Studies towards the total synthesis of (-)-callystatin A

Article abstract of DOI:10.1016/j.tetlet.2011.05.151

The synthesis of C₁-C₁₂ and C₁₃-C ₂₂ fragments of (-)-callystatin A is accomplished employing desymmetrization strategy for the creation of five chiral centres of the polypropionate fragment and application of c

Full text of DOI:10.1016/j.tetlet.2011.05.151

Tetrahedron Letters 52 (2011) 4269–4272
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Tetrahedron Letters
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Studies towards the total synthesis of (ꢀ)-callystatin A
⇑
,
J. S. Yadav , K. Yadagiri, Ch. Madhuri, G. Sabitha
Organic Chemistry Division, CSIR, Indian Institute of Chemical Technology, Hyderabad 500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis of C1–C12 and C13–C22 fragments of (ꢀ)-callystatin A is accomplished employing desym-
metrization strategy for the creation of five chiral centers of the polypropionate fragment and application
of cross-metathesis (CM) reaction for the first time for this molecule.
Received 30 December 2010
Revised 25 May 2011
Accepted 31 May 2011
Available online 2 July 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
(ꢀ)-Callystatin A
Desymmetrization
Wadsworth–Emmons reaction
Cross-metathesis
2
In 1997, Kobayashi et al. isolated the potent antitumor polyke-
tide (ꢀ)-callystatin A (1) (Fig. 1) from the marine sponge Callyspon-
gia truncata.1 This unique natural product shows remarkable high
1
O
3
4
O
5
6
activity (IC50 = 10 pg/mL) against KB tumor cell lines and IC50
=
7
20 pg/mL against L1210 cells. Kobayashi group determined the
absolute configuration of the (ꢀ)-callystatin A via partial2 and total
synthesis3 by preparing several structural analogues, which led to
further insight on structure–activity relationships.4 The structure
of (ꢀ)-callystatin A contains a polypropionate chain and a lactone
ring connected to each other by two conjugated diene systems sep-
arated by two sp3 hybridised carbon atoms. Since callystatin A was
isolated in very small amounts (1 mg from 100 kg of sponge), at-
tracted more attention to provide material for extensive biological
evaluation, along with access to promising novel analogues, led to
considerable interest in (ꢀ)-callystatin A as a synthetic target. This
resulted in several total syntheses5 and fragment syntheses6 of the
molecule. Based on its intriguing structure and potent cytotoxicity
led us to take-up the synthesis of (ꢀ)-callystatin A.
22
24
17
19
8
12
10
14
16
20
18
23
21
9
13
15
11
O
OH
(-)-Callystatin A (1)
Figure 1.
its PMB ether followed by reduction of ester group using LiBH4 in
THF furnished alcohol 9 in 90% yield. The alcohol 9 was oxidized
to aldehyde followed by homologation with (methylene)triphenyl
phosphorane in dry THF using n-BuLi (1.6 M) to afford alkene 10 in
60% yield. The hydroboration of alkene 10 using BH3ꢁMe2S complex
in dry THF afforded primary alcohol, which was protected as its
TBDPS ether 11 in 92% yield using TBDPSCl, imidazole in dry
CH2Cl2. The oxidative deprotection of PMB group of compound
11 was accomplished using DDQ7 in CH2Cl2:H2O (9:1) to afford
the alcohol 12 in 85% yield. The oxidation of alcohol 12 using IBX
in DMSO and CH2Cl2 furnished aldehyde, which was then subjected
to Still’s modification of Horner-Wadsworth–Emmons8 reaction
using NaH and phosphonate salt S-I in dry THF at ꢀ78 °C to afford
Retrosynthetically, disconnecting the carbon backbone at C (6–
7) E-alkene and C (12–13) E-alkene thus dividing the target into
three key subunits 3–5 (Scheme 1). The subunit 5 could be acces-
sible from (S)-Roche ester 6 and the subunit 3 could be made from
a bicyclic olefin 8 using desymmetrization strategy. The fragment 2
could be made by a cross-metathesis reaction between a known vi-
nyl lactone 4 and the subunit 5.
the cis
a,b-unsaturated ester 13 as a major isomer in 88% yield
Synthetic strategy for C7–C12 fragment (5): synthesis of C7–C12
fragment 5 began with the protection of (S)-(+)-Roche ester 6 as
along with the traces of trans isomer, that could be separated by
column chromatography. The ester group in compound 13 was
converted in to alcohol using DIBAL-H to afford the allyl alcohol
14 in 90% yield (Scheme 2). The alcohol 14 was oxidized to alde-
hyde using IBX and one carbon extension was achieved by homol-
ogation of aldehyde with (methylene)triphenyl phosphorane in dry
⇑
Corresponding author. Tel.: +91 40 27193030; fax: +91 40 27160387.
