Efficient total synthesis of iso-cladospolide B and cladospolide B

Article abstract of DOI:10.1016/j.tetlet.2005.07.153

An efficient synthesis of iso-cladospolide B and cladospolide B has been achieved using Jacobsen's hydrolytic kinetic resolution (HKR), Sharpless asymmetric dihydroxylation and Yamaguchi macrolactonization as the key steps.

Full text of DOI:10.1016/j.tetlet.2005.07.153

Tetrahedron
Letters
Tetrahedron Letters 46 (2005) 6625–6627
Efficient total synthesis of iso-cladospolide B and cladospolide B
Satyendra Kumar Pandey and Pradeep Kumar*
Division of Organic Chemistry: Technology, National Chemical Laboratory, Homi Bhabha Road, Pune 411008, India
Received 22 June 2005; revised 21 July 2005; accepted 29 July 2005
Available online 15 August 2005
Abstract—An efficient synthesis of iso-cladospolide B and cladospolide B has been achieved using JacobsenÕs hydrolytic kinetic
resolution (HKR), Sharpless asymmetric dihydroxylation and Yamaguchi macrolactonization as the key steps.
Ó 2005 Elsevier Ltd. All rights reserved.
The novel hexaketide compounds iso-cladospolide B 1
and cladospolide B 2 were isolated from the fungal iso-
late I96S215.1 Cladospolide A 3, cladospolide B 2 along
with cladospolide C 4 were also isolated from the soil
fungi Cladosporium tenuissimum, whose culture filtrate
showed plant growth retardant activity towards rice
seedlings. Cladospolide B 2 is inhibitory to shoot elon-
gation of rice seedlings (Oryza sativa L.) without damag-
ing the cells.2 Recently, cladospolide D 5 isolated
from Cladosporium sp. FT-0012 whose configuration
remains to be fully determined, was shown to exhibit
antimicrobial activity against Mucor racemosus and
Pyricularia oryzae with IC50 values of 0.15 and 29
lg mlꢀ1, respectively3 (Fig. 1). The absolute configura-
tion of the three stereogenic centres (4S,5S and 11R) of
iso-cladospolide B 1 was determined by Figadere and
co-workers who also accomplished its synthesis for the
first time.4 Very recently, Banwell and co-workers
reported the first total synthesis of cladospolide B using
a chemoenzymatic 16-step synthesis via a ring-closing
metathesis and photorearrangement of an E isomer.5
OH
OH
O
O
OH
O
1
O
2
OH
iso-cladospolide B
cladospolide B
R1
R2
OH
OH
O
O
O
O
R2 =OH
R1 =H,
R1 =OH, R2 =H
5
O
cladospolide A
cladospolide C
3
4
cladospolide D
Figure 1.
H
H
N
O
N
O
Co
t-Bu
As part of our research programme aimed at developing
enantioselective syntheses of naturally occurring lac-
tones6 and amino alcohols,7 we have accomplished the
total synthesis of iso-cladospolide B 1 and cladospolide
B 2 from commercially available propylene oxide
employing JacobsenÕs HKR, a Sharpless asymmetric
t-Bu
OAc
t-Bu
t-Bu
(R,R)-SalenCo(III) OAc complex
Figure 2.
dihydroxylation and Yamaguchi macrolactonization as
the key steps.
Keywords: Cladospolide B; iso-Cladospolide B; Sharpless asymmetric
dihydroxylation; Hydrolytic kinetic resolution; Yamaguchi macro-
lactonization.
Propylene oxide 6 was subjected to JacobsenÕs HKR
using (R,R)-Salen-Co-(OAc) catalyst (Fig. 2) to give
25
R-propylene oxide 6a as a single isomer ½aꢁD +11.7
25
*
Corresponding author. Tel.: +91 20 25902050; fax: +91 20
25893614; e-mail: pk.tripathi@ncl.res.in
(neat) {lit.8 for (S)-propylene oxide ½aꢁD ꢀ11.6 (neat)},
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.07.153

