An expeditious synthesis of bistratamide H using a new fluorous protecting group

Article abstract of DOI:10.1016/j.tetlet.2005.10.144

A total synthesis of bistratamide H has been achieved using a new 'highly' fluorous amino protecting group, tris(perfluorodecyl)silylethoxylcarbonyl ( ^FTeoc) group. The synthetic intermediates were easily isolated by liquid-liquid extraction with fluorous solvent. The fluorous protecting group was demonstrated to be recycled.

Full text of DOI:10.1016/j.tetlet.2005.10.144

Tetrahedron
Letters
Tetrahedron Letters 47 (2006) 239–243
An expeditious synthesis of bistratamide H using
a new fluorous protecting group
Yutaka Nakamura,* Kazuo Okumura, Masaru Kojima and Seiji Takeuchi*
Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Niigata 956-8603, Japan
Received 31 August 2005; revised 14 October 2005; accepted 21 October 2005
Available online 15 November 2005
Abstract—A total synthesis of bistratamide H has been achieved using a new ÔhighlyÕ fluorous amino protecting group, tris(perfluoro-
decyl)silylethoxylcarbonyl (FTeoc) group. The synthetic intermediates were easily isolated by liquid–liquid extraction with fluorous
solvent. The fluorous protecting group was demonstrated to be recycled.
Ó 2005 Elsevier Ltd. All rights reserved.
Bistratamides and didmolamides were isolated from asci-
dians Lissoclinum bistratum and Didemnum molle in the
southern Philippines and in Madagascar, respectively.1
They are cyclic tri- or tetra-peptides of amino acids that
include thiazole, oxazole and oxazoline (Fig. 1). The
unique macrolactam structures and their bioactivities
such as moderate cytotoxic activity, anti-microbial and
anti-drug resistance properties have attracted synthetic
organic chemistsÕ interest. Among them, KellyÕs and
ShinÕs groups have recently synthesized some of bistrata-
mides independently according to their own methodolo-
gies of thiazole amino acid synthesis. Kelly described in
his reports that ÔConstruction of the thiazoles in these
macrolactams is central to their total synthesisÕ and found
a facile and efficient biomimetic synthesis of thiazoles
accomplished by treating N-acylated cysteine with bis(tri-
phenyl)oxodiphosphonium trifluoromethanesulfonate
followed by oxidation of the thiazolines employing acti-
vated MnO2.2 Shin and his co-workers have synthesized
bistratamide G in a high total yield by a modified Han-
tzschÕs method using thioamide and bromoacyl deriva-
tives of an oxazole amino acid as intermediates, which
were prepared from dehydropeptides. Coupling the thio-
amide and bromoacyl moieties of the intermediates led to
the thiazole amino acid part of bistratamide G.3
also synthesized didmolamines A and B by a solid
phase assembly of thiazole-containing amino acids.4
However the amino acids were prepared by the above
biomimetic synthetic methods without using the solid
support. Secondly, the modified HantzschÕs method
used by ShinÕs group includes thiocarbonylation of
a-amino acid amide with LawessonÕs reagent. In the
reaction, it is very difficult to separate the products from
unbearably bad smelling by-products by silica gel col-
umn chromatography. Partial racemization of the prod-
ucts during the reactions is another problem of this
method.
Unlike KellyÕs solid support synthesis, fluorous protect-
ing groups can be used from the beginning of the
modified HantzschÕs route for protecting amino groups
of a-amino acids. If fluorine atom contents of intermedi-
ates of the route are enough high, the fluorous interme-
diates can be separated clearly from organic by-products
including the bad smelling ones by liquid–liquid extrac-
tion with fluorous and organic solvents.5 Optimization
of the reaction conditions is expected to be accom-
plished by checking the enantiomeric purity of the fluor-
ous intermediates by HPLC with a chiral column to
avoid the racemization of the intermediates. An excel-
lent method using fluorous supports such as HfBz and
HfBn has already been reported by Inazu and his
co-workers for oligopeptide and oligosaccharide synthe-
ses.6 However, we wanted to synthesize bistratamide H
by using fluorous protecting groups in order to apply
our method also to a fluorous mixture synthesis.7
These interesting works prompted us to employ fluorous
technologies for an expeditious synthesis of bistratamide
H due to the following reasons. Firstly, KellyÕs group
Keywords: Bistratamide; Fluorous; Thiazoles; Oxazoles.
