Total Syntheses of (+)-Secosyrins 1 and 2 and (+)-Syributins 1 and 2

Article abstract of DOI:10.1021/jo9711089

First total syntheses of (+)-secosyrins 1 and 2 and total syntheses of (+)-syributins 1 and 2 are described. The two chiral centers of diisopropyl tartrate were incorporated into target natural products. Stereoselective construction of the spiro skeleton of secosyrins could be realized by taking advantage of an alkyne-cobalt complex. The synthesis of these compounds established their relative and absolute stereochemistry unambiguously.

Full text of DOI:10.1021/jo9711089

J . Org. Chem. 1997, 62, 8095-8103
8095
Tota l Syn th eses of (+)-Secosyr in s 1 a n d 2 a n d (+)-Syr ibu tin s
1 a n d 2
Chisato Mukai,* Sameh M. Moharram, Satoru Azukizawa, and Miyoji Hanaoka*
Faculty of Pharmaceutical Sciences, Kanazawa University, Takara-machi, Kanazawa 920, J apan
Received J une 18, 1997X
First total syntheses of (+)-secosyrins 1 and 2 and total syntheses of (+)-syributins 1 and 2 are
described. The two chiral centers of diisopropyl tartrate were incorporated into target natural
products. Stereoselective construction of the spiro skeleton of secosyrins could be realized by taking
advantage of an alkyne-cobalt complex. The synthesis of these compounds established their relative
and absolute stereochemistry unambiguously.
In tr od u ction
In 1993, syringolides 1 and 2 (1 and 2, respectively,
Figure 1), novel nonproteinaceous low molecular weight
metabolites, were isolated from Pseudomonas syringae
pv. tomato.1 These oxygen-rich tricyclic compounds 1 and
2 have been found to be produced by bacteria expressing
avirulence gene D and to elicit a hypersensitive reaction
in soybean plants carrying the resistance gene Rpg4.
Because of biological interest as well as the intriguing
oxygen-rich tricyclic structure of these elicitors, several
papers2 on the total syntheses of syringolides 1 and 2
have been published. Two years after the first report on
the isolation of 1 and 2, Sims and co-workers3 isolated
four structurally related compounds, secosyrins 1 and 2
(3 and 4, respectively) and syributins 1 and 2 (5 and 6,
respectively) from the same medium. The structures of
the four newly isolated compounds were elucidated by
(i) spectroscopic evidence including comparison of NMR
data with those of syringolides 1 and 2, whose stereo-
chemistry was unambiguously established, and (ii) chemi-
cal methods. Although compounds 3-6 have rather
simpler structures and are not active elicitors, in sharp
contrast to structurally more complex syringolides 1 and
2, isolation of the former is particularly of interest since
they provide some suggestions for understanding their
biosynthetic pathway.
F igu r e 1.
(5) and (+)-syributin 2 (6) from the common starting
material diisopropyl D-tartrate.
Resu lts a n d Discu ssion
By taking the synthesis of all γ-lactone natural prod-
ucts 1-6 into account, our synthetic plan consisted of the
successive transformation of the simplest syributins (5
and 6) to more complex syringolides (1 and 2) through
intermediate secosyrins (3 and 4) according to the ret-
robiosynthetic process proposed by Sims.3 We envisioned
that the two stereogenic centers of D-tartaric acid would
be easily incorporated into the triol residue attached to
the butenolide skeleton of syributins (5 and 6). Acyl
group migration on a primary alcohol to a secondary
hydroxy group would be followed by intramolecular
Michael type cyclization, resulting in formation of seco-
syrins (3 and 4). Dieckmann type intramolecular ester
condensation reaction of 3 and 4 under proper conditions
would produce syringolides (1 and 2). This straightfor-
ward method might be the best method for efficient
syntheses of all γ-lactone natural products 1-6.
During our investigation on the total synthesis of the
title compounds, Honda et al.2f completed the first total
synthesis of (+)-syributin 1 (5) based on Sharpless
asymmetric dihydroxylation of an alkenyl butenolide
derivative. In this paper, we describe the first stereose-
lective total syntheses of (+)-secosyrin 1 (3)4 and (+)-
secosyrin 2 (4), as well as syntheses of (+)-syributin 1
* Tel: +81-76-234-4450. Fax: +81-762-34-4410. E-mail: cmukai@
kenroku.ipc.kanazawa-u.ac.jp.
X Abstract published in Advance ACS Abstracts, October 15, 1997.
(1) (a) Smith, M. J .; Mazzola, E. P.; Sims, J . J .; Midland, S. L.; Keen,
N. T.; Burton, V.; Staylon, M. M. Tetrahedron Lett. 1993, 34, 223. (b)
Midland, S. L.; Keen, N. T.; Sims, J . J .; Midland, M. M.; Staylon, M.
M.; Burton, V.; Smith, M. J .; Mazzola, E. P.; Graham, K. J .; Clardy, J .
J . Org. Chem. 1993, 58, 2940.
(2) (a) Wood, J . L.; J eong, S.; Salcedo, A.; J enkins, J . J . Org. Chem.
1995, 60, 286. (b) Kuwahara, S.; Moriguchi, M.; Miyagawa, K.; Konno,
M.; Komada, O. Tetrahedron Lett. 1995, 36, 3201. (c) Kuwahara, S.;
Moriguchi, M.; Miyagawa, K.; Konno, M.; Komada, O. Tetrahedron
1995, 32, 8809. (d) Henschke, J . P.; Rickards, R. W. Tetrahedron Lett.
1996, 37, 3557. (e) Ishihara, J .; Sugimoto, T.; Murai, A. Synlett 1996,
335. (f) Honda, T.; Mizutani, H.; Kanai, K. J . Org. Chem. 1996, 61,
9374.
Syn th esis of (+)-Syr ibu tin 1 a n d (+)-Syr ibu tin 2.
As our point of departure, the acetonide derivative 7,5
prepared from diisopropyl D-tartrate, was oxidized under
Swern conditions to give the aldehyde, which was sub-
sequently exposed to a Horner-Emmons reaction with
ethyl (diethylphosphono)acetate producing (E)-ester (+)-8
(3) Midland, S. L.; Keen, N. T.; Sims, J . J . J . Org. Chem. 1995, 60,
1118.
(4) The first total syntheis of (+)-secosyrin 1 (3) was reported as a
preliminary communication: Mukai, C.; Moharram, S. M.; Hanaoka,
M. Tetrahedron Lett. 1997, 38, 2511.
(5) Savage, I.; Thomas, E. J . J . Chem. Soc., Chem. Commun. 1989,
717.
S0022-3263(97)01108-0 CCC: $14.00 © 1997 American Chemical Society

8096 J . Org. Chem., Vol. 62, No. 23, 1997
Mukai et al.
Sch em e 1a
Sch em e 2
[R]24D +6.6 (c 0.6, CHCl3)] was obtained in 72% yield from
13 under acidic condition. On the other hand, (+)-
syributin 2 (6) [[R]17 +5.9 (c 0.18, CHCl3)] was also
D
synthesized in 69% yield from 14 via 12 (85% from 11).
Synthetic syributins 1 and 2 (5 and 6) were identified by
comparison of the 1H NMR spectra with those of the
naturally occurring compounds.
We next tried to convert the simplest monocyclic
butenolide derivatives into the corresponding more com-
plex bicyclic spiro derivatives. Acetonide and silyl pro-
tecing groups on the three hydroxy groups of the buteno-
lide 11 were removed by treatment with 10% hydrochloric
acid in methanol to give triol (-)-15 in 90% yield (Scheme
2). Intramolecular Michael type reaction of 15 leading
to 16 under both basic and acidic conditions such as
sodium hydride (NaH) in THF, lithium hexamethyldisi-
lazide (LHMDS) in THF, potassium tert-butoxide (KOBut)
in THF, KOH in EtOH, p-toluenesulfonic acid (p-TSA)
in THF, trifluoroacetic acid (TFA) in THF, and zinc iodide
(ZnI2) in THF unfortunately afforded an intractable
mixture or recovery of starting 15. It was at this point
that we noticed that the intramolecular Michael type
reaction of 15 was harder than imagined. Before chang-
ing this strategy, we investigated the direct transforma-
tion of 17 to target spiro compound 3. Compound (-)-
17 was prepared from 15 by successive acetonide
formation11 and acylation in 63% yield. Exposure of 17
to deacetonization conditions (20% hydrochloric acid in
THF at 0 °C) was shown to give (+)-syributin 1 (5)
instead of (+)-secosyrin 1 (3), accompanied with acyl
migration in a quantitative yield. Deacetonized com-
pound 18 without acyl migration could be detected on
TLC, but it was never isolated in more than trace
quantities. Presumably isomerization of 18 to 5 occurred
quickly during the isolation process. Similar unsuccess-
ful results2f on conversion of monocyclic compounds to
the corresponding spiro ones under several conditions
were reported by Honda et al. Because the first scenario
of our synthesis of all types of γ-lactone natural products
based on a retrobiosynthetic pathway was difficult, we
devised an alternative synthetic pathway for spiro de-
rivatives secosyrins 1 and 2 (3 and 4).
a
Reaction conditions: (a) (1) Swern oxidation, (2) (EtO)2-
POCH2CO2Et, NaH 85%; (b) CH3NO2, DBU, 80%; (c) (1) KOH,
(2) KMnO4, MgSO4, H2O, (3) NaBH4, 72%; (d) (1) LHMDS, TMSCl,
(2) Pd(OAc)2, benzoquinone, 74%; (e) TBAF, HF; (f) hexanoyl
chloride, Et3N, DMAP, 81%; (g) 10% HCl, 72%
in 85% yield (Scheme 1). Introduction of the C1-unit was
realized when 8 was treated with nitromethane in the
presence of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU)6 to
furnish (+)-9 in 80% yield. The stereochemistry at the
â position of 9 is not determined yet, since the newly
generated chiral center would disappear in further step.
