An Efficient Derivation of the Versatile Chiron Antipode 1-tert-Butyldimethylsilylpenta-1,4-diyn-3-ol: Application to the Synthesis of (15E,R,R)-Duryne

Article abstract of DOI:10.1021/jo9800513

The title chiron, 1-tert-butyldimethylsilylpenta-1,4-diyn-3-ol (5), an essential segment of various bioactive polyacetylenic alcohols, has been efficiently resolved via a lipase-catalyzed acylation strategy. Lipases from different Pseudomonas species and Candida rugosa (CRL) furnished its (S)-antipode (as esters) with 86-96% ee. However, the (R)-alcohol 5 could be prepared with acceptable enantiomeric purity (93% ee) only using CRL-vinyl acetate-diisopropyl ether as the reagent protocol and under double filtration conditions. The chiron alcohol was then extended to the target compound (15E,R,R)-duryne (I) by its pyranylation, alkylation with the required achiral C₂₀-α,ω-dibromide 15, and suitable functionalization.

Full text of DOI:10.1021/jo9800513

6128
J . Org. Chem. 1998, 63, 6128-6131
An Efficien t Der iva tion of th e Ver sa tile Ch ir on An tip od e
1-ter t-Bu tyld im eth ylsilylp en ta -1,4-d iyn -3-ol: Ap p lica tion to th e
Syn th esis of (15E,R,R)-Du r yn e
A. Sharma and S. Chattopadhyay*
Bio-Organic Division, Bhabha Atomic Research Centre, Mumbai-400 085, India
Received J anuary 12, 1998
The title chiron, 1-tert-butyldimethylsilylpenta-1,4-diyn-3-ol (5), an essential segment of various
bioactive polyacetylenic alcohols, has been efficiently resolved via a lipase-catalyzed acylation
strategy. Lipases from different Pseudomonas species and Candida rugosa (CRL) furnished its
(S)-antipode (as esters) with 86-96% ee. However, the (R)-alcohol 5 could be prepared with
acceptable enantiomeric purity (93% ee) only using CRL-vinyl acetate-diisopropyl ether as the
reagent protocol and under double filtration conditions. The chiron alcohol was then extended to
the target compound (15E,R,R)-duryne (I) by its pyranylation, alkylation with the required achiral
C20-R,ω-dibromide 15, and suitable functionalization.
Chirons with a small C-framework and possessing a
and is known to exhibit in vitro inhibitory activity against
the growth of P388 murine leukemia and several human
tumor cell lines. The absolute configurations of its two
stereogenic centers as well as the olefinic geometry at
C-15 are yet unresolved. Attempted correlation between
the optical rotation and absolute configuration even for
the homologues of these polyacetylenic alcohols has so
far been misleading.8 In this paper, we report the
synthesis of its (15E,R,R)-isomer. However, since our
strategy ensures availability of the key chiron in its
antipodal forms and involves fixation of the C-15 olefin
geometry via an acetylenic intermediate, the protocol can
be extended to all possible stereoisomers of the target
compound. So far only one synthesis of (()-I has been
reported,9 and to the best of our knowledge, this is the
first enantioselective synthesis of I.
From the retrosynthetic perspective, compound I can
be prepared by alkylation of two molecules of the chiron
by a symmetrical C20-unit with terminal electrophilic
centers and subsequent functionalization. On the basis
of this analysis, we proceeded for the synthesis as follows.
P r ep a r a tion of th e Ch ir on . The propargyl alcohol
derivative 15 was C-silylated with TBSCl (tert-butyldi-
methylsilyl chloride) to furnish 2. Its acid-catalyzed
deprotection10 gave the alcohol 3 which was oxidized with
buffered pyridinium chlorochromate (PCC)11 to furnish
the aldehyde 4. This on reaction with lithium acetylide
afforded the key racemic synthon 5. The next job was
the resolution of 5 for which its enzyme catalyzed trans-
esterification was attempted using different acylating
agents and lipases (Table 1). Previously, several groups
attempted12a-c lipase-catalyzed resolution of secondary
diverse array of functionalities are essential in designing
efficient enantiomeric syntheses of bioactive compounds.