E-mail addresses: yadav@iict.res.in, yadavpub@iict.res.in (J.S. Yadav).
College of Food and Agriculture Science, King Saud University, PO Box 2455,
Riyadh 11451, Saudi Arabia.
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.05.151

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J. S. Yadav et al. / Tetrahedron Letters 52 (2011) 4269–4272
2
1
O
4
O
6
7
12
17
19
22
24
9
15
13
O
OH
(1)
(-)-Callystatin A
O
O
Br-Bu3P+
OH OTBS
3
OH
2
O
O
O
OH
OH OBn OH OH
7
5
O
8
4
HO
COOMe
6
Scheme 1. Retrosynthetic analysis.
a
c
b
PMBO
OH
PMBO
HO
PMBO
COOMe
HO
OP
10
9
11
6
P = TBDPS
HO
CO2Et
13
e
f
d
OP
12 P = TBDPS
OP
OP
P = TBDPS
14
P = TBDPS
O
P
O
g
h
O
O
O
OH
OP
P = TBDPS
Phosphonate salt S-I
5
15
Scheme 2. Reagents and conditions. (a) (i) NaH, PMBBr, dry THF, 0 °C-rt, 3 h, 90%; (ii) LiBH4, EtOH, THF, ꢀ10 °C, 2 h. 90%; (b) (i) IBX, DMSO, dry CH2Cl2, 0 °C-rt, 2 h, 85%; (ii)
CH3PPh3+Brꢀ, n-BuLi, dry THF, ꢀ78 °C ꢀ0 °C, 5 h, 60%; (c) (i) BH3ꢁMe2S, NaOH, H2O2, dry THF, 0 °C, 4 h, 65%; (ii) imidazole, TBDPSCl, CH2Cl2, 0 °C-rt, 2 h, 92%; (d) DDQ,
CH2Cl2:H2O (9:1), 0 °C-rt, 2.5 h, 85%; (e) (i) IBX, DMSO, dry CH2Cl2, 0 °C-rt, 2 h, 82%; (ii) NaH, S-I, dry THF, 0 °C- ꢀ78 °C 1.5 h, 88%; (f) DIBAL-H, ꢀ78 °C, CH2Cl2, 2 h, 90%; (g) (i)
IBX, DMSO, dry CH2Cl2, 0 °C-rt, 2 h, 80%; (ii) CH3PPh3+Brꢀ, n-BuLi, dry THF, ꢀ78 °C ꢀ0 °C, 5 h, 65%; (h) TBAF, THF, 0 °C-rt, 1 h, 85%.
Coupling of C7–C12 fragment with a vinyl lactone (C1–C6 fragment):
O
O
the fragment 5 and the known vinyl lactone 49 in hand our next
attention was turned to couple them together (Scheme 3). Thus
the cross-metathesis reaction of 4 and 5 using Grubb’s second gen-
eration catalyst10 in dry benzene at 55 °C afforded the key frag-
ment 2 in 48% yield along with the dimer of 4.
O
O
4
OH
Grubbs-II Catalyst
5
Synthetic strategy for C13–C22 fragment (3): the synthesis of the
dry Ph-H 55 oC, 48%
OH
C
13–C22 fragment was started from a bicyclic olefin 16 (Scheme
2
4), prepared from ketone 8 as reported earlier.11 Asymmetric hyd-
roboration of olefin 16 using (ꢀ)-diisopinocamphenylborane12 pro-
ceeded smoothly to give the alcohol 17 with high enantiomeric
purity in 96% yield. The alcohol 17 was converted to the lactone
19 by a two step sequence, PCC oxidation of alcohol 17 followed
by Baeyer–Villiger oxidation of the resulting ketone 18. Alkylation
Scheme 3.