However, it should be mentioned that 9 is made up of a
single isomer and is free from other stereoisomers.
Treatment of 9 with potassium hydroxide/potassium
permanganate (KMnO4)7 and sodium borohydride (NaBH4)
effected conversion of the nitromethyl group into an
aldehyde functionality; reduction and spontaneous lac-
tone formation provide the γ-lactone derivative (+)-10 in
72% yield. To prepare the butenolide skeleton, conven-
tional selenoxide chemistry8 was applied to 10 to afford
the desired (-)-11 in rather lower yield (40%). Alterna-
tively and more efficiently, (-)-11 was obtained in 74%
yield when trimethylsilyl enol ether derivative of 10 was
exposed to palladium diacetate.9 The final phase re-
quired for synthesis of syributins 1 and 2 (5 and 6) is
deprotection and acylation. Thus desilylation of 11 with
tetra-n-butylammonium fluoride (TBAF) and hydrofluoric
acid gave the primary alcohol 12, which was, without
isolation, acylated with hexanoyl chloride to leave (+)-
13 in 81% yield from 11. (+)-Syributin 1 (5) [[R]20D +7.8
(c 0.33, CHCl3); lit.10 [R]D +7.19 (c 0.86, CH2Cl2); lit.2f
Syn th esis of (+)-Secosyr in 1 a n d (+)-Secosyr in 2.
The most significant point for synthesis of secosyrins 1
and 2 (3 and 4) must be the stereoselective construction
of the quaternary center of 3 and 4. We anticipated that
(6) Ono, N.; Kamimura, A.; Kaji, A. Synthesis 1984, 226.
(7) Steliou, K.; Poupart, M.-A. J . Org. Chem. 1985, 50, 4971.
(8) Reich, H. J .; Renga, J . M.; Reich, I. L. J . Am. Chem. Soc. 1975,
97, 5434.
(9) Ito, Y.; Hirao, T.; Saegusa, T. J . Org. Chem. 1978, 43, 1011.
(10) Private communication from Professor J . J . Sims.
(11) Fanton, E.; Gelas, J .; Horton, D. J . Chem. Soc., Chem. Commun.
1980, 21.

Synthesis of Secosyrins and Syributins
J . Org. Chem., Vol. 62, No. 23, 1997 8097
Sch em e 3
F igu r e 2.
Debenzylation of 29 under hydrogenolysis conditions
in the presence of 10% Pd-C produced diol (+)-30 in 94%
yield. Selective monoacylation proceeded when 30 was
exposed to hexanoic anhydride in THF in the presence
of Et3N and DMAP to provide (+)-5-episecosyrin 1 (31)
the compound having an oxygen functionality at the R
position like 19 would react with the C2-unit via the
chelation model transition state A with a transient five-
membered ring, leading to the adduct 20 with desired
stereochemistry of 3 and 4. However, the possibility of
production of undesired product arising from the transi-
tion state B with a six-membered ring due to chelation
with the â oxygen functionality and/or a nonchelating
transtion state could not be ruled out.
[[R]26 +33.6 (c 0.12, CHCl3)] in 70% yield along with
D
diacylated compound (-)-32 (20%). Careful inspection
of the 1H NMR spectra of 5-episecosyrin 1 (31) and
secosyrin 1 (3) disclosed that both compounds show a
similar spectral pattern, except for their C9-protons. 9-H2
of 3 appear at δ 2.78 and 2.58 as an AB-quartet (J )
17.8 Hz), while those of 31 resonate at δ 2.86 and 2.75
as an AB-quartet (J ) 18.5 Hz). This diagnostic observa-
tion in the 1H NMR spectra, in combination with the
difference in their specific rotation [(+)-secosyrin 1 shows
its specific rotation10 of [R]D +42.85 (c 1.43, CH2Cl2)],
enabled us to distinguish (+)-secosyrin 1 (3) from 5-episec-
osyrin 1 (31).
We now had to develop an efficient way to invert the
tertiary hydroxy group at the propynyl center of 24 or
25. It is well-known that cobalt hexacarbonyl complexed
with propynyl alcohol derivatives, upon treatment with
acid, generate the corresponding propynyl cation, which
can be subsequently captured by various nucleophiles,
resulting in carbon-carbon and carbon-heteroatom bond
formation at the propynyl position (Nicholas reaction).16
We anticipated that the propynyl cation derived from the
cobalt complex of 25 would be intramolecularly captured
by primary alcohol through the transition state C (Figure
2) rather than the transition state D, the former of which
could lead to formation of a compound with the desired
stereochemistry. Transition state D would suffer from
serious nonbonding interactions between the bulky cobalt-
complexed alkyne portion and benzyloxy functionality in
an eclipsed form. This is not the case for the transition
state C, where unfavorable but rather weaker nonbond-
ing interaction of the benzyloxy group with the thioac-
etate residue might be the only nonbonding interaction
in existence. Formation of the transition state C, there-
fore, would be expected to be preferred over the transition
state D.
With the above consideration, we first prepared the
ketone derivative 23 with an acetylenic moiety as a C1-
unit. The hydroxy compound (-)-21,12 obtained from
diisopropyl tartrate, was consecutively oxidized under
Swern conditions and exposed to lithium phenylacetylide
to give 22 in 80% yield, which was again oxidized under
Swern condition to afford (-)-23 in 90% yield. Stereo-
selective introduction of the C2-unit was realized when
23 was treated with lithium enolate derived from tert-
butyl thioacetate at -78 °C in THF to provide (-)-24 in
94% yield as a sole product. Configuration of the newly
generated quaternary carbon center of 24 was uncertain
at this stage, although we expected that reaction would
have proceeded via the five-membered transition state
such as A (Scheme 3) and resulted in exclusive formation
of the desired product. To confirm the stereochemistry
of 24, it was converted into rigid spiro compound 29 by
conventional means. Desilylation of 24 with TBAF gave
(-)-25 (95%), which was subsequently treated with
p-toluenesulfonyl chloride (p-TsCl), triethylamine (Et3N),
and (dimethylamino)pyridine (DMAP) to produce the
tetrahydrofuran derivative (-)-26 in 89% yield. A NOE
experiment with 26 revealed 6.5% enhancement between
C4-H and C9-H.13 This observation indicated that the
configuration of the newly constructed quaternary center
of 24 was not that of 3 and 4. Hydrogenation of 26 in
the presence of Lindlar catalyst in ethyl acetate gave (-)-
27 in 75% yield. An alternative procedure for producing
27 was examined. Half-reduction of 25 furnished (+)-
28 (78%), ring closure of which was undertaken according
to the procedure described for conversion of 25 to 26,
providing 27 in 88% yield. Upon successive treatment
with ozone,14 NaBH4, and DBU, 27 underwent oxidative
cleavage of its olefinic portion, reduction, and ring closure
to afford spiro compound (+)-29 in 72% yield. X-ray
crystallographic analysis15 of (+)- 29 unambiguously
established its stereochemistry as depicted in Scheme 4,
thereby 24 was confirmed to have an undesired quater-
nary carbon center.
Dicobalt hexacarbonyl complex 33 was prepared in 98%
yield by treatment of 25 with Co2(CO)8 in diethyl ether
at room temperature (Scheme 5). Exposure of 33 to BF3‚-
(15) Crystal data: C21H22O5, M ) 354.40, orthorhombic, a ) 10.908-
(4) Å, b ) 19.07(1) Å, c ) 8.736(3) Å, V ) 1817(1) Å3, Z ) 4, Dc ) 1.295
g/cm3, Space group P212121 (#19), µ(Mo KR) ) 0.86 cm-1. A colorless
prismatic crystal, ca. 0.1 × 0.1 × 0.15 mm, was mounted on a glass
fiber. All measurements were made on a Rigaku AFC5R diffractometer.
The cell dimensions and intensities were refined by the least-squares
method, using 25 reflections on the diffractomer with Mo KR radiation
with w-scan mode for 2θ less than 55.0°. The structure was solved by
a direct method (MITHRIL method). The final cycle of full-matrix least-
squares refinement was based on 2167 observed reflections. The final
R value was 0.043.
(12) Mukai, C.; Moharram, S. M.; Kataoka, O.; Hanaoka, M. J .
Chem. Soc., Perkin Trans. 1 1995, 2849.
(13) Numbering for a 1,7-dioxaspiro[4.4]nonan-8-one skeleton was
used for convenience.
(16) Nicholas, K. M. Acc. Chem. Res 1987, 20, 207 and references
therein.
(14) Slomp, G., J r.; J ohnson, J . L. J . Am. Chem. Soc. 1958, 80, 915.

8098 J . Org. Chem., Vol. 62, No. 23, 1997
Mukai et al.
Sch em e 4
Sch em e 5
OEt2 in methylene chloride at room-temperature effected
ring closure with inversion of the configuration at the
quaternary center to provide tetrahydrofuran derivatives
with the cobalt complex, which were demetalated by
treatment with cerium(IV) ammonium nitrate (CAN) to
afford (+)-34 in 74% yield together with (-)-26 in 15%
yield. It should be mentioned that a NOE experiment
with 34 disclosed no enhancement between C4-H and
C9-H,13 in sharp contrast to the case of 26 (6.5%
enhancement). Thus efficient inversion of the propynyl
carbon center with concomitant ring formation was
realized. With desired 34 possessing the requisite qua-
ternary center, the stage was set for completing a first
total synthesis of secosyrins 1 and 2 (3 and 4). According
to the procedure developed for transformation of 26 into
5-episecosyrin 1 (31), 34 was half-reduced in the presence
of Lindlar catalyst to furnish (+)-35 in 78% yield. Spiro
ring construction was carried out by successive ozonoly-
sis, reduction, and base treatment to produce (+)-36 in
75% yield. Deprotection of 36 gave (+)-37 in 90% yield,
which was followed by monoacylation under aforemen-
tioned conditions to yield (+)-secosyrin 1 (3) [[R]26D +48.2
(c 0.12, CHCl3); lit.10 [R]D +42.85 (c 1.43, CH2Cl2)] along
with diacylated compound (-)-38. By changing the
acylating reagent from hexanoic anhydride to octanoic
quantitative conversion into (+)-syributin 1 (5) through
retro-Michael type reaction accompanied with migration
of hexanoyl group from secondary to primary hydroxy
group. This result is in good agreement with the bioge-
netic route proposed by Sims.
