Stereoselective synthesis of basiliskamides A and B via Prins cyclisation

Article abstract of DOI:10.1016/j.tetlet.2008.07.024

A stereoselective and convergent approach to basiliskamides A and B is achieved through our recently developed strategy for the construction of polyketide precursors via Prins cyclisation. The approach mainly relies upon reductive opening of 1-iodomethyl cyclic ethers, Mitsunobu inversion, Takai olefination and Stille coupling along with Prins cyclisation.

Full text of DOI:10.1016/j.tetlet.2008.07.024

Tetrahedron Letters 49 (2008) 5427–5430
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Stereoselective synthesis of basiliskamides A and B via Prins cyclisation
*
J. S. Yadav , P. Purushothama Rao, M. Sridhar Reddy, A. R. Prasad
Division of Organic Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A stereoselective and convergent approach to basiliskamides A and B is achieved through our recently
developed strategy for the construction of polyketide precursors via Prins cyclisation. The approach
mainly relies upon reductive opening of 1-iodomethyl cyclic ethers, Mitsunobu inversion, Takai olefin-
ation and Stille coupling along with Prins cyclisation.
Received 23 May 2008
Revised 30 June 2008
Accepted 3 July 2008
Available online 6 July 2008
Ó 2008 Elsevier Ltd. All rights reserved.
Keywords:
Natural products
Prins cyclisation
Reductive cleavage
Mitsunobu inversion and Stille coupling
Basiliskamides A (6) and B (7) were co-isolated by Andersen and
co-workers in 2002 from the marine bacterium PNG-276 found off
the coast of Papua New Guinea.1 Initial biological studies showed
that both basiliskamides A and B showed antifungal activity
against Candida albicans and Aspergillus fumigatus. Basiliskamides
A and B are structurally identical in every respect except for the po-
sition of the cinnamate ester: C9 in basiliskamide A and C7 in bas-
iliskamide B. The same authors elucidated the structures after
rigorous analysis of spectral and comparative data. Recently, Panek
and co-workers realised a synthesis via asymmetric crotyl bora-
tions thereby providing an absolute proof for the stereostructures
of the natural products.2a Very recently, during the completion of
our synthesis, another synthesis of basiliskamide B was reported
by Dias et al.2b Inspired by the biological properties and structural
similarity to other biologically active natural products, such as cro-
cacins (1, 2 and 3), pironetin (4) and YM-47522 (5), we investi-
105 in the presence of TFA4 resulted in the trifluoroacetate salt of
8, which on treatment with K2CO3 in MeOH gave tetrahydropyran
diol 8 as the only isolable diastereomer in 50% yield. Though the
stereochemical aspects of such Prins cyclisations and structurally
similar compounds of 8 have been discussed in detail previously,3,4
we sought to analyse the products (see later) in this case. Protec-
tion of 8 gave TBS ether 11, and inversion of the secondary hydro-
xyl group using Mitsunobu’s protocol6 produced pyranol 12 in 68%
overall yield. Protection of the inverted alcohol as its TIPS ether and
deprotection of the TBS group resulted in pyranyl methanol 13 in
87% yield over two steps. The hydroxyl group in 13 was iodinated
using Ph3P, imidazole and iodine to give 14, which on reductive
ring-opening using Zn in EtOH furnished homoallylic alcohol 15
in 87% yield (2 steps).4b,h Esterification of the resulting alcohol with
trans-cinnamic acid using DCC and DMAP afforded 16 in 90% yield.
The terminal olefin group in 16 was selectively subjected to
gated the synthesis of basiliskamides
A
and
B
via Prins
dihydroxylation7 using AD-mix-
a, followed by oxidative cleavage
cyclisation.3 As part of our successful efforts towards the total syn-
thesis of such natural products via Prins cyclisation,4 we have
accomplished a stereoselective total synthesis of the basiliska-
mides via Prins cyclisation and reductive ring-opening sequence.