*
In an early stage of this work, we confirmed that Cur-
Corresponding author. Tel.: +81 250 25 5165; fax: +81 250 25
5021; e-mail: nakamura@niigata-pharm.ac.jp
ranÕs fluorous Boc-protecting group8 and Bannwarth
0040-4039/$ - see front matter Ó 2005 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2005.10.144

240
Y. Nakamura et al. / Tetrahedron Letters 47 (2006) 239–243
O
O
O
O
S
S
HO
O
O
S
N
N
N
N
H
H
O
H
O
H
O
NH
NH
N
N
N
N
N
N
N
Ph
Ph
HN
O
NH
HN
O
NH
HN
O
NH
HN
O
N
N
N
N
O
O
O
O
S
S
S
S
didmolamide A
didmolamide B
bistratamide G
Figure 1. Bistratamide and didmolamide macrolactams.
bistratamide H
F
type heavy fluorous Cbz-protecting group9 worked well
for valine to give the corresponding thiazole amino acid
derivative in good yield by a modified HantzschÕs meth-
od. However, the light fluorous Boc-protecting group is
more practical for small scale synthesis and the heavy
fluorous Cbz-protecting group was very unreactive to
hydrogenation over palladium on charcoal because of
inactivation of the catalyst by sulfur atom of thiazole
ring. Therefore we tried to prepare a new type of
protecting group suitable for the modified HantzschÕs
method and finally reached 2-[tri(perfluorodecyl)-
silyl]ethoxycarbonyl (FTeoc) group, a fluorous version
of 2-(trimethylsilyl)ethoxycarbonyl group.10 The fluor-
ous protecting group has a simple structure and thus
high fluorine atom content and can be deprotected
by tetrabutylammonium fluoride (TBAF). Fluorous
protecting agent, 2-[tris(perfluorodecyl)silyl]ethoxy-
carbonyl-O-succimide (FTeoc-OSu) was prepared as
shown in Scheme 1.
Valine 6 was reacted with Teoc-OSu 5 in the presence
of triethylamine in aqueous THF. After the reaction,
the reaction mixture was acidified and then extracted
with FC-72 and acetonitrile. Concentration of the FC-
72 layer gave N-FTeoc-valine (FTeoc-Val-OH; 7) in
quantitative yield. FTeoc-Val-OH 7 was reacted with
DCC and 1-hydroxybenzotriazle (HOBt) in THF and
then treated with an aqueous ammonia solution. The
reaction mixture was filtered to remove DCU and then
the filtrate was extracted with FC-72. Concentration of
the FC-72 layer gave N-FTeoc-Val-amide 8 in 98% yield.
The amide 8 was reacted with LawessonÕs reagent in
THF and then the reaction mixture was extracted with
FC-72 and acetonitrile. The bad smelling by-products
and the reagent were completely partitioned into an
organic layer. Therefore, N-FTeoc-Val-thioamide 9
obtained from the FC-72 layer was almost odourless.
The thioamide 9 was reacted with excess amount of
ethyl bromopyruvate in DME and then treated with tri-
fluoroacetic anhydride (TFAA) and pyridine. After
evaporating DME, the reaction mixture was extracted
with FC-72 and acetonitrile and the crude product ob-
tained from FC-72 layer was purified by silica gel col-
umn chromatography to provide N-FTeoc-thiazole
amino acid ester (FTeoc-Val-Thz-OEt; 10) in 80% yield
as waxy solid. The overall yield from valine was about
74%. Enantiomeric purity of the product 10 was deter-
mined to be higher than 99% ee by HPLC with a chiral
column, DAICEL CHIRALCEL OD-H.
Fluorous hydrosilane 1 was reacted with bromine in FC-
72 (perfluorohexane) to give the corresponding silylbrom-
ide 2 and then the silylbromide was reacted with vinyl
magnesium chloride to give vinylsilane 3 in 87% yield
via the two steps. The vinylsilane 3 was reacted with 9-
borabicyclo[3,3,1]nonane (9-BBN) and then treated with
hydrogen peroxide to give fluorous silylethanol 4 in 84%
yield.11 The silylethanol 4 was treated with triphosgene
and then reacted with N-hydroxysuccimide (HOSu).
After purification of the crude product by silica gel col-
umn chromatography, the fluorous protecting agent
FTeoc-OSu 5 was obtained in 97% yield as white solid.
The overall yield from the hydrosilane 1 was about 70%.