Con clu sion
Thus, we have succeeded in not only the first total
syntheses of (+)-secosyrins 1 and 2 but also the total
syntheses of (+)-syributins 1 and 2 from a common
starting material, diisopropyl D-tartrate. Although direct
transformation of simpler syributins into more complex
secosyrins by Michael type ring closure could not be
realized yet, the first total syntheses of (+)-secosyrins 1
and 2 have been accomplished in a stereoselective
fashion. And this synthesis established the structure of
(+)-secosyrins 1 and 2 unambiguously. Studies on the
synthesis of syringolides 1 and 2 in line with this program
are now in progress.
Exp er im en ta l Section
Melting points are uncorrected. IR spectra were measured
in CHCl3 unless otherwise mentioned. 1H NMR spectra were
taken in CDCl3 unless otherwise indicated. CHCl3 (7.26 ppm)
was used as an internal standard for silyl compounds. TMS
was employed as an internal standard for other compounds.
13C NMR spectra were recorded in CDCl3 with CDCl3 (77.00
ppm) as an internal standard. CH2Cl2 was freshly distilled
from phosphorus pentoxide and THF from sodium diphenyl
ketyl, prior to used. Silica gel (silica gel 60, 230-400 mesh,
Merck) was used for chromatography. Organic extracts were
dried over anhydrous Na2SO4.
anhydride, the diol 37 provided (+)-secosyrin 2 (4) [[R]21
D
+40.5 (c 0.10, CHCl3)] and (-)-39 in 78% and 15% yield,
respectively. Synthetic secosyrins 1 and 2 (3 and 4) were
identified by comparison with the spectral data of the
naturally occurring compounds. Specific rotation of
synthetic (+)-secosyrin 1 was also in good accordance
with that of natural (+)-secosyrin 1. It is noteworthy that
base treatment of secosyrin 1 (3) caused easy and

Synthesis of Secosyrins and Syributins
J . Org. Chem., Vol. 62, No. 23, 1997 8099
Eth yl (+)-(2E,4R,5R)-6-[(ter t-Bu tyld im eth ylsilyl)oxy]-
4,5-(isop r op ylid en ed ioxy)h exen oa te (8). A solution of
DMSO (0.22 mL, 3.07 mmol) in CH2Cl2 (3.0 mL) was added to
a solution of (COCl)2 (0.13 mL, 1.52 mmol) in CH2Cl2 (2.0 mL)
at -78 °C. After stirring for 15 min, a solution of 7 (212 mg,
0.77 mmol) in CH2Cl2 (3.0 mL) was added to the reaction
mixture and stirring was continued at the same temperature
for an additional hour. Et3N (0.64 mL, 4.61 mmol) was added
to the reaction mixture, which was then gradually warmed to
rt and diluted with CH2Cl2. the organic layer was washed with
water and brine, dried, and concentrated to dryness. The
crude aldehyde was used directly for the next reaction. To a
suspension of NaH (36.8 mg, 0.92 mmol) in THF (3.0 mL) was
added at 0 °C a solution of ethyl (diethylphosphono)acetate
(0.18 mL, 0.92 mmol) in THF (2.0 mL) and the mixture was
stirred for 30 min. A solution of the crude aldehyde in THF
(3.0 mL) was added to the reaction mixture, which was then
stirred for 20 min, quenched with water, and extracted with
ethyl acetate. The extract was dried and concentrated to leave
a residue, which was chromatographed with hexane-ethyl
acetate (25:1) to afford (+)-8 (225 mg, 85%) as a colorless oil:
(FAB) m/z 331 (M+ + 1, 19), 315 (23), 273 (52), 215 (39), 141
(25), 73 (100); IR 1775 cm-1; 1H NMR δ 4.39 (dd, 1H, J ) 7.3,
9.2 Hz), 4.24 (dd, 1H, J ) 7.3, 9.2 Hz), 3.96 (t, 1H, J ) 6.6
Hz), 3.79-3.60 (m, 3H), 2.84-2.66 (m, 1H), 2.54 (dd, 1H, J )
8.8, 17.5 Hz), 2.45 (dd, 1H, J ) 8.8, 17.5 Hz), 1.35 (s, 3H),
1.33 (s, 3H), 0.86 (s, 9H), 0.04 (s, 6H); 13C NMR δ 176.33,
109.20, 79.62, 79.50, 69.58, 63.67, 38.06, 31.04, 27.15, 26.97,
25.84, 18.28, -5.46, -5.53. Anal. Calcd for C16H30O5Si: C,
58.15; H, 9.15. Found: C, 57.75; H, 9.33.
(-)-(1′R ,2′R )-3-[3′-[(t er t -B u t y ld im e t h y ls ily l)o x y ]-
1′,2′-(isop r op ylid en ed ioxy)p r op yl]-2-bu ten -4-olid e (11).
Meth od 1. A solution of LHMDS (1M THF solution, 1.5
mL,1.5 mmol) was added dropwise to a solution of (+)-10 (330
mg, 1.0 mmol) in THF (10 mL) at -78 °C. After stirring at
-78 °C for 45 min, TMSCl (0.2 mL, 1.6 mmol) was added to
the reaction mixture, which was gradually warmed to rt with
stirring for 30 min. The mixture was concentrated, and the
resulting precipitates were filtered off by suction and washed
with dry ether. The filtrate was concentrated to afford the
crude silyl enol ether, which was dissolved in dry CH3CN (10
mL). Palladium acetate (112 mg, 0.5 mmol) and benzoquinone
(54.8 mg, 0.5 mmol) were added to the reaction mixture at rt,
and the mixture was stirred for 36 h and then filtered through
a pad of Celite.The filtrate was concentrated to dryness.
Chromatography of the residue with hexane-ethyl acetate (10:
1) provided (-)-11 (243 mg, 74%) as a colorless oil: [R]27D -4.8
(c 0.50, CHCl3); MS (FAB) m/z 329 (M+ + 1, 18), 313 (10), 271
(16), 213 (44), 89 (32), 73 (100), 59 (17); IR 1785, 1755, 1650
[R]27 +3.7 (c 0.50, CHCl3); MS (FAB) m/z 345 (M+ + 1, 9.9),
D
329 (28), 287 (41), 229 (100), 89 (85), 73 (100); IR 1715, 1665
cm-1; 1H NMR δ 6.94 (dd, 1H, J ) 4.9, 15.6 Hz), 6.12 (dd, 1H,
J ) 1.5, 15.6 Hz), 4.51 (ddd, 1H, J ) 1.5, 2.4, 4.9 Hz), 4.20 (q,
2H, J ) 6.8 Hz), 3.82 (dd, 1H, J ) 3.4, 8.3 Hz), 3.80 (dd, 1H,
J ) 3.4, 8.3 Hz), 3.75 (dt, 1H, J ) 2.4, 3.4 Hz), 1.43 (s, 3H),
1.42 (s, 3H), 1.29 (t, 3H, J ) 6.8 Hz), 0.9 (s, 9H), 0.07 (s, 3H),
0.07 (s, 3H); 13C NMR δ 166.07, 144.67, 121.87, 109.85, 80.72,
77.77, 62.72, 60.45, 26.88, 26.76, 25.90, 25.81, 18.24, 14.18,
-5.44, -5.48. Anal. Calcd for C10H32O5Si: C, 59.27; H, 9.36.
Found: C, 58.88; H, 9.51.
1
cm-1; H NMR δ 6.04 (q, 1H, J ) 2.0 Hz), 4.92 (dd, 1H, J )
2.0, 18.2 Hz), 4.81 (br s, 1H), 4.80 (ddd, 1H, J ) 1.0, 2.0, 18.2
Hz), 3.92 (ddd, 1H, J ) 1.7, 3.6, 6.3 Hz), 3.86 (dd, 1H, J ) 3.6,
10.6 Hz), 3.75 (dd, 1H, J ) 6.3, 10.6 Hz), 1.43 (s, 3H), 1.40 (s,
3H), 0.89 (s, 9H), 0.07 (s, 6H); 13C NMR δ 171.01, 167.44,
116.19, 110.41, 80.34, 75.44, 71.00, 63.07, 26.63, 26.44, 25.84,
18.35, -544, -5.51. Anal. Calcd for C16H28O5Si: C, 58.51; H,
8.59. Found: C, 58.25; H, 8.63.
E t h yl (+)-(4R,5R)-6-[(ter t-Bu t yld im et h ylsilyl)oxy]-3-
(n itr om eth yl)-4,5-(isop r op ylid en ed ioxy)h exa n oa te (9).
To a solution of (+)-8 (138 mg, 0.40 mmol) and nitromethane
(0.03 mL, 53 mmol) in CH3CN (3.0 mL) was added DBU (0.06
mL, 0.40 mmol) at rt. After stirring for 20 h, the reaction
mixture was quenched with water and extracted with ethyl
acetate. The organic layer was washed with water and brine,
dried, and concentrated to dryness. Chromatography of the
residue with hexane-ethyl acetate (25:1) afforded (+)-9 (130
Meth od 2. A solution of LHMDS (1 M THF solution, 0.82
mL, 0.82 mmol) was added dropwise to a solution of (+)-10
(90 mg, 0.27 mmol) in THF (2.0 mL) at -78 °C. After stirring
for 45 min, phenylselenenyl chloride (77.6 mg, 0.41 mmol) in
THF (1.5 mL) was added to the reaction mixture, which was
stirred at -78 °C for 1 h and then gradually warmed to 0 °C.