THF using n-BuLi (1.6 M) to afford diene 15 in 65% yield. The TBDPS
group of compound 15 was deprotected to afford the alcohol 5 in
85% yield using TBAF in THF, which completed the synthesis of
C7–C12 fragment in an overall 6% yield (Scheme 2).
at the
a-position of the lactone 19 was achieved by treating it with
ethyl iodide in the presence of LDA in dry THF at ꢀ78 °C to give a

J. S. Yadav et al. / Tetrahedron Letters 52 (2011) 4269–4272
4271
O
O
O
O
O
a
b
c
Ref 9
HO
O
O
OBn
O
O
OBn
OBn
f
OBn
19
16
17
8
18
O
O
e
d
g
OBn OTBS
22
OPiv
OTs
OBn OH OH
21
OPiv
OBn OH OH
7
OH
OBn
O
20
k
j
i
h
EtO2C
OH OTBS
25
OH OTBS
24
OH
Br
OBn OTBS
23
OH
m
l
Br-Bu3P+
HO
OH OTBS
OH OTBS
OH OTBS
27
26
3
Scheme 4. Reagents and conditions. (a) (ꢀ)-Ipc2BH, NaOH, H2O2, 7d, 96%; (b) PCC dry CH2Cl2, 0 °C-rt, 3 h, 85%; (c) m-CPBA, NaHCO3, 0 °C-rt, 2 h, 90%; (d) LDA, Ethyl iodide, dry
THF, ꢀ78 °C 5 h, 85%; (e) LAH, dry THF, 0 °C-rt, 4 h, 80%; (f) (i) 2,2-DMP, PPTS, 0 °C-rt, dry CH2Cl2, 12 h, 80%; (ii) pivolyl chloride, Et3N, dry CH2Cl2, 0 °C-rt, 12 h, 85%; (iii) p-
TsOH, MeOH, 0 °C-rt, 10 h, 75%; (g) (i) p-TsCl, n-Bu2SnO, Et3N, dry CH2Cl2, 0 °C-rt, 10 h, 70%; (ii) TBSTf, 2,6-lutidine, dry CH2Cl2, 0 °C-rt, 1 h, 85%; (h) LAH, dry THF, 0 °C-rt, 4 h,
85%; (i) Li, liq. NH3, dry THF, 30 min, 80%; (j) (i) dry DMSO, (COCl)2, Et3N, dry CH2Cl2, ꢀ78 °C; (ii) PPh3@CCH3CO2Et, dry benzene, rt, 12 h, 80% (over two steps); (k) DIBAL-H,
dry CH2Cl2, ꢀ78 °C, 2 h, 80%; (l) CBr4, PPh3, 2,6-lutidine, CH3CN, 30 min, 93%; (m) PBu3, CH3CN, 30 min.
compound 20 in 85% yield. Now, the attention was directed to-
wards the opening of lactone ring. Lactone 20 on treatment with
LAH in dry THF gave a polar compound in 80% yield, which was
found to be the expected triol 7 with the required five chiral cen-
tres (Scheme 4). 1,3-Diol group in 7 was protected as its acetonide
and the primary hydroxyl group was protected as its pivolate ester
using pivolyl chloride and Et3N in dry CH2Cl2 at 0 °C followed by
deprotection of acetonide group using catalytic amount of p-TsOH
in methanol to yield diol 21 in 75% yield. Diol 21 on selective pri-
mary tosylation with p-TsCl, Et3N and catalytic amount of n-dibu-
tyltin oxide at room temperature furnished mono tosylate and the
protection of secondary hydroxyl group as TBS ether using TBSOTf,
2,6-lutidine in dry CH2Cl2 which afforded 22 in 85% yield. Com-
pound 22 was refluxed with 2 equiv of LAH in dry THF which re-
sulted in tosyl group removal as well as pivolyl deprotection to
yield compound 23 in 80% yield. The compound 23 was subjected
to debenzylation using 10 equiv of Li metal in liq NH3 giving diol
24 in 80% yield. The primary hydroxyl group of diol 24 was selec-
tively oxidized under Swern13 oxidation conditions followed by
Wittig reaction with carbethoxyethylidene triphenylphosphorane
in refluxing dry CH2Cl2 to give
a,b-unsaturated ester 25 in 80%
yield for the two step sequence. The ester 25 on DIBAL-H reduction
gave allylic alcohol 26 in 80% yield, which was then converted to
allyl bromide 27 using PPh3, 2,6-lutidine and CBr4 in dry CH3CN
in 80% yield. The allylic bromide 27 was converted to its phospho-
nium salt 3 using PBu3, thus completing the synthesis of C13-C22
fragment in an overall 6.1% yield.