Another component of bistratamide H, oxazole amino
acid methyl ester (H-Val-MeOxz-OMe; 14) was pre-
pared from FTeoc-Val-OH 7 via four step reactions
(Scheme 3).
F
By using Teoc-OSu 5, we next examined a synthesis of
thiazole amino acid derivative from valine by the modi-
FTeoc-Val-OH 7 was coupled with threonine using benz-
fied HantzschÕs method (Scheme 2).
otriazol-1-yl-oxy-tris(dimethylamino)phosphonium hexa-
Br2
MgCl
(C8F17CH2CH2)3Si
(C8F17CH2CH2)3SiH
(C8F17CH2CH2)3SiBr
FC-72
Et2O
1
2
3
87% (2 steps)
O
1) Triphosgene/THF
2) HOSu-(i-Pr)2NH
1) 9-BBN/Et2O
2) H2O2, 3N NaOH
O
O
O
OH
(C8F17CH2CH2)3Si
N
(C8F17CH2CH2)3Si
O
97%
84%
5: FTeoc-OSu
4
Scheme 1. Preparation of fluorous protecting agent FTeoc-OSu.

Y. Nakamura et al. / Tetrahedron Letters 47 (2006) 239–243
241
1) DCC, HOBt
in THF
FTeoc-OSu, Et3N
OH
OH
NH2
FTeocHN
FTeocHN
2) NH4OH
H2N
THF-H2O
rt, 2 h
O
O
O
extracted with FC-72
(and CH3CN)
filtered DCUrea
extracted with FC-72
8
7
6
quant
98%
1) KHCO3
Br
CO2Et
O
Lawesson's reagent
THF
in DME
S
N
FTeocHN
NH2
S
FTeocHN
2) TFAA, pyridine
in DME
CO2Et
extracted with FC-72
(and CH3CN)
9
10
evaporated DME
extracted with FC-72(and CH3CN)
purified by SiO2 column
95%
80% (99% ee)
Scheme 2. Preparation on N-FTeoc-thiazole amino acid ester, FTeoc-Val-Thz-OEt, from valine.
HO
H2N
CO2Me
HCl
H
PEG-Burgess
dioxane-THF
BOP, i-Pr2NEt
N
CO2Me
O
FTeocHN
7
FTeocHN
THF
rt, 3 h
O
N
85 C, 4 h
HO
˚
CO2Me
evaporated THF
extracted with FC-72
(and CH3CN)
evaporated dioxane and THF
extracted with FC-72
(and CH3CN)
12
11
quant
70%
DBU, BrCCl3
CH2Cl2
TBAF
O
O
FTeocHN
H2N
THF
N
N
0 C then rt, 12 h
˚
CO2Me
CO2Me
13
14
evaporated CH2Cl2
extracted with FC-72 (and CH3CN)
purified by SiO2 column
evaporated THF
CH3CN-FC-72
purified by alumina column
79% (95% ee)
61%
Scheme 3. Preparation of methyloxazole amino acid methyl ester, H-Val-MeOxz-OMe, from N-FTeoc-valine.
fluorophosphate (BOP) and N,N-diisopropylethyl-
amine (i-Pr2NEt) in THF. Evaporation of THF, extrac-
tion of the residue with FC-72 and acetonitrile and con-
centration of the FC-72 layer gave FTeoc-Val-Thr-OMe
11 in quantitative yield. FTeoc-Val-Thr-OMe 11 was
cyclized using PEG-Burgess reagent12 in 1,4-dioxane
and THF (1:1 v/v). After the same work-up procedures,
N-FTeoc-oxazoline methyl ester 12 was obtained in 70%
yield. The oxazoline 12 was dehydrogenated with DBU
and bromotrichloromethane in dichloromethane.13 The
crude product obtained by the work-up was purified
by silica gel column chromatography to afford
N-FTeoc-oxazole amino acid methyl ester (FTeoc-Val-
MeOxz-OMe; 13) in 79% yield. Enantiomeric purity of
the product was determined to be higher than 95% ee
by HPLC with the chiral column. FTeoc-Val-MeOxz-
OMe 13 was deprotected with TBAF in THF. The crude
product obtained by the work-up was purified by neu-
tral alumina column chromatography to provide oxaz-
ole amino acid methyl ester (H-Val-MeOxz-OMe; 14)
in 61% yield.
Finally we tried to synthesize bistratamide H from
FTeoc-Val-Thz-OEt 10 and H-Val-MeOxz-OMe 14
(Scheme 4).