Addition of THF (1 mL) containing a trace of acetic acid to
the reaction mixture was followed by addition of a 30%
aqueous H2O2 solution (2.0 mL). After stirring for 30 min, the
reaction mixture was quenched by addition of saturated
NaHCO3 solution and extracted with ethyl acetate. The
extract was washed with water and brine, dried, and concen-
trated to dryness. Chromatography of the residue with
hexane-ethyl acetate (10:1) gave (-)-11 (35.8 mg, 40%).
(+)-(1′R,2′R)-3-[3′-(Hexa n oyloxy)-1′,2′-(isop r op ylid en e-
d ioxy)p r op yl]-2-bu ten -4-olid e (13). A solution of TBAF and
hydrofluoric acid (0.25 mL, prepared from 0.23 mL of 1.0 M
TBAF in THF solution and 0.02 mL of 47% hydrofluoric acid)
was added to a solution of (-)-11 (72.4 mg, 0.22 mmol) in THF
(3.0 mL) at rt. After consumption of 11 (monitered by TLC),
the reaction mixture was diluted with water and extracted
with ethyl acetate. The organic layer was washed with water,
dried, and concentrated to afford the alcohol 12, which was
directly used for the next reaction. To a solution of 12 in CH2-
Cl2 (3.0 mL) were successively added Et3N (0.04 mL, 0.26
mmol) and hexanoyl chloride (0.04 mL, 0.26 mmol) at 0 °C.
The mixture was warmed to rt with continued stirring for 3
h, diluted with water, and extracted with CH2Cl2. The extracts
were washed with water and brine, dried, and concentrated
to dryness. The residue was chromatographed with hexane-
ethyl acetate (10:2) to give (+)-13 (55.8 mg, 81%) as a colorless
mg, 80%) as a colorless oil: [R]27 +0.66 (c 0.52, CHCl3); MS
D
(FAB) m/z 406 (M+ + 1, 14), 390 (19), 348 (35), 290 (29), 283
1
(25), 73 (100), 59 (15); IR 1730, 1560, 1380 cm-1; H NMR δ
4.67 (dd, 1H, J ) 5.0, 13.5 Hz), 4.56 (dd, 1H, J ) 6.6, 13.5
Hz), 4.14 (q, 2H, J ) 6.9 Hz), 4.02 (t, 1H, J ) 6.7 Hz), 3.83
(ddd, 1H, J ) 4.0, 6.3, 6.7 Hz), 3.79 (dd, 1H, J ) 4.0, 10.6 Hz),
3.67 (dd, 1H, J ) 6.3, 10.6 Hz), 2.95-2.88 (m, 1H), 2.67 (dd,
1H, J ) 5.6, 16.8 Hz), 2.49 (dd, 1H, J ) 7.6, 16.8 Hz) 1.38 (s,
3H), 1.34 (s, 3H), 1.25 (t, 3H, J ) 6.9 Hz), 0.89 (s, 9H), 0.07 (s,
6H); 13C NMR δ 171.03, 109.34, 79.55, 79.07, 75.29, 63.95,
60.90, 36.91, 33.89, 27.01, 25.91, 25.84, 18.30, 14.07, -5.48,
-5.57. Anal. Calcd for C18H35NO7Si: C, 53.31; H, 8.70; N, 3.45.
Found: C, 53.15; H, 8.76; N, 3.41.
(+)-(1′R,2′R)-3-[3′-[(ter t-Bu t yld im et h ylsilyl)oxy]-1′,2′-
(isop r op ylid en ed ioxy)p r op yl]bu ta n -4-olid e (10). To a
solution of (+)-9 (4.05 g, 10 mmol) in EtOH (15 mL) was added
dropwise over a period of 45 min a solution of KOH (670 mg,
11.9 mmol) in EtOH (70 mL) at 0 °C. After stirring for 15
min, a solution of KMnO4 (1.06 g, 6.7 mmol) and MgSO4 (0.89
g, 7.4 mmol) in water (150 mL) was added dropwise over a
period 15 min to the reaction mixture at the same temperature
and stirring was continued for 30 min. The reaction mixture
was passed through a short pad of Celite and the residue was
washed with ethyl acetate. The filtrate was first saturated
with NaCl and then extracted with ethyl acetate. The extract
was dried and concentrated to afford the crude aldehyde, which
was directly used for the next reaction. To a solution of the
crude aldehyde in MeOH (25 mL) was added NaBH4 (378 mg,
10 mmol) portionwise at 0 °C. The reaction mixture was
gradually warmed to rt and stirred for 20 h. MeOH was
evaporated off to leave a residue, which was diluted with water
and extracted with ethyl acetate. The organic layer was dried
and concentrated to give an oily residue, which was chromato-
oil: [R]24 +12.2 (c 0.10, CHCl3); MS (FAB) m/z 313 (M+ + 1,
D
59), 297 (32), 225 (100), 137 (43), 99 (51), 43 (28); IR 1785,
1
1750 cm-1; H NMR δ 6.11 (q, 1H, J ) 2.0 Hz), 4.95 (dd, 1H,
J ) 2.0, 18.1 Hz), 4.80 (ddd, 1H, J ) 1.0, 2.0, 18.1 Hz), 4.73
(br d, 1H, J ) 8.3), 4.32 (dd, 1H, J ) 4.9, 12.2 Hz), 4.27 (dd,
1H, J ) 4.9, 12.2 Hz), 4.10 (dt, 1H, J ) 8.3, 4.9 Hz), 2.35 (t,
2H, J ) 7.8 Hz), 1.67-1.60 (m, 2H),1.47 (s, 3H), 1.44 (s, 3H),
1.34-1.28 (m, 4H), 0.90 (t, 3H, J ) 7.3); 13C NMR δ 173.30,
172.63, 165.77, 116.89, 111.05, 78.02, 74.57, 70.71, 62.64,
graphed with hexane-ethyl acetate (10:1) to afford (+)-10 (2.38
31
g, 72%) as a colorless oil: [R]
+9.7 (c 0.53, CHCl3); MS
D

8100 J . Org. Chem., Vol. 62, No. 23, 1997
Mukai et al.
33.91, 31.18, 26.60, 26.42, 24.44, 24.37, 22.21, 13.82. Anal.
Calcd for C16H24O6: C, 61.52; H, 7.74. Found: C, 61.23; H,
7.78.
for 20 min, the reaction mixture was quenched with water and
extracted with ether. The extract was dried and concentrated
to dryness. The residue was directly used for the next step.
To a solution of the crude acetonide derivative in CH2Cl2 (5.0
mL) were added Et3N (0.1 mL, 0.75 mmol) and hexanoyl
chloride (0.1 mL, 0.75 mmol) at 0 °C. The reaction mixture
was allowed to stand at rt for 2 h, quenched with water, and
extracted with CH2Cl2. The combined organic layers were
washed with saturated NaHCO3 solution, water, and brine,
dried, and concentrated to dryness. The residue was chro-
matographed with hexane-ethyl acetate (10:1) to give (-)-17
(+)-(1′R,2′R)-3-[1′,2′-(Isop r op ylid en ed ioxy)-3′-(octa n oy-
loxy)p r op yl]-2-bu ten -4-olid e (14). According to the proce-
dure that described the preparation of 13 from 11, compound
11 (72.2 mg, 0.22 mmol) was deprotected with a solution of
TBAF and hydrofluoric acid (0.25 mL, prepared from 0.23 mL
of 1.0 M TBAF in THF solution and 0.02 mL of 47% hydrof-
luoric acid) and then treated with Et3N (0.06 mL, 0.32 mmol)
and octanoyl chloride (0.05 mL, 0.32 mmol) in CH2Cl2 (3.0 mL)
to give (+)-14 (63.6 mg, 85%) as a colorless oil: [R]31D +13.6 (c
0.48, CHCl3); MS m/z 340 (M+, 0.21), 325 (100), 154 (77), 127
(124 mg, 63%) as a colorless oil: [R]20 -29.5 (c 0.11, CHCl3);
D
MS m/z 312 (M+, 4.7), 297 (34), 197 (30), 139 (25), 126 (19),
1
101 (100), 71 (29); IR 1785, 1755 cm-1; H NMR δ 6.05 (br s,
1
(61), 57 (51), 43 (85); IR 1785, 1750 cm-1; H NMR δ 6.11 (q,
1H, J ) 2.0 Hz), 5.79 (d, 1H, J ) 3.6 Hz), 4.93 (dd, 1H, J )
2.0, 17.8 Hz), 4.84 (dd,1H, J ) 2.0, 17.8 Hz), 4.36 (ddd, 1H, J
) 3.6, 5.6, 6.9 Hz), 4.08 (dd, 1H, J ) 6.9, 8.6 Hz), 3.79 (dd,
1H, J ) 5.6, 8.6 Hz), 2.40 (t, 2H, J ) 7.6 Hz), 1.73-1.59 (m,
2H),1.44 (s, 3H), 1.34 (s, 3H), 1.39-1.23 (m, 4H), 0.91 (t, 3H,
J ) 6.9 Hz); 13C NMR δ 172.56, 172.51, 164.37, 118.01, 110.41,
75.42, 71.65, 96.04, 65.25, 33.91, 31.14, 25.88, 24.78, 24.44,
22.18, 13.79. Anal. Calcd for C16H24O6: C, 61.52; H, 7.74.
Found: C, 61.28; H 7.77.