Thus, preparation of these intermediates not only as-
sumes contemporary significance but also provides a
great challenge especially when these are not easily
amenable from the natural pool materials. The title
compound 1-tert-butyldimethylsilylpenta-1,4-diyn-3-ol (5)
is one such versatile chiron which can be derivatized to
different types of compounds.
Furthermore, this also constitutes the precursor chiral
segment of the bioactive polyacetylenic alcohols which
are of recent interest. These 1,4-enynic-3-ols, obtained
from marine sponges in the genera of Cribrochaline,1
Siphonochaline,2 Petrosia,3a,b etc. are attractive synthetic
targets due to their structural novelty and unprecedented
pharmacological activity. These compounds are known
to exhibit4 a very wide spectrum of bioactivity which
includes antibacterial, antifungal, cytotoxic, and antitu-
mor properties. Moreover, some of these even show
unusual differential cytotoxicity profiles for different
human tumor cell lines. Earlier, we have synthesized5,6
several such compounds in racemic form. However, in
view of the presence of stereogenic centers in these, lack
of their efficient enantioselective syntheses, and low
natural abundance, development of their enantioselective
syntheses might provide better bioassay results. Hence,
we developed an efficient synthesis of 5 and exploited it
for the synthesis of the polyacetylenic alcohol, duryne (I),
isolated7 from the Caribbean sponge, Cribrochalina dura.
Compound I is a symmetric long chain molecule (C30)
with the fragile 1,4-enyn-3-ol unit at its two terminals
(1) Gunasekera, S. P.; Faircloth, G. T. J . Org. Chem. 1990, 55, 6223.
(2) Rotem, M.; Kashman, Y. Tetrahedron Lett. 1979, 3193.
(3) (a) Fusetani, N.; Shiragaki, T.; Matsunaga, S.; Hashimoto, K.
Tetrahedron Lett. 1987, 28, 4313. (b) Cimino, G.; De Giulio, A.; De Rosa,
S.; De Stefano, S.; Sodano, G. J . Nat. Prod. 1985, 48, 22.
(4) Guo, Y.; Gavagnin, M.; Trivellone, E.; Cimino, G. J . Nat. Prod.
1995, 58, 712.
(5) Kulkarni, B. A.; Chattopadhyay, S.; Chattopadhyay, A.; Mam-
dapur, V. R. J . Org. Chem. 1993, 58, 5964.
(6) Kulkarni, B. A.; Chattopadhyay, A.; Mamdapur, V. R. Collect.
Czech. Chem. Commun. 1993, 58, 1711.
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M. R.; Prather, T. R.; Shoemaker, R. H.; Boyd, M. R. J . Nat. Prod.
1995, 58, 1801.
(9) Deshpande, V. H.; Upadhye, B. K.; Wakharkar, R. D. Tetrahe-
dron Lett. 1989, 30, 1991.
(10) Miyashita, M.; Yoshikoshi, A.; Grieco, P. A. J . Org. Chem. 1977,
42, 3772.
(11) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 2647.
(12) (a) Glanzer, B. I.; Faber, K.; Griengl, H. Tetrahedron 1987, 43,
5791. (b) Mori, K.; Akao, H. Tetrahedron 1980, 36, 91. (c) Burgess, K.;
J ennings, J . L. J . Am. Chem. Soc. 1991, 113, 6129. (d) Sharma, A.;
Sankaranarayanan, S.; Chattopadhyay, S. Biotech. Lett. 1996, 18, 1391.
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Thompson, W.; Snader, K. M. Tetrahedron Lett. 1987, 28, 1377.
S0022-3263(98)00051-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 08/07/1998

Derivation of 1-tert-Butyldimethylsilylpenta-1,4-diyn-3-ol
J . Org. Chem., Vol. 63, No. 18, 1998 6129
17
Ta ble 1. Lip a se-Ca ta lyzed Resolu tion of
1-ter t-Bu tyld im eth ylsilylp en ta -1,4-d iyn -3-ol (5)
subsequent bromination with Ph3P‚Br2 gave the re-
quired C20-synthon 15.
%
%
Syn th esis of (15E,R,R)-I. Alkylation of 2 mol of 7
with 15 in the presence of n-BuLi as the base gave
compound 16 in modest yield. Its desilylation was
carried out by treating with TBAF18 in THF to afford 17.