In our retrosynthetic analysis (Fig. 1), we envisaged that the
core part of the basiliskamides could be easily derived from pyra-
nyl methanol 8 via a Mitsunobu inversion. Pyranyl methanol 8
could be easily constructed via Prins cyclisation, in analogy to
our previous approach, from known reagents 9 and 10.4
of the resulting diol to reveal the corresponding aldehyde, treat-
ment of which with CrCl2 and CHI3 gave trans-vinyl iodide 17 in
60% yield over the three steps.8 The remaining formal Stille cou-
pling2 of 17 with 18 using PdCl2(CH3CN)2 produced 19, which on
cleavage of the TIPS ether with HF in pyridine furnished the natural
product basiliskamide A 6 in 60% yield over the two steps. The syn-
thetic compound showed spectral and analytical data (1H NMR, 13
NMR, IR, Rf and [
]D) identical with that of the natural sample.1,9
C
a
The synthesis of the next target, basiliskamide B 7, is described
in Scheme 2. Although the structures of basiliskamides A and B are
only differentiated by the position of the cinnamoyl moiety, it was
necessary to start from intermediate 8 to effect an efficient synthe-
sis of 7. Thus, the 1° hydroxyl group in Prins cyclisation product 8
was protected as the corresponding tosylate using tosyl chloride in
Our synthesis of basiliskamide A is outlined in Scheme 1. Prins
cyclisation between known homoallylic alcohol 94c and aldehyde
* Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160512.
E-mail address: yadavpub@iict.res.in (J. S. Yadav).
0040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.07.024

5428
J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 5427–5430
Me Me
OR
NH
O
N
H
O
OMe OMe
Me
O
R = Me, crocacin A (1)
R = H, crocacin B (2)
Me
O
OMe OH
O
Me Me
NH2
Me Me
Et
OMe OMe
Me
O
(+)-crocacin C (3)
Pironetin (4)
O
O
Ph
O
OH
OH
O
Ph
H2N
H2N
R
O
O
R = Et, YM-47522 (5)
R = Me, basiliskamide A (6)
basiliskamide B (7)
OH
HO
Prins
Cyclisation
9
OH
+
HO
O
8
O
10
Figure 1.
OH
OH
O
HO
c
10
d, e
9
RO
OH
RO
a
O
O
12
8, R = H
11, R = TBS
b
OTIPS
OTIPS
O
OTIPSOH
g
h
f
I
HO
O
15
14
13
O
O
OTIPSO
Ph
OTIPSO
Ph
i, j
k
I
16
H2N
O
17
SnBu3
18
O
OTIPSO
Ph
l
H2N
Basiliskamide A
19
O
Scheme 1. Reagents and conditions: (a) TFA, CH2Cl2, 0 °C to rt, 3 h then K2CO3, MeOH, rt, 30 min, 50%; (b) TBDMSCl, imidazole, CH2Cl2, 0 °C to rt, 3 h, 85%; (c) DEAD, p-
nitrobenzoic acid, Ph3P, THF, 0 °C to rt, 30 min, then K2CO3, MeOH, rt, 30 min, 80%; (d) TIPS(OTf)2, 2,6-lutidine, 0 °C to rt, 6 h, 95%; (e) CSA, MeOH, CH2Cl2 (7:1), 0 °C to rt,
10 min, 92%; (f) Ph3P, imidazole, I2, benzene, 0 °C to rt, 2 h, 95%; (g) Zn, EtOH, NaHCO3, reflux, 2 h, 92%; (h) trans-cinnamic acid, DCC, DMAP, CH2Cl2, 0 °C to rt, 6 h, 90%; (i) (i)
AD-mix-a
, CH3SO2NH2, tBuOH: H2O (1:1), 24 h; (ii) NaIO4, THF/H2O (2:1), 2 h; (j) CrCl2, CHI3, dioxane/THF (6:1), 12 h, 60% (3 steps); (k) PdCl2(CH3CN)2, DMF, rt, 36 h; (l) HF–
Py, THF, rt, 12 h, 60% (2 steps).