1H, J ) 2.0 Hz), 4.94 (dd, 1H, J ) 2.0, 18.1 Hz), 4.86 (ddd,
1H, J ) 1.0, 2.0, 18.1 Hz), 4.72 (br d, 1H, J ) 8.3), 4.32 (dd,
1H, J ) 4.9, 12.2 Hz), 4.27 (dd, 1H, J ) 4.9, 12.2 Hz), 4.09 (dt,
1H, J ) 8.3, 4.9 Hz), 2.35 (t, 2H, J ) 7.3 Hz), 1.68-1.58 (m,
2H),1.46 (s, 3H), 1.44 (s, 3H), 1.38-1.20 (m, 4H), 0.88 (t, 3H,
J ) 6.8 Hz); 13C NMR δ 173.33, 172.67, 165.79, 116.87, 111.05,
78.02, 74.56, 70.73, 62.64, 33.96, 31.56, 29.00, 28.83, 26.60,
26.42, 24.76, 22.52, 14.00. Anal. Calcd for C18H28O6: C, 63.51;
H, 8.29. Found: C, 63.28; H, 8.45.
(+)-Syr ibu tin 1 (5). To a solution of (+)-13 (150 mg, 0.48
mmol) in MeOH (7.0 mL) was added a solution of 5% HCl (2.0
mL). The reaction mixture was stirred at 45 °C for 2 h, and
then MeOH was evaporated off. The residue was neutralized
with saturated aqueous solution of NaHCO3 and extracted
with ethyl acetate. The extracts were dried and concentrated
to dryness to leave a residue, which was chromatographed with
ethyl acetate-hexane (10:4) to afford (+)-5 (94.2 mg, 72%) as
Con ver sion of (-)-17 in to (+)-5. To a solution of (-)-17
(62.4 mg, 0.20 mmol) was added 20% hydrochloric acid in THF
(2.0 mL) at 0 °C. The reaction mixture was stirred for 15 min,
quenched by saturated NH4Cl solution, and extracted with
ethyl acetate. The extract was washed with water and brine,
dried, and concentrated to dryness. Chromatography of the
residue with ethyl acetate-hexane (5:2) afforded (+)-5 (54 mg,
99%).
a colorless oil: [R]20 +7.8 (c 0.33, CHCl3) [lit.10 [R]D +7.19 (c
(-)-(4S,5R)-4,5-Bis(ben zyloxy)-6-[(ter t-bu tyld im eth yl-
silyl)oxy]-1-ph en yl-1-h exyn -3-on e (23). A solution of DMSO
(0.68 mL, 9.60 mmol) in CH2Cl2 (3.5 mL) was added to a
solution of (COCl)2 (0.44 mL, 5.04 mmol) in CH2Cl2 (10 mL)
at -78 °C. After stirring for 15 min, a solution of 21 (1.0 g,
2.40 mmol) in CH2Cl2 (10 mL) was added to the reaction
mixture and stirring was continued at the same temperature
for 1 h. Et3N (2.48 mL, 17.8 mmol) was added to the reaction
mixture, which was then gradually warmed to rt and diluted
with CH2Cl2. The organic layer was washed with water and
brine, dried, and concentrated to give the crude aldehyde. To
a stirred solution of phenylacetylene (0.4 mL, 3.64 mmol) in
THF (10 mL) was added a solution of n-BuLi (1.5 M hexane
solution, 2.47 mL, 3.7 mmol) at 0 °C, and the mixture was
stirred for 30 min. A solution of the crude aldehyde in THF
(10 mL) was added to the reaction mixture at the same
temperature. After being stirred for 20 min, the reaction
mixture was quenched with water and extracted with ethyl
acetate. The organic layer was dried and concentrated to leave
22 (992 mg, 80%) consisting of two isomers. The crude 22 was
used without further purification for the next step. A solution
of DMSO (0.68 mL, 9.60 mmol) in CH2Cl2 (3.5 mL) was added
to a solution of (COCl)2 (0.44 mL, 5.04 mmol) in CH2Cl2 (10
mL) at -78 °C. After stirring for 15 min, a solution of 22 (992
mg, 1.92 mmol) in CH2Cl2 (8 mL) was added to the reaction
mixture and the mixture was stirred at the same temperature
for 1 h. Et3N (2.48 mL, 17.8 mmol) was added to the reaction
mixture, which was then gradually warmed to rt and diluted
with CH2Cl2. The organic layer was washed with water and
brine, dried, and concentrated to dryness. The residue was
chromatographed with hexane-ethyl acetate (20:1) to afford
D
0.86, CH2Cl2); lit.2f [R]24 +6.6 (c 0.6, CHCl3)]; MS (FAB) m/z
D
273 (M+ + 1, 78), 207(34), 136 (100), 99 (69), 43 (56); IR 3450,
1785, 1735 cm-1; 1H NMR δ 6.07 (q, 1H, J ) 2.0 Hz), 4.97 (dd,
1H, J ) 2.0, 18.1 Hz), 4.91 (dd, 1H, J ) 2.0, 18.1 Hz), 4.62 (m,
1H), 4.33 (dd, 1H, J ) 5.4, 11.7 Hz), 4.10 (dd, 1H, J ) 6.3,
11.7 Hz), 3.96 (dddd, 1H, J ) 3.4, 5.4, 5.9, 6.3 Hz), 3.20 (d,
1H, J ) 5.9 Hz), 3.04 (d, 1H, J ) 6.4 Hz), 2.36 (t, 2H, J ) 7.3
Hz), 1.61-1.55 (m, 2H), 1.33-1.2 (m, 4H), 0.90 (t, 3H, J ) 6.8
Hz); 13C NMR δ 174.59, 173.46, 169.34, 116.80, 71.68, 71.52,
68.81, 64.76, 34.04, 31.22, 24.49, 22.23, 13.84; HRMS calcd
for C13H21O6 273.1338, found 273.1340
(+)-Syr ibu tin 2 (6). According to the procedure described
for the preparation of (+)-5 from (+)-13, compound (+)-14 (120
mg, 0.35 mmol) in MeOH (7.0 mL) was treated with 5% HCl
(2.0 mL) to give (+)-6 (72.8 mg, 69%) as a colorless oil: [R]17
D
+5.9 (c 0.18, CHCl3); MS m/z 300 (M+, 1.25), 216 (6.3), 140
(34), 127 (100), 114 (70), 57 (88); IR 3400, 1785, 1740 cm-1
;
1H NMR δ 6.05 (q, 1H, J ) 1.7 Hz), 4.98 (dd, 1H, J ) 1.7, 18.1
Hz), 4.89 (dd, 1H, J ) 1.7, 18.1 Hz), 4.63 (m, 1H), 4.27 (dd,
1H, J ) 5.6, 11.5 Hz), 4.16 (dd, 1H, J ) 6.3, 11.5 Hz), 3.96
(dddd, 1H, J ) 3.3, 5.6, 5.9, 6.3 Hz), 3.78 (d, 1H, J ) 6.6 Hz),
3.54 (d, 1H, J ) 5.9 Hz), 2.34 (t, 2H, J ) 7.6 Hz), 1.68-1.51
(m, 2H), 1.38-1.18 (m, 8H), 0.86 (t, 3H, J ) 6.9 Hz); 13C NMR
δ 174.48, 174.23, 170.57, 116.39, 72.04, 71.29, 68.81, 64.55,
34.07, 31.57, 29.00, 28.83, 24.78, 22.54, 14.00; HRMS calcd
for C15H24O6 300.1573, found 300.1581.
(-)-(1′R,2′R)-3-(1′,2′,3′-Tr ih yd r oxyp r op yl)-2-b u t en -4-
olid e (15). To a stirred solution of (-)-11 (125 mg, 0.38 mmol)
in MeOH (2.0 mL) was added 5% HCl (1.0 mL), and the
reaction mixture was stirred at 45 °C for 3 h. Solvent was
evaporated off to leave a residue, which was chromatographed
with CH2Cl2-MeOH (10:1) to provide (-)-15 (59.7 mg, 90%)
(-)-23 (889 mg, 90% from 22) as colorless oil: [R]23 -46 (c
D
0.25, CHCl3); MS m/z 514 (M+, 0.2), 457 (4.8), 349 (44), 319
(42), 129 (100), 91 (99), 75 (54); IR 2220, 1665 cm-1; 1H NMR
δ 7.53-7.18 (m, 15H), 4.92, 4.54 (AB-q, 2H, J ) 11.7 Hz), 4.63
(s, 2H), 4.26 (d, 1H, J ) 2.9 Hz), 4.07 (ddd, 1H, J ) 2.9, 5.9,
7.3 Hz), 3.77 (dd, 1H, J ) 7.3, 10.3 Hz), 3.72 (dd, 1H, J ) 5.9,
10.3 Hz), 0.86 (s, 9H), 0.01 (s, 3H), 0.01 (s, 3H); 13C NMR δ
188.53, 137.90, 137.38, 133.23, 130.84, 128.54, 128.30, 128.19,
127.89, 127.67, 119.89, 94.05, 87.30, 84.49, 80.07, 73.55, 61.53,
25.84, 18.13, -5.44, -5.50; Anal. Calcd for C32H38O4Si: C,
74.67; H, 7.44. Found: C, 74.66; H, 7.58.
as a colorless viscous oil: [R]24.5 -7.9 (c 0.10, MeOH); MS
D
(FAB) m/z 175 (M+ + 1, 13), 154(100), 136 (87), 89 (35), 77
1
(33), 39 (19); IR 3350, 1730 (br) cm-1; H NMR δ 6.09 (t, 1H,
J ) 1.7 Hz), 5.08 (dd, 1H, J ) 2.0, 18.1 Hz), 4.99 (dd, 1H, J )
0.7, 18.1 Hz), 4.83 (br s, 3H), 4.75 (m, 1H), 3.81-3.35 (m, 3H);
13C NMR δ 176.53, 175.27, 116.03, 74.89, 73.69, 70.13, 63.52;
HRMS calcd for C7H11O5 175.0606, found 175.0604
(-)-(1′R,2′R)-3-[1′-(Hexa n oyloxy)-2′,3′-(isop r op ylid en e-
d ioxy)p r op yl]-2-bu ten -4-olid e (17). To a stirred solution
of (-)-15 (110 mg, 0.63 mmol) in THF (5.0 mL) was added
isopropenyl methyl ether (0.07 mL, 0.73 mmol) and a catalytic
amount of p-TSA (1.2 mg, 0.006 mmol) at 0 °C. After stirring
ter t-Bu tyl (-)-(3S,4S,5R)-4,5-Bis(ben zyloxy)-6-[(ter t-bu -
t yld im et h ylsilyl)oxy]-3-h yd r oxy-3-(p h en ylet h yn yl)h ex-
a n eth ioa te (24). To a stirred solution of tert-butyl thioacetate

Synthesis of Secosyrins and Syributins
J . Org. Chem., Vol. 62, No. 23, 1997 8101
(15.8 mg, 0.12 mmol) in THF (1.0 mL) at -78 °C was added a
solution of LHMDS (1.0 M THF solution, 0.12 mL, 0.12 mmol).