The alcohol 2 was converted to the corresponding aldehyde 28
in 65% yield using IBX in DMSO/CH2Cl2 (Scheme 5). Since the cou-
pling14 of 28 with the phosphonium salt 3 and the conversion of
coupling product to the synthesis of (ꢀ)-callystatin A is already re-
ported,5k this constitutes a formal synthesis of (ꢀ)-callystatin A.
In conclusion, we have accomplished the C1–C12 and C13–C22
Fragments of (ꢀ)-callystatin A in a highly convergent way, by using
O
O
O
O
a
Ref 14
+
Br-Bu3P+
Ref 5k
OH OTBS
O
OH
28
2
3
O
O
O
OH
1
(-)-Callystatin A
Grubbs' II catalyst
Scheme 5. Reagents and conditions. (a) IBX, dry CH2Cl2, DMSO, 2 h, 65%.

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J. S. Yadav et al. / Tetrahedron Letters 52 (2011) 4269–4272
(c 1, CHCl3); 1H NMR (CDCl3, 400 MHz): d 7.66 (m, 4H), 7.41–7.35 (m, 6H), 3.78–
3.64 (m, 2H), 3.51–3.41 (m, 2H), 2.29 (br s, 1H), 1.88–1.77 (m, 1H), 1.67–1.56 (m,
1H), 1.53–1.41 (m, 1H), 1.05 (s, 9H), 0.91 (d, 3H, J = 6.7 Hz); IR (neat): 3349, 3062,
2938, 2868, 1468, 1428, 1106, 1003, 815, 702 cmꢀ1; EIMS: 343 (M++1).
Ethyl (Z,4R)-6-[1-(tert-butyl)-1,1-diphenylsilyl]oxy-2-ethyl-4-methyl-2-hexenoate
desymmetrization strategy, HWE and cross-metathesis reactions
as key steps.
Acknowledgments
(13): ½a 2D5
ꢂ
: (+)25.6 (c 1, CHCl3);1H NMR (CDCl3, 300 MHz): d = 7.66–7.61 (m, 4H),
7.41–7.33 (m, 6H), 5.51 (d, 1H, J = 10.1 Hz), 4.14 (q, 2H, J = 7.1, 14.3 Hz), 3.61 (dt,
2H, J = 1.3, 5.8 Hz), 3.18–3.07 (m, 1H), 2.21 (q, 2H, J = 7.5, 15.2 Hz), 1.62–1.51 (m,
2H), 1.24 (t, 3H, J = 7.1 Hz), 1.02 (s, 9H), 0.99 (d, 3H, J = 3.3 Hz), 0.96 (t, 3H,
J = 2.6 Hz); 13C NMR (CDCl3, 75 MHz): d = 168.2, 144.9, 135.5, 133.9, 132.7, 129.4,
127.5, 62.2, 59.9, 40, 30.2, 27.2, 26.7, 20.8, 20.4, 19.2, 14.2, 13.6; IR (neat): 2961,
2932, 1713, 1644, 1107, 703 cmꢀ1; EIMS: 439 (M++1).
K.Y.G. thanks UGC, New Delhi for the award of fellowship.
Author acknowledges the partial support by King Saud University
for Global Research Network for Organic Synthesis (GRNOS).