triethylamine to give 20 in 90% yield. We observed that the 1H
NMR specturm of this compound showed clear signals due to H-
2 (d 2.90, dd, 1H, J = 9.8, 1.5 Hz), H-4 (d 3.32, ddd, J = 12.0, 4.5,
2.2 Hz) and H-5 (d 1.94, ddd, 1H, J = 13.5, 9.8, 4.5 Hz) with coupling
constants consistent with the equatorial disposition of all the sub-
stituents on the ring. The 2° hydroxyl group in 20 was inverted

J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 5427–5430
5429
O
O
OH
O
Ph
O
Ph
c
a
b
d
8
TsO
O
I
TsO
O
20
O
O
21
22
O
O
Ph
O
Ph
O
OMOM
OH
Ph
I
O
OMOM
f, g
e
24
23
25
O
Ph
I
O
OH
k
h
Basiliskamide B
H2N
SnBu3
26
18
O
Scheme 2. Reagents and conditions: (a) TsCl, TEA, CH2Cl2, 0 °C to rt, 6 h, 90%; (b) DEAD, trans-cinnamic acid, Ph3P, THF, 0 °C to rt, 2 h, 75%; (c) NaI, acetone, reflux, 24 h, 92%;
t
(d) Zn, EtOH, NaHCO3, reflux, 4 h, 85%; (e) MOMCl, DIPEA, DMAP, CH2Cl2, 0 °C to rt, 6 h, 95%; (f) (i) AD-mix-
a, CH3SO2NH2, BuOH/H2O (1:1), 24 h, 80%; (ii) NaIO4, THF/H2O
(2:1), rt, 2 h, 95%; (g) CrCl2, CHI3, dioxane/THF (6:1), 12 h, 83%; (h) BCl3, CH2Cl2, ꢀ78 °C, 4 h; (k) PdCl2(CH3CN)2, DMF, rt, 24 h, 52% (2 steps).
12217; (f) Crosby, S. R.; Harding, J. R.; King, C. D.; Parker, G. D.; Willis, C. L. Org.
with trans-cinnamic acid, DEAD and Ph3P to give the cinnamic es-
ter 21 with the required configuration. Next, the tosyl group in 21
was replaced by iodide in the presence of NaI in acetone to yield
22, which on subsequent reductive elimination using Zn in EtOH
gave homoallylic alcohol 23 in 58% yield over 3 steps.4b,h Protection
of the resulting alcohol as its MOM ether using MOMCl, DIPEA and
DMAP gave 24. Selective hydrolysis of the terminal olefin bond fol-
lowed by oxidative cleavage produced the corresponding aldehyde,
which on iodo olefination gave trans olefin 25 in 72% overall yield.
Cleavage of the MOM ether in 25 was achieved using BCl3 in CH2Cl2
at ꢀ78 °C, and the resulting hydroxy iodo olefin 26 underwent
Stille coupling with 18 smoothly to furnish basiliskamide B 7 in
52% yield over the two steps. The synthetic sample was identical
Lett. 2002, 4, 3407–3410; (g) Marumoto, S.; Jaber, J. J.; Vitale, J. P.; Rychnovsky, S.
D. Org. Lett. 2002, 4, 3919–3922; (h) Kozmin, S. A. Org. Lett. 2001, 3, 755–758; (i)
Jaber, J. J.; Mitsui, K.; Rychnovsky, S. D. J. Org. Chem. 2001, 66, 4679–4686; (j)
Kopecky, D. J.; Rychnovsky, S. D. J. Am. Chem. Soc. 2001, 123, 8420–8422; (k)
Rychnovsky, S. D.; Thomas, C. R. Org. Lett. 2000, 2, 1217–1219; (l) Rychnovsky, S.
D.; Yang, G.; Hu, Y.; Khire, U. R. J. Org. Chem. 1997, 62, 3022–3023; (m) Su, Q.;
Panek, J. S. J. Am. Chem. Soc. 2004, 126, 2425–2430; (n) Yadav, J. S.; Reddy, B. V.
S.; Sekhar, K. C.; Gunasekar, D. Synthesis 2001, 6, 885–888; (o) Yadav, J. S.; Reddy,
B. V. S.; Reddy, M. S.; Niranjan, N. J. Mol. Catal. A: Chem. 2004, 210, 99–103; (p)
Yadav, J. S.; Reddy, B. V. S.; Reddy, M. S.; Niranjan, N.; Prasad, A. R. Eur. J. Org.
Chem. 2003, 1779–1783.
4. (a) Yadav, J. S.; Reddy, M. S.; Rao, P. P.; Prasad, A. R. Tetrahedron Lett. 2006, 47,
4397–4401; (b) Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2006, 47,
4937–4941; (c) Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2005, 46,
2133–2136; (d) Yadav, J. S.; Reddy, M. S.; Prasad, A. R. Tetrahedron Lett. 2006, 47,
4995–4998; (e) Yadav, J. S.; Reddy, M. S.; Rao, P. P.; Prasad, A. R. Synlett 2007, 13,
2049–2052; (f) Yadav, J. S.; Rao, P. P.; Reddy, M. S.; Rao, N. V.; Prasad, A. R.
Tetrahedron Lett. 2007, 48, 1469–1471; (g) Yadav, J. S.; Kumar, N. N.; Reddy, M.