After stirring at -78 °C for 30 min, a solution of (-)-23 (51.4
mg, 0.10 mmol) in THF (1.0 mL) was added dropwise to a
solution of the enolate in THF. The reaction mixture was
stirred for 30 min, quenched with water, and extracted with
ethyl acetate. The organic layer was washed with water, dried,
and concentrated to dryness. The residue was chromato-
graphed with hexane-ethyl acetate (20:1) to afford (-)-24 (60.7
mg, 94%) as colorless solids: mp 48-49 °C (hexane-ether);
6.61 (d, 1H, J ) 13.2 Hz), 5.89 (d, 1H, J ) 13.2 Hz), 4.69 (s,
2H), 4.43, 4.38 (AB-q, 2H, J ) 11.9 Hz), 4.24 (d, 1H, J ) 3.6
Hz), 4.05 (ddd, 1H, J ) 3.6, 4.3, 5.6 Hz), 3.63 (dd, 1H, J )
5.6,8.6 Hz), 3.58 (dd, 1H, J ) 4.3, 8.6 Hz), 2.99, 2.89 (AB-q,
2H, J ) 14.5 Hz), 1.43 (s, 9H); 13C NMR δ 196.78, 138.15,
137.77, 137.27, 131.34, 129.34, 128.90, 128.39, 128.34, 127.76,
127.71, 127.66, 127.39, 126.72, 87.35, 84.31, 83.06, 72.74,
71.83, 69.24, 51.36, 48.20, 29.65. Anal. Calcd for C32H36O4S:
C, 74.39; H, 7.02. Found: C, 74.36; H, 7.13.
ter t-Bu tyl (+)-(3S,4S,5R)-4,5-Bis(ben zyloxy)-3,6-d ih y-
d r oxy-3-((Z)-2′-p h en yleth en yl)h exa n eth ioa te (28). Ac-
cording to the procedure described for conversion of 26 into
27, compound (-)-25 (148 mg, 0.28 mmol) was partially
hydrogenated in the presence of Lindlar catalyst to give (+)-
28 (111.4 mg, 78%) as a colorless oil: [R]24D +2.74 (c 0.23,
CHCl3); MS (FAB) m/z 535 (M+ + 1, 0.4), 401 (1), 207 (8), 181
(14), 131(41), 91 (100), 57 (42); IR 3450, 1660 cm-1; 1H NMR δ
7.40-7.15 (m, 15H), 6.60 (d, 1H, J ) 13.2 Hz), 5.72 (d, 1H, J
) 13.2 Hz), 4.89, 4.70 (AB-q, 2H, J ) 11.2 Hz), 4.65 (s, 2H),
3.91 (s, 1H), 3.79-3.57 (m, 4H), 3.15, 2.90 (AB-q, 2H, J ) 15.5
Hz), 2.33 (t, 1H, J ) 6.6 Hz), 1.46 (s, 9H); 13C NMR δ 201.45,
138.15, 138.10, 137.29, 131.72, 131.52, 128.91, 128.43, 128.39,
128.36, 128.16, 127.80, 127.75, 127.69, 126.85, 83.16, 80.25,
79.35, 75.08, 72.78, 62.59, 50.95, 48.74, 29.69. Anal. Calcd for
C32H38O5S: C, 71.88; H, 7.16. Found: C, 71.60; H, 7.20.
Con ver sion of (+)-28 in to (-)-27. According to the
procedure described for transformation of 25 into 26, com-
pound 28 (106 mh, 0.20 mmol) in CH2Cl2 (5.0 mL) was treated
with Et3N (0.04 mL, 0.28 mm0l), DMAP (34.2 mg, 0.28 mmol),
and p-TsCl (53.4 mg, 0.28 mmol) to afford (-)-27 (90 mg, 88%).
(+)-(3R,4S,5S)-3,4-Bis(ben zyloxy)-1,7-d ioxa sp ir o[4.4]-
n on a n -8-on e (29).17 Ozone was passed through a solution of
(-)-27 (135 mg, 0.26 mmol) and pyridine (0.026 mL, 0.35
mmol) in CH2Cl2 (6.5 mL) at -78 °C until a pale blue color
persisted (15 min). Excess ozone was removed by bubbling
oxygen through the solution until the reaction was maintained
a clear color (5 min). Excess methyl sulfide (0.09 mL, 1.3
mmol) was added at -78 °C, and the reaction mixture was
gradually warmed to rt. The solvents were removed, and the
crude product was passed through a short pad of silica gel with
hexane-ethyl acetate (10:3) to afford the crude aldehyde. To
a solution of the crude aldehyde in MeOH (5.0 mL) was added
NaBH4 (14.7 mg, 0.39 mmol) portionwise at 0 °C. The reaction
mixture was stirred at rt for 20 min, and MeOH was
evaporated off. The residue was taken up in CH2Cl2, which
was washed with water, dried, and concentrated to dryness.
The residue was dissolved in CH2Cl2 (6.5 mL), to which a
catalytic amount of DBU (3.9 mg, 0.026 mmol) was added. The
reaction mixture was stirred at rt for 30 min, and washed with
water and brine, dried, and concentrated to dryness. Chro-
matography of the residue with hexane-ethyl acetate (5:1)
afforded (+)-29 (66.7 mg, 72%) as colorless crystals: mp 93-
[R]22 -80.5 (c 0.50, CHCl3); MS m/z 646 (M+, 2.2), 547 (21),
D
305 (21), 199 (28), 153 (100), 89 (39), 46 (48); IR 3450, 1655
1
cm-1; H NMR δ 7.43-7.12 (m, 15H), 4.97 (s, 1H), 4.93, 4.76
(AB-q, 2H, J ) 11.2 Hz), 4.72, 4.65 (AB-q, 2H, J ) 11.2 Hz),
4.13 (ddd, 1H, J ) 2.9, 5.9, 6.4 Hz), 3.90 (d, 1H, J ) 2.9 Hz),
3.73 (dd, 1H, J ) 5.9, 10.3 Hz), 3.65 (dd, 1H, J ) 6.4, 10.3
Hz), 3.43, 3.07 (AB-q, 2H, J ) 15.6 Hz), 1.48 (s, 9H), 0.87 (s,
9H), 0.01 (s, 3H), 0.01 (s, 3H); 13C NMR δ 202.42, 138.38,
138.17, 131.68, 128.61, 128.45, 128.30, 128.21, 127.64, 127.58,
122.57, 89.35, 86.43, 82.55, 80.76, 75.56, 74.00, 63.20,
50.37, 48.54, 29.65, 25.90, 18.17, -5.37, -5.42. Anal. Calcd
for C38H50O5SSi: C, 70.55; H, 7.79. Found: C, 70.38; H, 7.86.
ter t-Bu tyl (-)-(3S,4S,5R)-4,5-Bis(ben zyloxy)-3,6-d ih y-
d r oxy-3-(p h en yleth yn yl)h exa n eth ioa te (25). A solution of
TBAF and hydrofluoric acid (0.25 mL, prepared from 0.23 mL
of 1.0 M TBAF in THF solution and 0.02 mL of 47% hydrof-
luoric acid) was added to a solution of (-)-24 (142 mg, 0.22
mmol) in THF at rt. After consumption of the starting
material (monitered by TLC), the reaction mixture was diluted
with water and extracted with ethyl acetate. The organic layer
was washed with water, dried, and concentrated to dryness.
The residue was chromatographed with hexane-ethyl acetate
(10:2) to afford (-)-25 (111 mg, 95%) as a colorless oil: [R]25
D
-126 (c 0.30 CHCl3); MS m/z 532 (M+, 0.2), 367 (8.5), 205 (34),
129 (100), 91 (99), 57 (73); IR 3450, 2200, 1660 cm-1; 1H NMR
δ 7.46-7.21 (m, 15H), 4.97 (s, 1H), 4.90, 4.84 (AB-q, 2H, J )
11.2 Hz), 4.67 (s, 2H), 4.07 (dt, 1H, J ) 4.6, 9.2 Hz), 3.81-
3.78 (m, 3H), 3.41, 2.94 (AB-q, 2H, J ) 15.5 Hz), 1.48 (s, 9H);
13C NMR δ 202.12, 137.99, 137.79, 131.72, 128.61, 128.57,
128.46, 128.41, 128.34, 128.23, 128.07, 127.96, 127.75, 122.28,
88.52, 86.54, 82.77, 80.52, 75.17, 73.37, 73.23, 62.25, 50.62,
48.82, 29.63. Anal. Calcd for C32H36O5S: C, 72.15; H, 6.81.
