Tetrahedron 2003, 59, 8291. (n) Vedejs, E.; Jure, M. Angew. Chem., Int.
́
Ed. 2005, 44, 3974. (o) Fogassy, E.; Nog
́ ́
radi, M.; Kozma, D.; Egri, G.;
́
Palovics, E.; Kiss, V. Org. Biomol. Chem. 2006, 4, 3011. (p) Martín-
́
́
Matute, B.; Backvall, J. E. Curr. Opin. Chem. Biol. 2007, 11, 226.
̈
Haddad, M. Tetrahedron: Asymmetry 2010, 21, 16. (c) Tone, H.;
Buchotte, M.; Mordant, C.; Guittet, E.; Ayad, T.; Ratovelomanana-
Vidal, V. Org. Lett. 2009, 11, 1995. (d) Roche, C.; Le Roux, R.;
Haddad, M.; Phansavath, P.; Genet
C.; Desroy, N.; Haddad, M.; Phansavath, P.; Genet
2008, 10, 3911. (f) Blanc, D.; Madec, J.; Popowyck, F.; Ayad, T.;
Phansavath, P.; Ratovelomanana-Vidal, V.; Genet, J.-P. Adv. Synth.
Catal. 2007, 349, 1592. (g) Mordant, C.; Reymond, S.; Tone, H.;
Lavergne, D.; Touati, R.; Ben Hassine, B.; Ratovelomanana-Vidal, V.;
̂
Genet, J.-P. Tetrahedron 2007, 63, 6115.
(5) For selected examples, see: (a) Bensoussan, C.; Rival, N.;
Hanquet, G.; Colobert, F.; Reymond, S.; Cossy, J. Tetrahedron 2013,
69, 7759. (b) Gallon, J.; Esteban, J.; Bouzbouz, S.; Campbell, M.;
Reymond, S.; Cossy, J. Chem.Eur. J. 2012, 18, 11788.
(c) Commandeur, M.; Commandeur, C.; Cossy, J. Pure Appl. Chem.
2012, 84, 1567. (d) Commandeur, M.; Commandeur, C.; Cossy, J.
Org. Lett. 2011, 13, 6018. (e) ElMarrouni, A.; Joolakanti, S. R.; Colon,
A.; Heras, M.; Arseniyadis, S.; Cossy, J. Org. Lett. 2010, 12, 4074.
(f) Druais, V.; Hall, M. J.; Corsi, C.; Wendeborn, S. V.; Meyer, C.;
(q) Pellissier, H. Tetrahedron 2008, 64, 1563. (r) Pellissier, H. Adv.
Synth. Catal. 2011, 353, 659.
(13) (a) Ikariya, T.; Ishii, Y.; Kawano, H.; Arai, T.; Saburi, M.;
Yoshikawa, S.; Akutagawa, S. J. Chem. Soc., Chem. Commun. 1985, 922.
(b) Ohta, T.; Tonomura, Y.; Nozaki, K.; Takaya, H.; Mashima, K.
Organometallics 1996, 15, 1521. (c) Mashima, K.; Nakamura, T.;
Matsuo, Y.; Tani, K. J. Organomet. Chem. 2000, 607, 51. Jeulin, S.;
̂
, J.-P. Synlett 2009, 573. (e) Roche,
̂
, J.-P. Org. Lett.
̂
Champion, N.; Dellis, P.; Ratovelomanana-Vidal, V.; Genet
̂
, J.-P.
Synthesis 2005, 3666.
(14) (a) Marshall, J. A.; Adams, N. D. J. Org. Chem. 1998, 63, 3812.
(b) Marshall, J. A.; Mulhearn, J. J. Org. Lett. 2005, 7, 1593.
(15) (a) Marshall, J. A.; Wang, X. J. Org. Chem. 1992, 57, 1242.
(b) Coleman, R. S.; Lu, X.; Modolo, I. J. Am. Chem. Soc. 2007, 129,
3826.
(16) (a) Fleming, I.; Newton, T. W.; Roessier, F. J. Chem. Soc., Perkin
Trans. 1 1981, 2527. (b) Fleming, I.; Roberts, R. S.; Smith, S. C. J.
Chem. Soc., Perkin Trans. 1 1998, 1209. (c) Herrmann, A. T.; Martinez,
S. R.; Zakarian, A. Org. Lett. 2011, 13, 3636.
(17) El-Faham, A.; Albericio, F. Chem. Rev. 2011, 111, 6557.
(18) Ilardi, E. A.; Stivala, C. E.; Zakarian, A. Org. Lett. 2008, 10, 1727.
(19) (a) Takai, K.; Tagashira, M.; Kuroda, T.; Oshima, K.; Utimoto,
K.; Nozaki, H. J. Am. Chem. Soc. 1986, 108, 6048. (b) Harnying, W.;
Kaiser, A.; Klein, A.; Berkessel, A. Chem.Eur. J. 2011, 17, 4765.
(20) The configuration at C50 of compound 32 (major
diastereomer) was assigned by NOESY experiments; see the
Supporting Information.
Cossy, J. Tetrahedron 2010, 66, 6358. (g) Guer
́
inot, A.; Lepesqueux,
G.; Sable, S.; Reymond, S.; Cossy, J. J. Org. Chem. 2010, 75, 5151.
́
(h) Amans, D.; Bareille, L.; Bellosta, V.; Cossy, J. J. Org. Chem. 2009,
74, 7665. (i) Mandel, A. L.; Bellosta, V.; Curran, D. P.; Cossy, J. Org.
Lett. 2009, 11, 3282. (j) Amans, D.; Bellosta, V.; Cossy, J. Chem.Eur.
J. 2009, 15, 3457. (k) Bressy, C.; Vors, J.-P.; Hillebrand, S.;
Arseniyadis, S.; Cossy, J. Angew. Chem., Int. Ed. 2008, 47, 10137.
(l) Reymond, S.; Cossy, J. Eur. J. Org. Chem. 2006, 4800.
(6) Northrup, A. B.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002,
124, 6798.
(21) Comparison of the NMR spectra of fragment 33 with the
natural product 1 did not allow us to deduce the correct configuration
on the natural product.
(7) Aldehydes 3 and 6 were not isolated and were directly involved in
the following step.
(8) Keck, G. E.; Palani, A.; McHardy, S. F. J. Org. Chem. 1994, 59,
3113.
(9) For reviews on Ru-catalyzed asymmetric hydrogenation, see:
(a) Ohkuma, T.; Kitamura, M.; Noyori, R. Asymmetric Hydro-
genation. In Catalytic Asymmetric Synthesis, 2nd ed.; Ojima, I., Ed.;
Wiley-VCH: New York, 2000; pp 1−110. (b) Kitamura, M.; Noyori,
R. Hydrogenation and Transfer Hydrogenation. In Ruthenium in
Organic Synthesis; Murahashi, S.-i., Ed.; Wiley-VCH: Weinheim, 2004;
pp 3−52.
(10) (a) Duprat de Paule, S.; Champion, N.; Ratovelomanana-Vidal,
V.; Genet
de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.; Genet
Champion, N.; Dellis, P. Tetrahedron Lett. 2003, 44, 823. (c) Duprat
de Paule, S.; Jeulin, S.; Ratovelomanana-Vidal, V.; Genet, J.-P.;
Champion, N.; Dellis, P. Eur. J. Org. Chem. 2003, 1931. (d) Duprat de
̂
, J.-P.; Dellis, P. French Patent 2,830,254, 2001. (b) Duprat
̂
, J.-P.;
̂
2393
dx.doi.org/10.1021/ol500720j | Org. Lett. 2014, 16, 2390−2393