References and notes
tert-Butyl[(3R,4Z)-5-ethyl-3-methyl-4,6-heptadienyl]oxydiphenylsilane
(15):
½
a 2D5
ꢂ
: (ꢀ)4.4 (c 1, CHCl3); 1H NMR (CDCl3, 400 MHz): d = 7.64–7.59 (m, 4H),
7.38–7.29 (m, 6H), 6.69 (dd, 1H, J = 11.3, 17.4 Hz), 5.19 (d, 1H, J = 17.4 Hz), 5.02
(dd, 2H, J = 9.2, 21.5 Hz), 3.59 (t, 2H, J = 7.1 Hz), 2.92–2.84 (m, 1H), 2.16 (q, 2H,
J = 7.1, 14.3 Hz), 1.63–1.56 (m, 1H), 1.46–1.36 (m, 1H), 1.03 (s, 9H), 1.02 (t, 3H,
J = 7.1 Hz), 0.95 (d, 3H, J = 6.1 Hz); 13C NMR (CDCl3, 75 MHz): d 137, 135.5, 134,
133.2, 129.4, 127.5, 112.6, 61.8, 40.7, 27.8, 26.9, 25.8, 21.3, 19.1, 13.4; IR (neat):
2959, 2930, 2861, 1640, 1592, 1463, 1107, 988, 702 cmꢀ1; EIMS: 393 (M++1).
1. Kobayashi, M.; Higuchi, K.; Murakami, N.; Tajima, H.; Aoki, S. Tetrahedron Lett.
1997, 38, 2859–2862.
2. Murakami, N.; Wang, W.; Aoki, M.; Tsutsui, Y.; Higuchi, K. M.; Aoki, S.;
Kobayashi, M. Tetrahedron Lett. 1997, 38, 5533–5536.
3. Murakami, N.; Wang, W.; Aoki, M.; Tsutsui, Y.; Sugimoto, M.; Kobayashi, M.
Tetrahedron Lett. 1998, 39, 2349–2352.
4. Murakami, N.; Sugimoto, M.; Nakajima, T.; Kawanishi, M.; Tsutsui, Y.;
Kobayashi, M. Bioorg. Med. Chem. 2000, 8, 2651–2661.
5. (a) Crimmins, M. T.; King, B. W. J. Am. Chem. Soc. 1998, 120, 9084–9085; (b)
Smith, A. B., III; Brandt, B. M. Org. Lett. 2001, 3, 1685–1688; (c) Kalesse, M.;
Quitschalle, M.; Khandavalli, C. P.; Saeed, A. Org. Lett. 2001, 3, 3107–3109; (d)
Kalesse, M.; Chary, K. P.; Quitschalle, M.; Burzlaff, A.; Kasper, C.; Scheper, T.
Chem. Eur. J. 2003, 9, 1129–1136; (e) Vicario, J. L.; Job, A.; Wolberg, M.; Muller,
M.; Enders, D. Org. Lett. 2002, 4, 1023–1026; (f) Enders, D.; Vicario, J. L.; Job, A.;
Wolberg, M.; Muller, M. Chem. Eur. J. 2002, 8, 4272–4284; (g) Lautens, M.;
Stammers, T. A. Synthesis 2002, 1993–2012; (h) Marshall, J. A.; Bourbeau, M. P.
J. Org. Chem. 2002, 67, 2751–2754; (i) Marshall, J. A.; Bourbeau, M. P. Org. Lett.
2002, 4, 3931–3934; (j) Langille, N. F.; Panek, J. S. Org. Lett. 2004, 6, 3203–3206;
(k) Dias, C. L.; Meria, R. R. P. J. Org. Chem. 2005, 70, 4762–4773; (l) Reichard, H.
A.; Rieger, J. C.; Micalizio, G. C. Angew. Chem. Int. Ed. 2008, 47, 7837–7840.
6. (a) Dias, C. L.; Meria, R. R. P. Tetrahedron Lett. 2002, 43, 8883–8885; (b)
Marshall, J. A.; Fitzgerald, R. N. J. Org. Chem. 1999, 64, 4477–4481.
7. Harika, K.; Yoshika, T.; Oikawa, Y.; Yonemitsu, O. Tetrahedron 1986, 42, 3021–
3028.
8. Still, W. C.; Gennari, C. Tetrahedron Lett. 1983, 24, 4405–4408.
9. (a) Sabitha, G.; Reddy, C. N.; Gopal, P.; Yadav, J. S. Tetrahedron Lett. 2010, 51,
5736–5739; (b) Sabitha, G.; Reddy, S. S.; Yadav, J. S. Tetrahedron Lett. 2010, 51,
6259–6261.