Found: C, 71.90; H, 6.91.
(-)-(2S,3S,4R)-3,4-Bis(b en zyloxy)-2-[[(ter t-b u t ylt h io)-
car bon yl]m eth yl]-2-(ph en yleth yn yl)tetr ah ydr ofu r an (26).
To a stirred solution of (-)-25 (53.2 mg, 0.10 mmol), Et3N (0.02
mL, 0.14 mmol), and DMAP (17.1 mg, 1.4 mmol) in CH2Cl2
(2.0 mL) was added TsCl (26.7 mg, 0.14 mmol) portionwise at
0 °C. The reaction mixture was warmed to rt and stirring was
continued for 3 h. The mixture was diluted with water and
extracted with CH2Cl2, which was washed with water, dried,
and concentrated to dryness. The residue was chromato-
graphed with hexane-ethyl acetate (20:1) to afford (-)-26 (45.8
94 °C (hexane-ether); [R]22 +44.7 (c 0.51, CHCl3); MS m/z
D
mg, 89%) as a colorless oil: [R]19 -64.3 (c 0.52, CHCl3); MS
D
354 (M+, 0.81), 294 (1.2), 263 (100), 157 (40), 91 (92), 65 (55);
IR 1780 cm-1; 1H NMR δ 7.40-7.25 (m, 10H), 4.63, 4.31 (AB-
q, 2H, J ) 10.3 Hz), 4.57, 4.47 (AB-q, 2H, J ) 11.7 Hz), 4.51,
4.49 (AB-q, 2H, J ) 10.7 Hz), 4.14-4.1 (m, 2H), 3.97-3.94
(m, 2H), 2.72, 2.62 (AB-q, 2H, J ) 18.1 Hz); 13C NMR δ 175.13,
137.20, 136.91, 128.64, 128.61, 128.27, 128.09, 127.73, 127.58,
86.83, 85.19, 81.44, 73.30, 72.18, 71.70, 71.38, 39.64. Anal.
Calcd for C21H22O5: C, 71.17; H, 6.26. Found: C, 71.00; H,
6.26.
(FAB) m/z 515 (M+ + 1, 1.1), 459 (5.6), 247 (8.6), 181 (8.0), 91
1
(100), 57 (63); IR 2225, 1675 cm-1; H NMR δ 7.46-7.25 (m,
15H), 4.87, 4.70 (AB-q, 2H, J ) 11.7 Hz), 4.50, 4.43 (AB-q,
2H, J ) 11.7 Hz), 4.42 (d, 1H, J ) 1.5 Hz), 4.21 (dd, 1H, J )
4.9, 9.8 Hz), 4.17 (ddd, 1H, J ) 1.5, 2.0, 4.9 Hz), 3.92 (dd, 1H,
J ) 2.0, 9.8 Hz), 3.13, 3.05 (AB-q, 2H, J ) 14.2 Hz), 1.45 (s,
9H); 13C NMR δ 196.06, 138.08, 137.59, 131.90, 128.45, 128.37,
128.30, 128.09, 127.87, 127.82, 127.76, 127.66, 122.70, 88.27,
86.15, 84.04, 80.67, 72.72, 71.56, 70.77, 52.33, 48.34, 29.65.
Anal. Calcd for C32H34O4S: C, 74.68; H, 6.66. Found: C, 74.52;
H, 6.72.
(+)-(3R,4S,5S)-3,4-Dih ydr oxy-1,7-dioxaspir o[4.4]n on an -
8-on e (30). A solution of (+)-29 (120 mg, 0.34 mmol) in ethyl
acetate (7.0 mL) and MeOH (0.1 mL) in the presence of one
drop of 10% hydrochloric acid was hydrogenated over 10%
Pd-C (12 mg) under a hydrogen atmosphere for 3 h at rt. The
catalyst was filtered off and the filtrate was concentrated to
dryness. The residual solids were recrystallized from hexane-
ethyl acetate to provide (+)-30 (55.4 mg, 94%) as colorless
needels: mp 140-141 °C; [R]23D +13.0 (c 0.39, MeOH); MS m/z
(-)-(2S,3S,4R)-3,4-Bis(b en zyloxy)-2-[[(ter t-b u t ylt h io)-
ca r bon yl]m eth yl]-2-((Z)-2′-p h en yleth en yl)tetr a h yd r ofu -
r a n (27). A solution of (-)-26 (180 mg, 0.35 mmol) in ethyl
acetate (15 mL) was hydrogenated under a hydrogen atmo-
sphere in the presence of Lindlar catalyst (20 mg) at rt for 48
h. The catalyst was filtered off and the filtrate was concen-
trated to dryness. Chromatography of the residue with
hexane-ethyl acetate (20:1) gave (-)-27 (136 mg, 75%) as a
(17) The atomic coordinates for this structure have been deposited
with the Cambridge Crystallographic Data Centre. The coordinates
can be obtained, on request, from the Director, Cambridge Crystal-
lographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, UK.
colorless oil: [R]22 -26.4 (c 0.49, CHCl3); MS m/z 516 (M+,
D
0.1), 460 (7), 385 (25), 276(30), 203 (38), 131(72), 128(32), 91
1
(92), 57 (100); IR 1680 cm-1; H NMR δ 7.48-7.15 (m, 15H),

8102 J . Org. Chem., Vol. 62, No. 23, 1997
Mukai et al.
174 (M+, 1.1), 156 (17), 116 (88), 101 (26), 74 (100), 56 (82); IR
afforded (+)-34 (60.5 mg, 74%) as a colorless oil along with
(-)-26 (12.3 mg, 15%). Compound (+)-34: [R]23D +92.8 (c 0.30,
CHCl3); MS m/z 514 (M+, 0.3), 457 (44), 367 (44), 349 (57),
1
3350, 3475, 1775 cm-1; H NMR δ 4.88 (br s, 2H), 4.63, 4.28
(AB-q, 2H, J ) 10.2 Hz), 4.21-4.15 (m, 2H), 4.11 (br s, 1H),
3.81 (dt, 1H, J ) 3.3, 4.6 Hz), 2.98, 2.66 (AB-q, 2H, J ) 17.8
Hz); 13C NMR δ 178.65, 89.16, 81.58, 78.42, 75.59, 74.68, 40.64.
Anal. Calcd for C7H10O5: C, 48.28; H, 5.79. Found: C, 48.13;
H, 5.76.
1
244 (22), 129 (36), 91 (99), 57 (100),; IR 2225, 1685 cm-1; H
NMR δ 7.41-7.23 (m, 15H), 4.69, 4.60 (AB-q, 2H, J ) 11.7
Hz), 4.58, 4.45 (AB-q, 2H, J ) 11.7 Hz), 4.43 (d, 1H, J ) 2.0
Hz), 4.24 (dd, 1H, J ) 6.4, 9.8 Hz), 4.12 (ddd, 1H, J ) 2.0, 3.9,
6.4 Hz), 4.00 (dd, 1H, J ) 3.9, 9.8 Hz), 3.26, 3.14 (AB-q, 2H, J
) 15.1 Hz), 1.46 (s, 9H); 13C NMR δ 196.05, 137.81, 137.61,
131.84, 128.37, 128.32, 128.27, 128.03, 127.92, 127.85, 127.64,
127.53, 122.66, 87.87, 87.51, 86.70, 83.18, 78.94, 72.53, 71.52,
71.02, 49.18, 48.12, 29.76. Anal. Calcd for C32H34O4S: C,
74.68; H, 6.66. Found: C, 74.68; H, 6.70.
(+)-(3 R ,4 S ,5 S )-4 -(H e x a n o y l o x y )-3 -h y d r o x y -1 ,7 -
d ioxa sp ir o[4.4]n on a n -8-on e (31) [(+)-5-Ep isecosyr in 1]
a n d (-)-(3R,4S,5S)-3,4-Bis(h exa n oyloxy)-1,7-d ioxa sp ir o-
[4.4]n on a n -8-on e (32). A solution of hexanoic anhydride (0.1
M THF solution, 2.3 mL, 0.23 mmol) was added to a solution
of (+)-30 (40 mg, 0.23 mmol), Et3N (0.03 mL, 0.23 mmol), and
DMAP (3.0 mg, 0.024 mmol) in THF (3.0 mL) at 0 °C. After
stirring for 1 h, the reaction mixture was diluted with
saturated NaHCO3 solution and extracted with ether, which
was washed with water and brine, dried, and concentrated to
dryness. Chromatography of the residue with hexane-ethyl
acetate (20:1) gave (+)-31 (43.8 mg, 70%) as a colorless oil.