S.; Prasad, A. R. Tetrahedron 2006, 63, 2689–2694; (h) Rao, A. V. R.; Reddy, E. R.;
Joshi, B. V.; Yadav, J. S. Tetrahedron Lett. 1987, 28, 6497–6500.
in all respects (1H NMR, 13C NMR, IR, Rf and [
a]D) to the naturally
isolated compound.1,9
In summary, we have described a concise and convergent ap-
proach to basiliskamides A and B via a common intermediate using
our recently developed synthetic sequence for polyketide precur-
sors. This approach can provide a means for probing the struc-
ture–activity relationships of these and other related antifungal
agents.
5. Org. Synth. 1993 Coll. Vol. 8, 367; 1990, 69, 212.
6. Mitsunobu, O. Synthesis 1981, 1–28.
7. (a) Becket, H.; Soler, M. A.; Sharpless, K. B. Tetrahedron 1995, 51, 1345–1376; (b)
Andrus, M. B.; Lepore, S. D.; Sclafani, J. A. Tetrahedron Lett. 1997, 38, 4043–4046.
8. (a) Takai, K.; Nitta, K.; Utimoto, K. J. Am. Chem. Soc. 1986, 108, 7408–7410; (b)
Evans, D. A.; Black, W. C. J. Am. Chem. Soc. 1992, 114, 2260–2262; (c) Evans, D. A.;
Black, W. C. J. Am. Chem. Soc. 1993, 115, 4497–4513.
9. Data for selected compounds. Compound 11: Colourless liquid; ½a D20
ꢁ
+2.7 (c 1.0,
CHCl3); Rf = 0.5 (EtOAc/hexane, 1:9); IR (KBr): mmax 3373, 2961, 1054 cmꢀ1
;
1H
Acknowledgement
NMR (300 MHz, CDCl3): d 3.61 (dd, 1H, J = 10.5, 5.2 Hz), 3.47 (dd, 1H, J = 10.5,
5.2 Hz), 3.37–3.24 (m, 2H), 2.91 (dd, 1H, J = 9.8, 1.5 Hz), 1.95 (ddd, 1H, J = 12.0,
6.0, 4.5 Hz), 1.56–1.12 (m, 5H), 0.92–0.85 (m, 15H), 0.84 (d, 3H, J = 6.7 Hz). 0.04
(s, 6H). 13C NMR (75 MHz, CDCl3): d 82.1, 76.1, 74.0, 66.4, 40.8, 37.8, 35.2, 27.1,
25.8, 18.3, 12.5, 12.2, 12.0, ꢀ5.3; HRMS (ESI): m/z calcd for C17H36O3Na [M+Na]+
P.P.R. and M.S.R. thank CSIR, New Delhi, for the award of
fellowship.
339.2331, found 339.2328. Compound 20: Yellow oil; ½a D20
ꢁ
+6.8 (c 1.05, CHCl3);
1H NMR
References and notes
Rf = 0.5 (EtOAc/hexane, 3:7); IR (KBr): mmax 3407, 2963, 1178 cmꢀ1
;
(300 MHz, CDCl3): d 7.80 (d, 2H, J = 8.3 Hz), 7.34 (d, 2H, J = 8.3 Hz), 4.00 (dd, 1H,
J = 9.8, 6.0 Hz), 3.94 (dd, 1H, J = 9.8, 4.5 Hz), 3.62–3.52 (m, 1H), 3.32 (ddd, 1H,
J = 12.0, 4.5, 2.2 Hz), 2.90 (dd, 1H, J = 9.8, 1.5 Hz), 2.49 (s, 3H), 1.94 (ddd, 1H,
J = 13.5, 9.8, 4.5 Hz), 1.59–1.16 (m, 5H), 0.93 (d, 3H, J = 6.7 Hz), 0.87 (t, 3H,