This on subsequent acidic deprotection furnished the diol
acylating
agent
%
ee of ee of
convrsn alcohol ester
entry lipase
solvent
1
PPL vinyl acetate diisopropyl
ether
PFL vinyl acetate CH2Cl2
nda
2
3
4
5
6
26
30
35
5
25
27
35
nd
71
87
86
91
nd
96
18. Stereo- and regioselective partial reduction of its
PFL TFEB
CH2Cl2
19ab
internal alkyne functionalities with Li/NH3
finally
PSL vinyl acetate vinyl acetate
CRL vinyl acetate hexane
CRL vinyl acetate diisopropyl
ether
CRL vinyl acetate diisopropyl
ether
gave (15E,R,R)-I (Scheme 1) whose spectral data were
similar to those reported.7 However, due to the uncer-
tainity of the absolute configuration as well as the olefinic
geometry at the C-15 position of natural I, no correlation
between the chiroptical data of natural and the synthetic
I was possible.
35
7
30b
93
nd
a
b
No appreciable conversion was noticed. Reaction done on the
partially resolved alcohol obtained from the previous entry.
alkynols via hydrolysis. Among these, the pioneering
contribution of Burgess and J ennings appears to be the
best for practical application. We have also reported12d
the first nonhydrolytic enzymatic protocol for the resolu-
tion of some alkyn-3-ols in organic medium. Among the
enzymes tried for the present work, only the lipases from
Pseudomonas and Candida were promising, (S)-5 being
the more reactive isomer in all the cases. With different
Pseudomonas lipases, although good enantioselection was
obtained for the (S)-esters the % ee’s of the resolved
alcohol (R)-5 were modest. In contrast, better enantio-
control was achieved using the Candida rugosa lipase
(CRL) in conjunction with vinyl acetate as the acylating
agent. Diisopropyl ether was the best solvent where at
35% conversion the (S)-acetate 6 and the resolved (R)-
alcohol 5 were obtained in 96% and 71% ee’s, respectively.
For its optical enrichment, the partially resolved alcohol
5 was reacetylated until 30% conversion, to obtain the
(R)-alcohol 5 with 93% ee. The efficacy of CRL for the
resolution of 5 is in corroboration with our recently
reported12d method for the resolution of alkyn-3-ols with
the same lipase. The % ee’s of the chirons were deter-
mined by the 1H NMR analyses of their (R)-MTPA
esters13 in the presence of Eu(fod)3. The signals for the
OMe protons appeared at δ 4.28 and 4.37, respectively,
for the compounds derived from (R)- and (S)-5. The (R)-
alcohol 5 was then pyranylated to give the synthon 7.
The absolute configurations of 5 and 6 were empirically
assigned on the basis of on our earlier result12d in CRL-
catalyzed acylation of alkyn-3-ols. For confirmation, 7
was converted to the known compound 3-octanol14 by
alkylation with 1-bromopropane, depyranylation, desi-
lylation, and hydrogenation. The optical data of the
synthetic sample corroborated with that of (S)-3-octanol,
and thus, the starting chiron was of opposite, i.e., (R)-
configuration since the Cahn-Ingold-Prelog priority
sequence is changed in the above transformations.
P r ep a r a tion of th e Ach ir a l C20-Un it. The easily
available bromohydrin 815 was pyranylated to afford
compound 9. On the other hand, the known alkynoic acid
1016 was reduced with LAH to furnish the alcohol 11
which on pyranylation gave the C11-unit 12.5 Its was
then alkylated at its alkyne terminus with the bromide
9 to afford 13. Its depyranylation to the diol 14 and
Exp er im en ta l Section
1-(Tetr a h yd r op yr a n yloxy)-2-p r op yn e (1). A mixture of
propargyl alcohol (10.0 g, 0.18 mol), DHP (3,4-dihydropyran)
(18.0 g, 0.21 mol), and PPTS (0.2 g) in CH2Cl2 (100 mL) was
stirred for 3 h. The reaction was quenched with 10% aqueous
NaHCO3, the organic layer was separated, and the aqueous
layer was extracted with CHCl3. The combined organic extract
was washed with water and brine and finally dried. Removal
of solvent in vacuo followed by column chromatography (silica
gel, 0-10% EtOAc/hexane) of the residue gave pure 15 (20.0
g, 80%): IR 3260, 2100, 880, 810 cm-1; 1H NMR δ 1.3-1.6 (m,
6H), 2.2 (t, J ) 1.2 Hz, 1H), 3.4-3.7 (m, 2H), 4.15 (d, J ) 2.1
Hz, 2H), 4.75 (br s, 1H). Anal. Calcd for C8H12O2: C, 68.54;
H, 8.63. Found: C, 68.68; H, 8.79.