6626
S. K. Pandey, P. Kumar / Tetrahedron Letters 46 (2005) 6625–6627
and concomitant cyclization of the olefin 14 was
achieved in one-pot using 3% methanolic HCl to furnish
OH
O
O
(i)
OH
+
the target molecule, iso-cladospolide B 1 in 77% yield;
25
25
6a
6b
½aꢁD ꢀ105.3 (c 0.23, MeOH) {lit.4 ½aꢁD ꢀ105.0 (c 0.23,
MeOH)}. The physical and spectroscopic data were in
full agreement with the literature.1
6
Scheme 1. Reagents and conditions: (i) R,R-Salen-Co-(OAc)
(0.5 mol %), distd H2O (0.55 equiv), 0 °C, 14 h, (46% for 6a, 45% for
6b).
The synthesis of cladospolide B 2 started from the olefin
14 as illustrated in Scheme 3. Ester hydrolysis of 14 with
LiOH followed by TPS deprotection using TBAF led to
the seco-acid 15 in 88% yield. Macrolactonization of 15
under Yamaguchi conditions13 provided lactone 16 in
excellent yield, which on subsequent cleavage of the ace-
tonide afforded the target molecule 2 in 88% yield;
which was easily isolated from the more polar diol 6b by
distillation (Scheme 1).
With enantiomerically pure propylene oxide 6a in hand,
we then subjected it to copper-catalyzed (CuI) regiosel-
ective opening with the Grignard reagent, derived from
benzyl protected bromopentanol to furnish alcohol 7 in
77% yield (Scheme 2). Hydroxyl protection of 7 with
tert-butyldiphenylsilyl chloride and imidazole in the
presence of a catalytic amount of DMAP afforded the
silyl ether 8 in 95% yield which on debenzylation using
H2–Pd/C furnished the alcohol 9 in 91% yield. Com-
pound 9 was then oxidized to the corresponding alde-
hyde by Swern oxidation9 and subsequently treated
with (ethoxycarbonylmethylene)triphenylphosphorane
in dry THF to furnish the Wittig product 10 in 92%
yield. The olefin 10 was treated with osmium tetroxide
and potassium ferricyanide as co-oxidant in the presence
of (DHQ)2PHAL under Sharpless asymmetric condi-
tions10 to give the diol 11 in 94% yield with 96% de.11
Treatment of diol 11 with 2,2-dimethoxypropane in
the presence of a catalytic amount of p-TSA gave com-
pound 12, which on subsequent reduction using LiAlH4
provided the alcohol 13 in excellent yield. The alcohol
was oxidized to the aldehyde under Swern conditions
and subsequently treated with (ethoxycarbonylmethyl-
ene)triphenylphosphorane in dry methanol at ꢀ78 °C
for 24 h to give the Wittig product 1412 in 82% yield with
a Z:E ratio of 85:15,12 the isomers of which could easily
be separated by silica gel column chromatography.
Finally, deprotection of the acetonide and TPS groups
25
25
½aꢁD ꢀ164.3 (c 0.10, MeOH), {lit.5 ½aꢁD ꢀ162.0 (c 0.10,
MeOH)}. The physical and spectroscopic data were in
full agreement with the literature.5
In conclusion, a practical and enantioselective synthesis
of iso-cladospolide B and cladospolide B has been
achieved employing JacobsenÕs HKR, a Sharpless asym-
metric dihydroxylation and Yamaguchi macrolactoniza-
tion as the key steps. The merits of this synthesis are
O
OH
a
OH
14
15
O
O
O
O
O
O
c
b
O
OH
16
2
O
OH
Scheme 3. Reagents and conditions: (a) (i) LiOH, MeOH/H2O (3:2),
0 °C to rt; (ii) TBAF, CH2Cl2, 0 °C to rt, 88%, two steps; (b) 2,4,6-
trichlorobenzoyl chloride, Et3N, THF, then DMAP, benzene, 86%; (c)
CF3COOH, THF/H2O, 0 °C, 1 h, 88%.
OH
OTPS
OTPS
O
d
c
b
a
OBn
OBn
OH
6a
7
8
9
O
OTPS
O
OTPS
OH
O
O
OTPS
f
e
OEt
OH
OEt
OEt
11
12
O
OH
10
OTPS
O
OTPS
O
OH
h
i
g
OEt
OH
14
O
1
O
O
13
O
O
Scheme 2. Reagents and conditions: (a) C6H5CH2O(CH2)5MgBr, CuI, THF, ꢀ78 °C, 12 h, 77%; (b) TBDPSCl, imidazole, DMAP, DMF, 0 °C, 2 h,
95%; (c) H2–Pd/C, EtOAc, rt, 91%; (d) (i) (COCl)2, DMSO, CH2Cl2, ꢀ78 °C, Et3N, ꢀ65 °C, 1 h; (ii) Ph3P@CHCO2Et, THF, reflux, 6 h, 92%; (e)
(DHQ)2PHAL (1 mol %), 0.1 M OsO4 (0.4 mol %), K2CO3, K3Fe(CN)6, MeSO2NH2, t-BuOH/H2O 1:1, 0 °C, 24 h, 94%; (f) 2,2-DMP, p-TSA (cat.)
CH2Cl2, 2 h, 89%; (g) LiAlH4, THF, 0 °C to rt, 3 h, 85%; (h) (i) (COCl)2, DMSO, CH2Cl2, ꢀ78 °C, Et3N, ꢀ65 °C, 1 h; (ii) Ph3P@CHCO2Et, MeOH,
ꢀ78 °C, 24 h, 82%; (i) 3% MeOH/HCl, 0 °C to rt, 5 h, 77%.