F
At first, Teoc-Val-Thz-OEt 10 was treated with TBAF
F
in THF to remove Teoc protecting group. After evap-
orating THF, the residue was extracted with water, chlo-
roform and FC-72. From chloroform layer, deprotected
thiazole amino acid ester (H-Val-Thz-OEt; 15) was ob-
tained in 82% yield. On the other hand, FTeoc-Val-
Thz-OEt 10 was treated with 1 M LiOH aqueous solu-
tion in THF and then the reaction mixture was acidified

242
Y. Nakamura et al. / Tetrahedron Letters 47 (2006) 239–243
H2O
ammonium salt
evaporated
S
1M LiOH
THF-H2O
THF
TBAF
THF
CHCl3
FC-72
H2N
S
S
FTeocHN
FTeocHN
N
N
N
CO2Et
CO2H
CO2Et
15
82%
16
acidified with citric acid
extracted with FC-72
10
98%
(C8F17CH2CH2)3SiF
22
recovered quantitatively
PyBOP
CO2Et
CO2H
S
S
FTeocHN
FTeocHN
i-Pr2NEt
1M LiOH
THF-H2O
N
N
H
H
15
16
+
N
N
N
N
THF
S
S
O
O
evaporated THF
acidified with citric acid
extracted with FC-72
evaporated THF
extracted with FC-72 (and CH3CN)
17
18
96%
92%
F, 52.34%
F, 53.15%
14
PyBOP
i-Pr2NEt
O
O
S
S
FTeocHN
FTeocHN
O
O
1M LiOH aq.
N
N
H
N
N
H
H
H
N
N
N
N
N
N
THF
THF
rt, 12 h
S
S
CO2Me
CO2H
O
O
evaporated THF
extracted with FC-72 (and CH3CN)
evaporated THF
acidified with citric acid
extracted with FC-72
20
88%
19
F, 48.03%
F, 48.37%
90%
O
N
S
O
H
N
O
S
PyBOP, DMAP
DMF-CH2Cl2
N
O
N
TBAF
H2N
N
N
H
H
N
N
NH
N
HN
O
THF, rt, 3 h
S
CO2H
35%
O
O
evaporated THF
dilute with MeOH
washed with FC-72
S
21
Bistratamide H
Scheme 4. Preparation of bistratamide H.
F
and extracted with FC-72. From the FC-72 layer,
N-FTeoc-thiazole amino acid (FTeoc-Val-Thz-OH; 16)
was obtained in 98% yield. The two thiazole amino acid
derivatives 15 and 16 were coupled by using benz-
otriazol-1-yl-oxy-trispyrrolidinophosphonium hexaflu-
orophosphate (PyBOP) and i-Pr2NEt in THF. After
the work-up, thiazole amino acid dipeptide ester
(FTeoc-Val-Thz-Val-Thz-OEt; 17) was obtained in 96%
yield. FTeoc-Val-Thz-Val-Thz-OEt 17 was treated with
1 M LiOH aqueous solution in THF. After evaporating
THF, the aqueous solution was acidified and extracted
with FC-72. From the FC-72 layer thiazole dipeptide
amino acid (FTeoc-Val-Thz-Val-Thz-OH;18) was ob-
tained in 92% yield. FTeoc-Val-Thz-Val-Thz-OH 18
was coupled with H-Val-MeOxz-OMe 14 by using Py-
BOP and i-Pr2NEt in THF. After the work-up, tripep-
tide methyl ester (FTeoc-Val-Thz-Val-Thz-Val-MeOxz-
OMe; 19) was obtained in 88% yield as amorphous
solid. Teoc-Val-Thz-Val-Thz-Val-MeOxz-OMe 19 was
treated with 1 M LiOH aqueous solution in THF. After
evaporating THF, the aqueous solution was acidified
and extracted with FC-72. From the FC-72 layer
FTeoc-Val-Thz-Val-Thz-Val-MeOxz-OH 20 was ob-
tained in 90% yield. FTeoc-Val-Thz-Val-Thz-Val-
MeOxz-OH 20 was treated with TBAF to remove FTeoc
protecting group in THF. After evaporating THF, the
residue was extracted with FC-72 and methanol. N,O-
Deprotected linear peptide 21 obtained from the meth-
anol layer was dissolved in DMF-CH2Cl2 (1:2 v/v)
and the solution was added very slowly to a solution
of PyBOP and DMAP in DMF-CH2Cl2 (1:2 v/v) with
maintaining high dilution conditions. The product was
purified with a preparative TLC to give bistratamide
H in 35% yield. The specific rotation, 13C and 1H
NMR spectra and MS analysis demonstrated that the
product was the desired compound.14

Y. Nakamura et al. / Tetrahedron Letters 47 (2006) 239–243
243
Angew. Chem., Int. Ed. 2003, 42, 83–85; (c) You, S.-L.;
Kelly, J. W. J. Org. Chem. 2003, 68, 9506–9509; (d) You,
S.-L.; Kelly, J. W. Chem. Eur. J. 2004, 10, 71–75; (e) You,
S.-L.; Kelly, J. W. Tetrahedron 2005, 61, 241–249.