1-(Tetr a h yd r op yr a n yloxy)-3-ter t-bu tyld im eth ylsilyl-2-
p r op yn e (2). To a cooled (-30 °C) and stirred solution of 1
(10.0 g, 0.07 mol) in THF (50 mL) was added n-BuLi (49.1 mL,
0.078 mol, 1.6 M in hexane). After 1 h, the reaction mixture
was cooled to -78 °C and TBSCl (12.9 g, 0.086 mol) in THF
(30 mL) added. Stirring was continued for 3 h at the same
temperature and at room temperature for an additional 3 h.
The reaction was quenched with an aqueous saturated NH4-
Cl solution, the organic layer was separated, and the aqueous
portion was extracted with ether. The combined organic
extract was washed with water and brine and finally dried.
Removal of solvent followed by column chromatography (silica
gel, 0-5% EtOAc/hexane) of the residue gave pure 2 (12.9 g,
1
71%): IR 2820, 2200, 880, 810 cm-1; H NMR δ 0.1 (s, 6H),
0.9 (s, 9H), 1.4-1.6 (m, 6H), 3.5-3.7 (m, 2H), 4.1 (s, 2H), 4.75
(br s, 1H). Anal. Calcd for C14H26O2Si: C, 66.08; H, 10.30.
Found: C, 65.87; H, 10.42.
3-ter t-Bu tyld im eth ylsilylp r op -2-yn -1-ol (3). A solution
of 2 (12.5 g, 0.049 mol) and PTS (0.1 g) in MeOH (30 mL) was
refluxed until depyranylation was complete (∼4 h). Most of
the solvent was removed in vacuo, the residue was dissolved
in EtOAc, and the organic extract was washed with water and
brine. After drying and removal of solvent, the crude product
was purified by column chromatography (silica gel, 0-15%
EtOAc/hexane) to furnish 3 (7.7 g, 92%): IR 3380, 2180, 1280
cm-1 1H NMR δ 0.1 (s, 6H), 0.93 (s, 9H), 1.9 (br s, D2O
;
exchangeable, 1H), 4.27 (s, 2H). Anal. Calcd for C9H18OSi:
C, 63.46; H, 10.65. Found: C, 63.68; H, 10.40.
3-ter t-Bu tyld im eth ylsilylp r op -2-yn a l (4). To a cooled (0
°C) and stirred mixture of 3 (7.5 g, 0.044 mol) and anhydrous
NaOAc (0.5 g, 6.0 mmol) in CH2Cl2 (30 mL) was added PCC
(14.3 g, 0.067 mol). After stirring for 3 h, the mixture was
diluted with an equal volume of ether and the organic extract
passed through a 2 in. pad of silica gel. The eluent on
(13) Dale, J . A.; Mosher, H. S. J . Am. Chem. Soc. 1973, 95, 512.
(14) Chattopadhyay, S.; Mamdapur, V. R.; Chadha, M. S. J . Chem.
Res., Synop. 1990, 235.
(15) Kang, K.; Kim, W. S.; Moon, B. H. Synthesis 1985, 1161.
(16) Vogel, A. I. Text Book of Practical Organic Chemistry; Longmans
Group: London, 1989; 5th p 510.
(17) Wiley: G. A.; Hershkowitz, R. L.; Rein, B. M.; Chung, B. C. J .
Am. Chem. Soc. 1964, 86, 964.
(18) Varma, R. S.; Lamture, J . B.; Varma, M. Tetrahedron Lett. 1993,
34, 3029.
(19) (a) Campbell, K. N.; Eby, L. T. J . Am. Chem. Soc. 1941, 63,
216. (b) Warthen, J . D.; J acobson, M. Synthesis 1973, 616.

6130 J . Org. Chem., Vol. 63, No. 18, 1998
Sharma and Chattopadhyay
Sch em e 1
concentration in vacuo gave 4 (5.6 g, 76%): IR 2720, 2180,
1720, 880, 810 cm-1
DHP (0.42 g, 5.0 mmol), and PPTS (0.05 g) in CH2Cl2 (15 mL)
was stirred at room temperature for 8 h. Usual isolation as
described earlier and column chromatography (silica gel, 5%
EtOAc/hexane) of the crude product furnished pure 7 (0.615
.