J = 7.5 Hz), 0.78 (d, 3H, J = 6.7 Hz). 13C NMR (75 MHz, CDCl3): d 144.7, 133.1,
129.8, 127.9, 82.6, 73.5, 72.7, 72.2, 40.6, 37.0, 35.2, 27.0, 21.6, 12.1, 12.0; HRMS
(ESI): m/z calcd for C18H28O5NaS [M+Na]+ 379.1555, found 379.1548. Compound
1. Barsby, T.; Kelly, M. T.; Andersen, R. J. J. Nat. Prod. 2002, 65, 1447–1451.
2. (a) Lipomi, D. J.; Langille, N. F.; Panek, J. S. Org. Lett. 2004, 6, 3533–3536; (b) Dias,
L. C.; Goncalves, C. C. S. Adv. Synth. Catal. 2008, 350, 1017–1021.
3. For the Prins cyclisation, see, for example: (a) Barry, C. St. J.; Crosby, S. R.;
Harding, J. R.; Hughes, R. A.; King, C. D.; Parker, G. D.; Willis, C. L. Org. Lett. 2003,
5, 2429–2432; (b) Yang, X.-F.; Mague, J. T.; Li, C.-J. J. Org. Chem. 2001, 66, 739–
747; (c) Aubele, D. L.; Wan, S.; Floreancig, P. E. Angew. Chem., Int. Ed. 2005, 44,
3485–3488; (d) Barry, C. S.; Bushby, N.; Harding, J. R.; Willis, C. S. Org. Lett. 2005,
7, 2683–2686; (e) Cossey, K. N.; Funk, R. L. J. Am. Chem. Soc. 2004, 126, 12216–
6: White solid; ½a D20
ꢁ
ꢀ76 (c 0.4, MeOH), lit.1
½
a 2D3
ꢁ
ꢀ78 (MeOH); Rf = 0.4 (EtOAc/
hexane, 9:1); IR (KBr): mmax 3344, 2961, 1672 cmꢀ1
;
1H NMR (300 MHz, DMSO-
d6): d 7.68–7.72 (m, 2H), 7.65 (d, 1H, J = 15.5 Hz), 7.38–7.41 (m, 4H), 7.31 (s, 1H),

5430
J. S. Yadav et al. / Tetrahedron Letters 49 (2008) 5427–5430
6.80 (s, 1H), 6.60 (d, 1H, J = 15.5 Hz), 6.30 (t, 1H, J = 11.8 Hz), 5.91 (dt, 1H,J = 14.8,
J = 15.8 Hz, 1H), 7.50 (dd, J = 15.1, 11.1 Hz, 1H), 7.41–7.38 (m, 3H), 7.34 (s,
1H), 6.85 (s, 1H), 6.58 (d, J = 15.8 Hz, 1H), 6.33 (t, J = 11.1 Hz, 1H), 5.87 (dt,
J = 14.4, 7.2 Hz, 1H), 5.57 (d, J = 11.1 Hz, 1H), 5.40 (dt, J = 9.8, 3.2 Hz, 1H), 4.47 (d,
1H, J = 6.5 Hz), 3.26 (m, 1H), 2.64–2.48 (m, 1H), 2.40–2.32 (m, 1H), 1.96–1.88 (m,
1H), 1.42–1.35 (m, 2H), 1.25–1.09 (m, 1H), 0.91–0.80 (m, 6H), 0.75 (d, J = 6.5 Hz,
3H); 13C NMR (75.0 MHz, DMSO-d6): d 167.4, 165.4, 143.7, 140.0, 138.0, 134.0,
130.0, 128.8, 128.5, 128.0, 119.6, 118.3, 73.9, 73.0, 36.2, 31.6, 26.5, 11.8, 11.6,
6.6 Hz), 5.56 (d, 1H, J = 11.1 Hz), 4.92 (m, 1H), 4.57 (d, 1H, J = 5.1 Hz), 3.49 (m,
1H), 2.33–2.24 (m, 1H), 2.08–1.97 (m, 2H), 1.72–1.63 (m, 1H), 1.30–1.02 (m, 2H),
0.96–0.78 (m, 9H); 13C NMR (75.0 MHz, DMSO-d6) d 167.6, 166.2, 144.7, 140.6,
134.0, 130.5, 129.0, 128.4, 128.2, 119.3, 118.0, 76.2, 69.6, 40.7, 35.6, 34.6, 26.4,
12.8, 11.6, 10.0; HRMS (ESI): m/z calcd for C23H31NO4Na [M+Na]+ 408.2150,
found 408.2170. Compound 7: White solid; ½a D20
ꢁ
ꢀ13 (c 0.8, MeOH), lit.1 a 2D3
½ ꢁ
ꢀ12 (MeOH); Rf = 0.4 (EtOAc/hexane, 9:1); IR (KBr): mmax 3350, 2962,
10.3; HRMS (ESI): m/z calcd for C
23H31NO4Na [M+Na]+ 408.2150, found
1704 cmꢀ1
;
1H NMR (300 MHz, CDCl3):
d
7.70–7.67 (m, 2H), 7.60 (d,
408.2163.