Facile enantiospecific synthesis of (+)-iso-cladospolide B

Article abstract of DOI:10.1016/j.tetasy.2010.01.011

Enantiospecific synthesis of bio-active butenolide (+)-iso-cladospolide B from d-(-)-tartaric acid in a short synthetic sequence is presented. Pivotal reaction sequence includes cross metathesis of an alkene and Wittig olefination.

Full text of DOI:10.1016/j.tetasy.2010.01.011

Tetrahedron: Asymmetry 21 (2010) 275–276
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Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Facile enantiospecific synthesis of (+)-iso-cladospolide B
*
Kavirayani R. Prasad , Vasudeva Rao Gandi
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Enantiospecific synthesis of bio-active butenolide (+)-iso-cladospolide B from
short synthetic sequence is presented. Pivotal reaction sequence includes cross metathesis of an alkene
and Wittig olefination.
D
-(À)-tartaric acid in a
Received 18 December 2009
Accepted 20 January 2010
Available online 1 March 2010
Ó 2010 Elsevier Ltd. All rights reserved.
1. Introduction
The cladospolides are a class of macrolactones isolated from the
fermented broth of cultures derived either from marine fungi or
from soil fungus. An exception to these macrolactone structures
is iso-cladospolide B 1, obtained from the ethyl acetate extract of
Cladosporium sp. isolated from the Red Sea sponge and also from
the fermentation of the marine fungal species I96S215, obtained
from a marine sponge off the Indonesian coast.1 iso-Cladospollide
B 1, is an isomer of cladospolide B 2, possessing a butenolide moi-
ety with an octyl side chain with two hydroxy groups (Fig. 1). The
corrected structure of iso-cladospolide B was established recently
by Sharma et al. by synthesis2 and was further confirmed by an-
other synthesis by Cossy et al.3a Our interest in the synthesis of
bio-active lactones from chiral pool tartaric acid culminated in
the synthesis of a variety of lactones, including macrolactone and
butenolides.4 Herein we report a concise enantiospecific approach
OH
OH
HO
O
OH
Me
O
O
O
(−)-iso-cladospolide B 1
Cladospolide B 2
OH
OH
OH
O
O
OH
OH
O
O
O
O
O
Cladospolide A 3
Cladospolide C 4
Cladospolide D 5
to the synthesis of (+)-iso-cladospolide B from
D-(À)-tartaric acid.
Figure 1. Structures of cladospolides isolated from various sources.
2. Results and discussion
corresponding silyl ether,7 which on hydrogenation afforded the pri-
mary alcohol 9 in 71% yield in two steps. Oxidation of the alcohol
with Dess–Martin periodinane (DMP) resulted in aldehyde 11,
which on Wittig olefination with the ylide Ph3P@CH–CO2Et in MeOH
yielded the Z-ester (Z/E ꢀ9:1) 10 as the major product.8 Treatment of
10 with methanolic HCl produced (+)-iso-cladospolide B 1 in 68%
yield. The spectroscopic and physical properties of 1 are in complete
agreement with those reported in the literature.2,3a
Our approach for the synthesis of (+)-iso-cladospolide B 1 is de-
picted in Scheme 1. Formation of 1 is envisaged by a Z-selective
Wittig olefination of aldehyde 11 followed by lactonization, while
the installation of the side chain is anticipated by the elaboration of
7 involving olefin cross metathesis. The synthesis of 7 is straight-
forward from 6 which is derived from tartaric acid (Scheme 2).
Accordingly, compound 7 was synthesized from 6 which is eas-
ily prepared in a few steps from D-tartaric acid as described in the
literature.5 The cross metathesis of 7 with commercially available
(R)-penten-2-ol in the presence of Grubbs second generation cata-
lyst furnished 8 in 64% yield.6 Protection of the free hydroxy group
in 7 as the TBDPS ether under standard conditions produced the
3. Conclusion
In conclusion, a short and facile synthesis of (+)-iso-cladospolide
B from D-tartaric acid is presented involving olefin cross metathesis
as the pivotal reaction. The reaction sequence depicted is concise
and is applicable for the synthesis of other cladospolides which is
currently underway in our laboratory.
* Corresponding author. Fax: +91 80 23600529.
E-mail address: prasad@orgchem.iisc.ernet.in (K.R. Prasad).
0957-4166/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2010.01.011

276
K. R. Prasad, V. R. Gandi / Tetrahedron: Asymmetry 21 (2010) 275–276
OH
OH
OTBDPS
O
H
Me
OH
Me
O
O
O
11
O
(+)-iso-cladospolide B 1
O
O
O
HO
OBn
Me
OBn
OBn
O
O
O
8
7
6
Scheme 1. Retrosynthesis for the synthesis of (+)-iso-cladospolide B 1.
OH
i) Tf2O/Et3N, CH2Cl2
O
1.5eq
O
Me
-40° C, 1h
HO
Grubbs 2nd Gen Cat
CH2Cl2, 22h, 64%
OBn
Me
OBn
MgBr
CuBr
Et2O, 2.5 h, 74%
ii)
O
O
7
6
i)TBDPSCl/Imidazole
DMAP, CH2Cl2, rt, 5h
ii) H2/Pd(OH)2/EtOAc, 12 h
71% for two steps
OH
O
OTBDPS
O
Me
OBn
OH
OH
O
O
9
8
i) DMP/CH2Cl2, 2h
ii) Ph3P=CH-CO2Et
MeOH, -78° C to -30° C
69% for two steps
OH
OTBDPS
O
HCl/MeOH
0° C to rt, 6 h
68%
OEt
Me
iso-cladospolide B 1
Me
O
O
10
O
O
Scheme 2. Synthesis of (+)-iso-cladospolide B 1.
Prasad, K. R.; Gandi, V. Tetrahedron: Asymmetry 2008, 19, 2616; (f) Prasad, K. R.;
Chandrakumar, A. J. Org. Chem. 2007, 72, 6312; (g) Prasad, K. R.; Dhaware, M. G.
Synthesis 2007, 3697; (h) Prasad, K. R.; Dhaware, M. G. Synlett 2007, 1112; (i)
Prasad, K. R.; Penchalaiah, K.; Choudhary, A.; Anbarasan, P. Tetrahedron Lett.
2007, 48, 309; (j) Prasad, K. R.; Chandrakumar, A. Tetrahedron 2007, 63, 1798; (k)
Prasad, K. R.; Anbarasan, P. Tetrahedron: Asymmetry 2006, 17, 1146; (l) Prasad, K.
R.; Anbarasan, P. Tetrahedron 2006, 62, 8303; (m) Prasad, K. R.; Anbarasan, P.
Tetrahedron: Asymmetry 2006, 17, 850; (n) Prasad, K. R.; Gholap, S. L. J. Org. Chem.
2006, 71, 3643; (o) Prasad, K. R.; Gholap, S. L. Synlett 2005, 2260; (p) Prasad, K.
R.; Anbarasan, P. Synlett 2006, 2087.
Acknowledgements
We thank the Department of Science and Technology, New Del-
hi, for funding. K.R.P. is a Swarnajayanthi fellow of the Department
of Science and Technology (DST), New Delhi. V.R.G. thanks CSIR for
a junior research fellowship.
References
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