1-ter t-Bu tyld im eth ylsilylp en ta -1,4-d iyn -3-ol (5). To a
stirred and cooled (-40 °C) saturated solution of acetylene in
THF (50 mL) was added n-BuLi (30.6 mL, 0.049 mol, 1.6 M in
hexane) at the same temperature. After 0.5 h, 4 (5.5 g, 0.033
mol) in THF (20 mL) was introduced in the mixture which
was stirred for 3 h at -40 °C and for 12 h at room temperature.
It was poured in ice-water, the organic layer was separated,
and the aqueous portion was extracted with ether. The
combined extract was washed with water, brine, dried, and
concentrated. The product obtained was purified by column
chromatography over silica gel (0-15% EtOAc/hexane) to
g, 66%): [R]22 +12.6 (c 1.4, CHCl3); IR 880, 810 cm-1 1H
;
D
NMR δ 0.12 (s, 6H), 0.93 (s, 9H), 1.4-1.6 (m, 6H), 2.8-3.0 (m,
1H), 3.5-3.7 (m, 2H), 4.55 (br s, 1H), 4.95 (d, J ) 2.2 Hz, 1H).
Anal. Calcd for C16H26O2Si: C, 69.01; H, 9.41. Found: C,
68.88; H, 9.22.
1-(Tetr a h yd r op yr a n yloxy)-9-br om on on a n e (9). As de-
scribed for 1, the alcohol 815 (6.5 g, 0.029 mol) was pyranylated
with DHP (2.94 g, 0.035 mol) and PPTS (0.1 g) in CH2Cl2 (50
1
mL) to give compound 9 (7.52 g, 84%): IR 880, 810 cm-1; H
1
furnish 5 (3.9 g, 61%): IR 3440, 3300, 2180 cm-1; H NMR δ
NMR δ 1.34 (br s, 14H), 1.5-1.7 (m, 6H), 3.42 (t, J ) 6 Hz,
2H), 3.5-3.9 (m, 4H), 4.62 (br s, 1H).
0.11 (s, 6H), 0.95 (s, 9H), 1.5 (br s, D2O exchangeable, 1H),
2.5 (d, J ) 2.1 Hz, 1H), 5.1 (d, J ) 2.4 Hz, 1H). Anal. Calcd
for C11H18OSi: C, 67.98, H, 9.33. Found: C, 68.17; H, 9.57.
(S )-3-Ac e t o x y -1-t er t -b u t y ld im e t h y ls ily lp e n t a -1,4-
d iyn e (6). A mixture of 5 (2.0 g, 0.01 mol), vinyl acetate (1.72
g, 0.02 mol), and CRL (0.5 g) in diisopropyl ether (20 mL) was
stirred until 35% completion (∼32 h). The mixture was
filtered, the precipitated enzyme was washed with EtOAc, and
the extract was concentrated in vacuo. The residue was
chromatographed over silica gel column (0-15% EtOAc/
hexane) to give (R)-5 (1.14 g, 57%) and (S)-6 (0.754 g, 31%).
10-Un d ecyn -1-ol (11). To a stirred suspension of LAH (2.5
g, 0.066 mol) in ether (50 mL) was added the acid 1016 (10.0 g,
0.055 mol) in ether (50 mL). The mixture was refluxed for 4
h and brought to room temperature, and the excess hydride
was decomposed with aqueous saturated Na2SO4. The mixture
was filtered and the solid residue washed with ether. The
combined organic layer was concentrated in vacuo to yield 115
(7.8 g, 84%): IR 3380, 3300, 2210 cm-1; 1H NMR δ 1.29 (br s,
14H), 2.1-2.4 (m, 3H), 2.84 (br s, D2O exchangeable, 1H), 3.68
(t, J ) 7 Hz, 2H).