S. K. Pandey, P. Kumar / Tetrahedron Letters 46 (2005) 6625–6627
6627
R. A.; Kumar, P. Tetrahedron Lett. 2000, 41, 10309–
10312; (d) Naidu, S. V.; Kumar, P. Tetrahedron Lett. 2003,
44, 1035–1037; (e) Gupta, P.; Fernandes, R. A.; Kumar, P.
Tetrahedron Lett. 2003, 44, 4231–4232; (f) Kondekar, N.
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363.
high enantio- and diastereoselectivity with high yielding
reaction steps. The synthetic strategy described has sig-
nificant potential for further extension to other stereo-
isomers and analogues of iso-cladospolide B and
cladospolide B.
Acknowledgements
8. Schaus, S. E.; Brandes, B. D.; Larrow, J. F.; Tokunaga,
M.; Hansen, K. B.; Gould, A. E.; Furrow, M. E.;
Jacobsen, E. N. J. Am. Chem. Soc. 2002, 124, 1307–1315.
9. For reviews on the Swern oxidation, see: (a) Tidwell, T. T.
Synthesis 1990, 857–870; (b) Tidwell, T. T. Org. React.
1990, 39, 297–572.
S.K.P. thanks CSIR New Delhi for a research fellow-
ship. We are grateful to Dr. M. K. Gurjar for his sup-
port and encouragement. Financial support from the
DST, New Delhi (Project Grant No. SR/S1/OC-40/
2003) is gratefully acknowledged. This is NCL commu-
nication No. 6685.
10. (a) Becker, H.; Sharpless, K. B. Angew Chem., Int. Ed.
Engl. 1996, 35, 448–451; (b) Kolb, H. C.; VanNieuwenhze,
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(c) Torri, S.; Liu, P.; Bhuvaneswari, N.; Amatore, C.;
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11. The diastereoselectivity was determined from 13C NMR
spectral data. Spectral data of compound 11: colorless oil,
25
½aꢁD +6.68 (c 1.0, CHCl3); IR (neat): mmax 3410, 2932,
1
1713, 1653, 1609, 1590, 1216 cmꢀ1; H NMR (200 MHz,
CDCl3): d 1.06 (s, 9H), 1.07 (t, J = 5.9 Hz, 3H), 1.18–1.58
(m, 13H), 2.10 (br s, 2H), 3.76–3.90 (m, 2H), 4.06 (d,
J = 2.0 Hz, 1H), 4.30 (q, J = 7.2 Hz, 2H), 7.32–7.47 (m,
6H), 7.66–7.71 (m, 4H); 13C NMR (50 MHz, CDCl3): d
14.1, 19.2, 23.2, 25.1, 25.6, 27.0, 29.4, 33.6, 39.2, 61.9, 69.4,
72.5, 73.1, 127.3, 129.3, 134.5, 134.8, 135.8, 173.7. Anal.
Calcd for C28H42O5Si (486.72): C, 69.10; H, 8.70. Found:
C, 69.04; H, 8.73.
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12. The Z:E ratio of compound 14 was determined from the
1H NMR spectrum. Spectral data of compound 14:
25
½aꢁD +29.22 (c 1.0, CHCl3); IR (neat): mmax 3071, 2932,
1
1723, 1655, 1589, 1462, 1378, 1191; H NMR (200 MHz,
CDCl3): d 1.05 (s, 9H), 1.14–1.37 (m, 12H), 1.44 (s, 6H),
1.51–1.65 (m, 4H), 3.64–3.90 (m, 2H), 4.18 (q, J = 7.1 Hz,
2H), 5.27 (t, J = 8.6 Hz, 1H), 5.93 (d, J = 11.8 Hz, 1H),
6.13 (dd, J = 11.7, 8.7 Hz, 1H), 7.32–7.46 (m, 6H), 7.66–
7.70 (m, 4H); 13C NMR (50 MHz, CDCl3): d 14.1, 19.2,
23.1, 25.0, 26.0, 27.0, 29.6, 31.9, 39.3, 60.3, 69.4, 76.0, 80.9,
109.1, 122.9, 127.3, 129.3, 134.5, 134.8, 135.8, 145.5, 165.3.
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Found: C, 71.66; H, 8.74.
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