3. (a) Shin, C.; Abe, C.; Yonezawa, Y. Chem. Lett. 2004, 33,
664–665; (b) Yonezawa, Y.; Tani, N.; Shin, C. Bull. Chem.
Soc. Jpn. 2005, 78, 1492–1499.
MgCl
Et2O
(C8F17CH2CH2)3Si
(C8F17CH2CH2)3SiF
reflux, 24 h
22
3
62%
Scheme 5. Attempt to recycle the recovered fluorous silylfluoride.
4. (a) You, S.-L.; Deechongkit, S.; Kelly, J. W. Org. Lett.
2004, 6, 2627–2630; (b) You, S.-L.; Kelly, J. W. Tetra-
hedron Lett. 2005, 46, 2567–2570.
5. (a) Crich, D.; Neelamkavil, S. J. Am. Chem. Soc. 2001,
123, 7449–7450; (b) Crich, D.; Neelamkavil, S. Tetra-
hedron 2002, 58, 3865–3870.
As to the fluorous product 22 that was obtained from
FC-72 layer on deprotection of FTeoc group with
TBAF, we were very pleased to find that a reaction of
the fluorous product 22 with vinyl magnesium chloride
in FC-72 provided vinyl silane 3 in moderate yield
(Scheme 5).15 1H NMR spectra of the vinyl silane prod-
uct 3 was the same as that of the sample obtained by the
reaction of tris(perfluorodecyl)silylbromide 2 with vinyl
magnesium chloride.16 Therefore the fluorous product
22 must be tris(perfluorodecyl)silylfluoride and have
6. (a) Mizuno, M.; Goto, K.; Miura, T.; Matsuura, T.;
Inazu, T. Tetrahedron Lett. 2004, 45, 3425–3428; (b) Goto,
K.; Miura, T.; Mizuno, M.; Takaki, H.; Imai, N.;
Murakami, Y.; Inazu, T. Synlett 2004, 2221–2223; (c)
Miura, T.; Satoh, A.; Goto, K.; Murakami, Y.; Imai, N.;
Inazu, T. Tetrahedron: Asymmetry 2005, 16, 3–6.
7. (a) Luo, Z.; Zhang, Q.; Oderaotoshi, Y.; Curran, D. P.
Science 2001, 291, 1766–1769; (b) Curran, D. P.; Furu-
kawa, T. Org. Lett. 2002, 4, 2233–2235; (c) Zhang, W.;
Luo, Z.; Chen, C. H.-T.; Curran, D. P. J. Am. Chem. Soc.
2002, 124, 10443–10450; (d) Zhang, Q.; Lu, H.; Richard,
C.; Curran, D. P. J. Am. Chem. Soc. 2004, 126, 36–37; (e)
Dandapani, S.; Jeske, M.; Curran, D. P. Proc. Natl. Acad.
Sci. U.S.A. 2004, 101, 12008–12012; (f) Manku, S.;
Curran, D. P. J. Org. Chem. 2005, 70, 4470–4473.
8. Luo, Z.; Williams, J.; Read, R. W.; Curran, D. P. J. Org.
Chem. 2001, 66, 4261–4266.
1
high purity judging from its H NMR spectra in FC-
72 (C6D6 was used as an external lock and standard).17
Identification of the fluorous product 22 and optimiza-
tion of the recycling process are now underway.
In conclusion, we synthesized bistratamide H expedi-
tiously by using the new fluorous protecting group.