1-(Tetr a h yd r op yr a n yloxy)-10-u n d ecyn e (12). As de-
scribed for 1, compound 11 (7.5 g, 0.045 mol) was pyranylated
with DHP (4.5 g, 0.054 mol) in CH2Cl2 (100 mL) in the presence
of PPTS (0.2 g) to give the known compound 125 (10.12 g,
90%): IR 3300, 2110, 880 and 810 cm-1; 1H NMR δ 1.32 (br s,
14H), 1.4-1.6 (m, 6H), 2.2-2.4 (m, 3H), 3.2-3.7 (m, 4H), 4.5
(br s, 1H).
(R)-5: [R]22 +3.6 (c 1.6, CHCl3).
D
(S)-6: [R]22 -60.1 (c 1.2, CHCl3); IR 1730, 1210 cm-1; H
1
D
NMR δ 0.1 (s, 6H), 0.9 (s, 9H), 2.4 (s, 3H), 2.8-3.0 (m, 1H),
4.8-4.9 (m, 1H). Anal. Calcd for C13H20O2Si: C, 66.05; H,
8.53. Found: C, 66.19; H, 8.34.
Using the same protocol, (R)-5 (1.14 g, 5.9 mmol) obtained
above was acetylated with vinyl acetate (1.0 g, 11.8 mmol) until
30% completion (∼40 h). From the reaction mixture, optically
enriched 5 (0.684 g, 60%) was isolated as above.
Docos-10-yn e-1,20-d iol (14). To a cooled (-25 °C) and
stirred solution of 12 (2.52 g, 0.01 mol) in THF (30 mL) was
added n-BuLi (6.88 mL, 0.011 mol, 1.6 M in hexane). After
stirring for 0.5 h at the same temperature, the mixture was
cooled to -25 °C and HMPA (5 mL) was added followed by
(R)-5: [R]22 +5.9 (c 0.8, CHCl3).
D
(R)-3-(Tetr a h yd r op yr a n yloxy)-1-ter t-bu tyld im eth ylsi-
lylp en ta -1,4-d iyn e (7). A solution of (R)-5 (0.65 g, 3.4 mmol),

Derivation of 1-tert-Butyldimethylsilylpenta-1,4-diyn-3-ol
J . Org. Chem., Vol. 63, No. 18, 1998 6131
the bromide 9 (3.4 g, 0.011 mol) in THF (40 mL). Stirring was
continued for 6 h at the same temperature and at room
temperature for 16 h. The reaction was quenched with
aqueous saturated NH4Cl, the organic layer was separated,
and the aqueous portion was extracted with ether. The
combined organic extract was washed with water and brine
and dried. Removal of solvent followed by column chroma-
tography of the residue over silica gel (0-15% EtOAc/hexane)
[R]22D +6.4 (c 0.78, CHCl3); IR 2980, 1460, 1240 cm-1; 1H NMR
δ 0.12 (s, 12H), 0.93 (s, 18H), 1.32 (br s, 28H), 1.4-1.6 (br s,
12H), 1.8-2.0 (m, 4H), 2.05-2.2 (m, 4H), 3.4-3.55 (m, 2H),
3.6-3.8 (m, 2H), 4.6-4.7 (m, 2H), 4.9-5.05 (m, 2H). Anal.
Calcd for C52H86O4Si2: C, 75.12; H, 10.43. Found: C, 75.39;
H, 10.24.
(3S,28S)-Tr icon ta -1,4,15,26,29-p en tyn e-3,28-d iol (18).
The entire mixture was then taken in THF (10 mL), cooled to
-78 °C, and treated with a solution of TBAF (1.0 mL, 1.0
mmol, 1 M in THF). After stirring for 3 h, it was diluted with
ice-cooled water and extracted with EtOAc. The organic
extract was washed with water and brine and dried. Removal
of solvent followed by column chromatography (silica gel, 0-5%
ether/hexane) gave 17 (0.310 g, ∼quanitative).
1
gave pure 13 (3.25 g, 68%): IR 880 and 810 cm-1; H NMR δ
1.32 (br s, 28H), 1.4-1.6 (m, 12H), 1.9-2.2 (m, 4H), 3.2-3.8
(m, 8H), 4.53 (br s, 2H). Anal. Calcd for C30H54O4: C, 75.26;
H, 11.37. Found: C, 75.44; H, 11.61.