10. Chatterjee, K. A.; Choi, L. T.; Sanders, P. D.; Grubb’s, H. R. J. Am. Chem. Soc. 2003,
125, 11360.
11. (a) Yadav, J. S.; Padmavani, B.; Venugopal, Ch. Tetrahedron Lett. 2009, 50, 3772–
3775; (b) Yadav, J. S.; Hossain, S. K.; Mohapatra, D. K. Tetrahedron Lett. 2010, 51,
4179–4181; (c) Yadav, J. S.; Reddy, K. B.; Sabitha, G. Tetrahedron Lett. 2004, 45,
6475–6476.
12. Browm, H. C.; Varaprasad, J. V. N. J. Am. Chem. Soc. 1986, 108, 2049–2054.
13. Mancuso, A. J.; Swern, D. Synthesis 1981, 165–185.
(3R,4Z)-5-Ethyl-3-methyl-4,6-heptadien-1-ol (5): ½a D25
ꢂ
: (ꢀ)30.0 (c 1, CHCl3); 1H
NMR (CDCl3, 300 MHz): d = 6.66 (dd, 1H, J = 10.7, 17.5 Hz), 5.22 (d, 1H,
J = 17.5 Hz), 5.09 (dd, 2H, J = 10.7, 20.5 Hz), 3.62–3.52 (m, 2H), 2.83–2.76 (m,
1H), 2.20 (q, 2H, J = 7.8, 15.6 Hz), 1.66–1.59 (m, 1H), 1.48–1.4 (m, 1H), 1.06 (t, 3H,
J = 7.8 Hz), 0.99 (d, 3H, J = 6.8 Hz); 13C NMR (CDCl3, 75 MHz): d = 139.8, 134.9,
132.7, 113.8, 61.2, 40.3, 28.3, 25.8, 21.5, 13.4;IR (neat): 3484, 2962, 2873, 1639,
1457, 1057, 993, 902 cmꢀ1; EIMS: 177 (M++23).
2R,3R,4S,5R,6R)-5-(Benzyloxy)-2-ethyl-4,6-dimethylheptane-1,3,7-triol (7): ½a D25
ꢂ
:
(ꢀ) 4.5 (c 1, CHCl3); 1H NMR (CDCl3, 300 MHz): d = 7.30 (m, 5H), 4.65 (s, 2H),
3.96–3.49 (m, 6H), 2.07–1.84 (m, 2H), 1.65–1.51 (m, 1H), 1.29–1.17 (m, 1H), 1.12
(d, 3H, J = 7.5 Hz), 1.10–0.98 (m, 1H), 0.96 (d, 3H, J = 7.5 Hz), 0.92 (t, 3H,
J = 6.7 Hz); 13C NMR (CDCl3, 75 MHz): d = 137.5, 128.6, 128.1, 127.8, 127.1, 88.5,
76.3, 74.9, 65.3, 65.0, 43.8, 37.8, 35.5, 20.7, 14.7, 11.7, 11.3; IR (neat): 3419, 3295,
2963, 1042 cmꢀ1; FAB mass: m/z 311 (M++1).
(2R,3R,4R,5R,6R)-3-(Benzyloxy)-5-[1-(tert-butyl)-1,1-dimethylsilyl]oxy-2,4-
dimethyl-6-([(4-methylphenyl)sulfonyl]oxymethyl)octyl pivalate (22): ½a D25
ꢂ
: (+)
5.4 (c 0.6, CHCl3); 1H NMR (CDCl3, 200 MHz): d = 7.72 (d, 2H, J = 8.1 Hz), 7.33–
7.29 (m, 7H), 4.57 (s, 2H), 4.27–4.07 (m, 2H), 3.98–3.89 (m, 3H), 3.33–3.27 (m,
1H), 2.44 (s, 3H), 2.16–1.68 (m, 3H), 1.34–1.41 (m, 2H), 1.20 (s, 9H), 1.10 (s, 3H),
0.88 (d, 3H, J = 6.8 Hz), 0.86 (s, 9H), 0.80 (t, 3H, J = 7.6 Hz), 0.06 (s, 3H), 0.01 (s,
3H); IR (neat): 2970, 1723, 1300, 1170 cmꢀ1; FAB mass: m/z 663 (M++1).