The isolation of the fluorous intermediates by fluorous
liquid extraction was very easy and quick, although
the fluorine atom content was just about 48% at the final
stage. Optimization of the reactions was carried out as
usual by monitoring the reactions with TLC. The enan-
tiomeric purities of the fluorous intermediates were
checked by HPLC with a chiral column to find optimal
reaction conditions for avoiding racemization of the
products. In addition, the fluorous fragment from the
fluorous protecting group was demonstrated to be
recycled.
9. Schwinn, D.; Bannwarth, W. Helv. Chim. Acta 2002, 85,
255–264.
10. (a) Greene, T. W.; Wuts, P. G. M. Protective Groups in
Organic Synthesis, 3rd ed.; Wiley Interscience: New York,
´
1999; (b) Kocienski, P. J. Protecting Groups, 3rd ed.;
Georg Thieme: Stuttgart, 2005.
11. Soderquist, J. A.; Hassner, A. J. Organomet. Chem. 1978,
156, C12–C16.
12. Wipf, P.; Hayes, G. B. Tetrahedron 1998, 54, 6987–6998.
13. Williams, D. R.; Lowder, P. D.; Gu, Y.-G.; Brooks, D. A.
Tetrahedron Lett. 1997, 38, 331–334.
14
14. Data of synthetic bistratamide H: ½aꢀD ꢁ103.1 (c 0.385,
Acknowledgements
25
MeOH) (lit.½aꢀD ꢁ92.9 (c 1.1, MeOH)1a); 1H NMR
(250 MHz, DMSO-d6) d 0.89–0.99 (m, 12H), 2.14–2.28
(m, 3H), 2.59 (s, 3H), 5.07 (dd, 1H, J = 5.2 and 8.5 Hz),
5.36 (dd, 1H, J = 5.5 and 8.5 Hz), 5.45 (dd, 1H, J = 6.6
and 9.7 Hz), 8.33 (s, 1H), 8.35 (s, 1H), 8.37 (d, 1H,
J = 9.7 Hz), 8.50 (d, 1H, J = 8.5 Hz), 8.54 (d, 1H, 8.5 Hz);
13C NMR (63 MHz, DMSO-d6) d 11.5, 18.2, 18.3, 18.4,
18.8, 19.2, 33.0, 34.6, 34.8, 52.6, 54.8, 55.0, 125.0, 125.5,
128.0, 148.0, 148.5, 153.6, 159.2, 159.7, 159.9, 160.7, 168.7,
169.2; MALDI-TOFMS calcd for C25H32N6O4S2:
567.1810 [M+Na]+ found: 567.1955.
The authors would like to thank Professor Dennis P.
Curran, University of Pittsburgh and Professor Willi
Bannwarth, Albert-Ludwigs-Universitat Freiburg for
their helpful suggestions. They also would like to thank
Dr. Nobuto Hoshi, Noguchi Research Institute and Dr.
Naoto Takada, Central Glass International, Inc. for
their valuable advices about the fluorous silylfluoride
and Noguchi Research Institute for the Noguchi Fluor-
ous ProjectÕs Fund. This work has been done as a part of
the project.
15. (a) Ogi K. MasterÕs thesis, Tohoku University, 1973; (b)
Boutevin, B.; Guida-Pietrasanta, F.; Ratsimihety, A.;
Caporiccio, G. J. Fluorine Chem. 1995, 70, 53–57.
16. 1H NMR data of vinylsilane 3: (250 MHz, FC-72, external
C6D6 lock) d 6.39 (dd, 1H, J =3.9 and 14.7 Hz), 6.32 (dd,
1H, J = 14.7 and 20.2 Hz), 6.02 (dd, 1H, J = 3.9 and
20.2 Hz), 2.39–2.19 (m, 6H), 1.21–1.14 (m, 6H).
References and notes
1. (a) Perez, L. J.; Faulkner, D. J. J. Nat. Prod. 2003, 66,
247–250; (b) Rudi, A.; Chill, L.; Aknin, M.; Kashman, Y.
J. Nat. Prod. 2003, 66, 575–577.
2. (a) Raman, P.; Razavi, H.; Kelly, J. W. Org. Lett. 2000, 2,
3289–3292; (b) You, S.-L.; Razavi, H.; Kelly, J. W.
17. Data of fluorosilane 22: 1H NMR (250 MHz, FC-72,
external C6D6 lock) d 2.46–2.26 (m, 6H), 1.26–1.19 (m,
6H); CI-MS (negative, m/z, %) 1387.9 (15), 979.1 (100),
921.1 (91), 551.1 (17), 350.1 (15).