The above compound was then dissolved in MeOH (30 mL)
and refluxed for 4 h in the presence of PTS (0.1 g) to furnish
1
14 (1.86 g, 88%): mp 75 °C; IR 3380, 1060 cm-1; H NMR δ
A solution of 17 (0.310 g) and PTS (0.05 g) in MeOH (10
mL) was stirred for 16 h. The usual workup followed by
chromatography (silica gel, 0-15% ether/hexane) gave pure
18 (0.152 g, 68%): [R]22D +21.2 (c 1.12, CHCl3); IR 3400, 3310,
1.32 (s, 28H), 1.8-2.0 (m, 4H), 2.4 (br s, D2O exchangeable,
2H), 3.68 (t, J ) 7 Hz, 4H). Anal. Calcd for C20H38O2: C,
77.36; H, 12.33. Found: C, 77.48; H, 12.48.
2150, 1060 cm-1 1H NMR δ 1.32 (s, 28H), 1.7 (br s, D2O
;
1,20-Dibr om od ocos-10-yn e (15). To a cooled (0 °C) and
stirred solution of Ph3P (3.66 g, 13.94 mmol) in CH2Cl2 (40
mL) was added dropwise Br2 (2.32 mL, 12.8 mmol, 5.5 M in
CCl4). After 0.5 h, a solution of 14 (1.8 g, 5.8 mmol) and
pyridine (1.12 mL, 13.94 mmol) in CH2Cl2 (20 mL) was slowly
added to the reaction mixture and stirring was continued for
3 h. Most of the solvent was removed in vacuo, the residue
was thoroughly extracted with hexane, and the extract was
concentrated. The residue was again dissolved in hexane and
passed through a 6 in. pad of silica gel to furnish 15 (1.54 g,
61%): IR 2980, 1460, 1240 cm-1; 1H NMR δ 1.32 (s, 28H), 1.9-
2.2 (m, 4H), 3.42 (t, J ) 7 Hz, 4H).
(3R,28R)-1,30-Di-(ter t-bu tyld im eth ylsilyl)-3,28-d i-(tet-
r a h yd r op yr a n yloxy)-tr ia con ta -1,4,15,26,29-p en tyn e (16).
As described for 13, compound 7 (0.6 g, 2.16 mmol) was
alkylated with 15 (0.518 g, 1.19 mmol) in THF (25 mL) and
HMPA (2 mL) in the presence of n-BuLi (1.5 mL, 2.37 mmol,
1.6 M in hexane). The product was purified by column
chromatography (silica gel, 0-10% ether/hexane) to afford the
alkylated product 16 along with some unreacted starting
materials. It was not possible to purify the required product
by column chromatography and hence a small part of it was
purified by preparative TLC to give pure 16 (0.43 g, 48%):
exchangeable, 2H), 1.8-2.5 (m containing a d at δ 2.1, J )
2.5 Hz, 10H), 4.95 (d, J ) 6 Hz, 2H). Anal. Calcd for
C
30H42O2: C, 82.90; H, 9.74. Found: C, 82.75; H, 9.84.
(3R,28R,4E,15E,26E)-Tr iacon ta-1,29-diyn e-4,15,26-tr ien e-
3,28-d iol (I). To a stirred solution of 18 (0.15 g, 0.35 mmol)
in liquid NH3 (20 mL) at -78 °C was added Li metal (63.5
mg, 9.1 mmol) in pieces. The mixture was stirred for 3 h until
the blue color persisted. Solid NH4Cl was carefully added into
the mixture followed by ice-cold water, and the mixture was
extracted with ether. The ether layer was washed with water
and brine and dried. After removing the solvent, the residue
was purified by column chromatography (silica gel, 0-15%
ether/hexane) to give pure I (0.103 g, 68%): [R]22 +24.8 (c
D
0.84, CHCl3) (lit.7 [R]D +29 (c 2, CHCl3)); IR 3440, 3340, 2200,
1060, 970 cm-1; 1H NMR δ 1.2-1.4 (m containing a s at δ 1.29,
28H), 1.7-1.9 (m, 4H), 1.95-2.1 (m, 4H), 2.57 (d, J ) 2.1, 2H),
4.0 (br s, D2O exchangeable, 2H), 4.84 (dist d, J ) 2.1, 2H),
5.3-5.4 (m, 2H), 5.5-5.65 (m, 2H), 5.8-5.95 (m, 2H). Anal.
Calcd for C30H48O2: C, 81.76; H, 10.98. Found: C, 81.86; H,
10.71.
J O9800513