(E, 4R, 5R, 6R, 7R, 8S)-7-[1-(tert-Butyl)-1,1-dimethylsilyl] oxy-2,4,6,8-tetramethyl-
2-decene-1, 5-diol (26): ½a D25
ꢂ
: (+) 16.3 (c 1.5, CHCl3); 1H NMR (CDCl3, 200 MHz):
d = 5.55 (d, 1H, J = 9.5), 4.01 (s, 2H), 3.70 (t, 1H, J = 2.9 Hz), 3.61 (dd, 1H, J = 10.2,
2.2 Hz), 2.4–2.6 (m, 1H), 1.78–1.70 (m, 1H), 1.68 (d, 3H, J = 1.1 Hz), 1.6 (m, 1H),
1.40–1.20 (m, 2H), 1.05 (d, 3H, J = 6.9 Hz), 0.99 (d, 3H, J = 6.9 Hz), 0.91 (s, 9H),
0.90 (t, 3H, J = 7.3 Hz), 0.73 (d, 3H, J = 6.9 Hz), 0.10 (s, 3H), 0.06 (s, 3H); 13C NMR
(CDCl3, 75 MHz): d = 134.4, 126.5, 79.9, 76.1, 68.8, 40.8, 35.5, 34.5, 28.4, 25.4,
17.6, 14.9, 13.4, 11.6, ꢀ4.6, ꢀ5.1; IR (neat): 3423, 2930, 2360, 1219, 1013 cmꢀ1
;
FAB mass: m/z 359 (M++1).
(6R)-6-[(1E,3Z,5R)-3-Ethyl-7-hydroxy-5-methyl-1,3-heptadienyl]-5,6-dihydro-
14. Murakami, N.; Sugimoto, M.; Kobayashi, M. Bioorg. Med. Chem. 2001, 9, 57–67
Selected spectral data: 1-methoxy-4-([(2R)-2-methyl-3-butenyl]oxymethyl)
2H-2-pyranone (2): ½a D25
ꢂ
: (ꢀ) 38.5 (c 0.5, CHCl3); 1H NMR (CDCl3, 200 MHz):
benzene (10): ½a D25
ꢂ
: (ꢀ)22.2 (c 1, CHCl3); 1H NMR (CDCl3, 300 MHz): d = 7.19
d = 6.92–6.82 (m, 1H), 6.68 (d, 1H, J = 15.8 Hz), 6.03 (d, 1H, J = 9.8 Hz), 5.75 (dd,
1H, J = 6.6, 15.8 Hz), 5.19 (d, 1H, J = 9.8 Hz), 5.04–4.99 (m, 1H), 3.65–3.45 (m, 2H),
2.88–2.75 (m, 1H), 2.52–2.42 (m, 2H), 2.19 (q, 2H, J = 7.3 Hz), 1.68–1.56 (m, 1H),
1.49–1.37 (m, 1H), 1.07 (t, 3H, J = 7.3 Hz), 1.00 (d, 3H, J = 6.6 Hz); 13C NMR (CDCl3,
75 MHz): d = 164.5, 145.5, 140.8, 138.0, 137.2, 122.8, 121.8, 79.0, 61.2, 40.1, 30.1,
28.2, 21.2, 20.1, 13.8; IR (neat): 3430, 2967, 1715, 1647, 1457, 1382, 1248,
1052 cmꢀ1; FAB mass: m/z 273 (M++23).
(d, 2H, J = 8.3 Hz), 6.81 (d, 2H, J = 8.3 Hz), 5.81–5.69 (m, 1H), 5.01–4.96 (m, 2H),
4.41 (s, 2H), 3.79 (s, 3H), 3.34–3.19 (m, 2H), 2.51–2.41 (m, 1H), 1.02 (d, 3H,
J = 6.7 Hz); 13C NMR (CDCl3, 75 MHz): d = 159, 141.2, 130.5, 129.1, 113.9, 113.6,
74.6, 72.5, 55.1, 37.7, 16.5; IR (neat): 2959, 2854, 1612, 1515, 1247, 1092, 1036,
914 cmꢀ1; EIMS: 229 (M++23).
(2R)-4-[1-(tert-Butyl)-1,1-diphenylsilyl]oxy-2-methylbutan-1-ol (12): ½a D25
ꢂ
: (+)6.8