Further elution with hexane-ethyl acetate (2:1) afforded (-)-
32 (17 mg, 20%) as a colorless oil. (+)-5-Episecosyrin 1 (31):
(+)-(2R,3S,4R)-3,4-Bis(ben zyloxy)-2-[[(ter t-bu tylth io)-
ca r bon yl]m eth yl]-2-((Z)-2′-p h en yleth en yl)tetr a h yd r ofu -
r a n (35). According to the procedure described for the
preparation of 27 from 26, compound (+)-34 (230 mg, 0.48
mmol) in ethyl acetate (20 mL) was hydrogenated over Lindlar
catalyst (25 mg) to provide (+)-35 (180 mg, 78%) as a colorless
oil: [R]19
+27.3 (c 0.51, CHCl3); MS m/z 516 (M+, 0.2), 460
D
(27), 352 (21), 203 (35), 131 (63), 91 (95), 57 (100); IR 1680
cm-1 1H NMR δ 7.42-7.14 (m, 15H), 6.55 (d, 1H, J ) 12.7
;
[R]26 +33.6 (c 0.12, CHCl3); MS m/z 272 (M+, 4.9), 230 (9.4),
D
216 (17), 167 (25), 149 (61), 99 (100); IR 3450, 1780, 1735 cm-1
;
Hz), 5.89 (d, 1H, J ) 12.7 Hz), 4.45, 4.38 (AB-q, 2H, J ) 12.2
Hz), 4.40 (s, 2H), 4.15 (d, 1H, J ) 2.0 Hz), 4.00-3.99 (m, 2H),
3.59 (ddd, 1H, J ) 2.0, 2.4, 5.9 Hz), 3.16, 3.12 (AB-q, 2H, J )
1H NMR δ 5.03 (d, 1H, J ) 1.7 Hz), 4.37, 4.32 (AB-q, 2H, J )
10.2 Hz), 4.31 (ddd, 1H, J ) 1.7, 2.6, 5.3 Hz), 4.17 (dd, 1H, J
) 5.3, 10.2 Hz), 3.83 (dd, 1H, J ) 2.6, 10.2 Hz), 2.86, 2.75 (AB-
q, 2H, J ) 18.5 Hz), 2.36 (t, 2H, J ) 7.6 Hz), 1.72-1.55 (m,
2H), 1.42-1.22 (m, 4H), 0.90 (t, 3H, J ) 6.9 Hz); 13C NMR δ
174.59, 173.48, 85.86, 82.97, 76.01, 72.87,72.81, 39.36, 33.98,
31.16, 24.46, 22.19, 13.82; HRMS calcd for C13H20O6 273.1260,
15.6 Hz), 1.42 (s, 9H);
13C NMR δ 197.34, 137.86, 137.04,
133.23, 130.91, 129.31, 128.39, 128.27, 127.80, 127.69, 127.62,
127.57, 127.51, 126.90, 87.76, 85.16, 83.00, 72.06, 71.47, 70.14,
49.71, 47.93, 29.76. Anal. Calcd for C32
7.02. Found: C, 74.24; H, 7.12.
H36O4S: C, 74.39; H,
found 272.1256. Diester (-)-32: [R]25 -15.6 (c 0.12, CHCl3);
(+)-(3R,4S,5R)-3,4-Bis(ben zyloxy)-1,7-d ioxa sp ir o[4.4]-
n on a n -8-on e (36). According to the procedure described for
the preparation of 29 from 27, compound (+)-35 (103 mg, 0.2
mmol) was treated successively with ozone, NaBH4, and DBU
to afford (+)-36 (53.1 mg, 75%) as colorless needles: mp 64.5-
65.5 °C (hexane-ether); [R]23D +34.0 (c 0.22, CHCl3); MS m/z
354 (M+, 0.99), 263 (100), 157 (37), 91 (97), 65 (51); IR 1785
D
MS m/z 370 (M+, 1.7), 314 (8.3), 212 (29), 171 (32), 99 (100),
1
71 (47); IR 1790, 1745 cm-1; H NMR δ 5.32 (d, 1H, J ) 1.5
Hz), 5.15 (ddd, 1H, J ) 1.5, 2.0, 4.9 Hz), 4.33, 4.31 (AB-q, 2H,
J ) 10.7 Hz), 4.28 (dd, 1H, J ) 4.9, 10.7 Hz), 3.86 (dd, 1H, J
) 2.0, 10.7 Hz), 2.80, 2.74 (AB-q, 2H, J ) 17.6 Hz), 2.37 (t,
2H, J ) 7.3 Hz), 2.35 (t, 2H, J ) 7.3 Hz), 1.71-1.55 (m, 4H),
1.42-1.22 (m, 8H), 0.91 (t, 6H, J ) 6.8 Hz); 13C NMR δ 173.96,
172.42, 172.25, 86.34, 79.00, 72.58, 71.66, 39.10, 33.96, 33.86,
31.14, 24.42, 22.19, 13.82. Anal. Calcd for C19H30O7: C, 61.60;
H, 8.16. Found: C, 61.31; H, 8.28.
1
cm-1; H NMR δ 7.43-7.22 (m, 10H), 4.66, 4.46 (AB-q, 2H, J
) 11.9 Hz), 4.54, 4.50 (AB-q, 2H, J ) 9.6 Hz), 4.31, 4.21 (AB-
q, 2H, J ) 10.2 Hz), 4.12 (ddd, 1H, J ) 2.0, 2.3, 4.6 Hz), 4.05
(dd, 1H, J ) 4.6, 9.9 Hz), 3.92 (dd, 1H, J ) 2.3, 9.9 Hz), 3.87
(d, 1H, J ) 2.0 Hz), 2.96, 2.56 (AB-q, 2H, J ) 8.5 Hz); 13C
NMR δ 175.51, 137.63, 137.43, 129.13, 128.73, 128.61, 128.23,
128.14, 87.73, 84.62, 82.12, 76.52, 72.85, 72.29, 71.36, 35.56.
Anal. Calcd for C21H22O5: C, 71.17; H, 6.26. Found: C, 70.97;
H, 6.25.
H exa ca r b on yl-µ-[η4-ter t-b u t yl (-)-(3S,4S,5R)-4,5-b is-
(ben zyloxy)-3,6-d ih yd r oxy-3-(p h en yleth yn yl)h exa n eth -
ioa te]d icoba lt (Co-Co) (33). A solution of (-)-25 (90 mg,
0.17 mmol) in ether (1.5 mL) was added dropwise to a stirred
solution of octacarbonyldicobalt (68.4 mg, 0.2 mmol) in ether
(3.0 mL). The reaction mixture was stirred at rt for 4 h and
then ether was evaporated off. The residue was chromato-
graphed with hexane-ethyl acetate (20:1) to afford 33 (136
mg, 98%) as a deep brown oil: MS (FAB) m/z 819 (M+ + 1,
0.1), 331 (34), 171 (100), 153 (23), 46 (8.5); IR 3400, 2075, 2025,
1995, 1650 cm-1; 1H NMR δ 7.54-7.16 (m, 15H), 5.46 (s, 1H),
4.95, 4.65 (AB-q, 2H, J ) 9.9 Hz), 4.30 (s, 2H), 4.00 (d, 1H, J
) 7.6 Hz), 3.82-3.66 (m, 3H), 3.69, 2.99 (AB-q, 2H, J ) 6.2
Hz), 2.00 (t, 1H, J ) 5.3 Hz), 1.48 (s, 9H); 13C NMR δ 203.04,
199.35, 138.65, 138.40, 137.93, 129.58, 128.99, 128.66, 128.34,
128.21, 127.67, 82.88, 81.12, 79.61, 76.39, 72.22, 62.59, 52.17,
49.44, 29.69. Anal. Calcd for C38H36Co2O11S: C, 55.75; H, 4.43.
Found: C, 55.91; H, 4.47. Specific rotation could not be
determined because demetalation occurred during measure-
ment.
(+)-(2R,3S,4R)-3,4-Bis(ben zyloxy)-2-[[(ter t-bu tylth io)-
car bon yl]m eth yl]-2-(ph en yleth yn yl)tetr ah ydr ofu r an (34).
To a solution of 33 (130 mg, 0.16 mmol) in CH2Cl2 (4.0 mL)
was added BF3‚Et2O (0.1 M CH2Cl2 solution, 1.7 mL, 0.17
mmol) at rt, and the reaction mixture was stirred for 3 h. The
mixture was quenched with water and extracted with CH2-
Cl2. The organic layer was washed with water and brine,
dried, and concentrated to give the cobalt-complexed residue,
which was dissolved in MeOH (5.0 mL). To a solution of
cobalt-complexed 34 and 26 in MeOH was added CAN (351
mg, 0.64 mmol) at 0 °C, and the reaction mixture was stirred
for 25 min at the same temperature. MeOH was evaporated
off and the residue was taken up in ethyl acetate, which was
washed with water, dried, and concentrated to dryness.
Chromatography of the residue with hexane-ether (10:1)
(+)-(3R,4S,5R)-3,4-Dih ydr oxy-1,7-dioxaspir o[4.4]n on an -
8-on e (37). According to the procedure described for the
preparation of 30 from 29, compound (+)-36 (180.5 mg, 0.51
mmol) was hydrogenolyzed over 10% Pd/C catalyst (18 mg)
under hydrogen atmosphere at rt to provide (+)-37 (79.8 mg,
90%) as colorless needels: mp 107-108 °C (hexane-ethyl
acetate); [R]25
+75.3 (c 0.22, MeOH); MS m/z 174 (M+, 0.55),
D
170 (0.3), 156 (15), 116 (100), 74 (82), 56 (68); IR 3350, 3475,
1
1775 cm-1; H NMR δ 4.86 (br s, 2H), 4.42, 4.37 (AB-q, 2H, J
) 10.2 Hz), 4.22-4.09 (m, 1H), 4.15 (dd, 1H, J ) 4.6, 8.9 Hz),
4.00 (d, 1H, J ) 2.0 Hz), 3.79 (dd, 1H, J ) 1.3, 8.9 Hz), 3.06,
2.47 (AB-q, 2H, J ) 18.1 Hz); 13C NMR δ 178.23, 89.83, 80.28,
78.09, 77.95, 74.16, 36.37. Anal. Calcd for C7H10O5: C, 48.28;
H, 5.79. Found: C, 48.22; H, 5.83.
(+)-(3 R ,4 S ,5 R )-4 -(H e x a n o y l o x y )-3 -h y d r o x y -1 ,7 -
d ioxa sp ir o[4.4]n on a n -8-on e (3) (Secosyr in 1) a n d (-)-
(3R,4S,5R)-3,4-Bis(h exan oyloxy)-1,7-dioxaspir o[4.4]n on an -
8-on e (38). According to the procedure described for the
preparation of 31 from 30, compound (+)-37 (50.5 mg, 0.29
mmol) was treated with hexanoic anhydride (0.1 M THF
solution, 2.87 mL, 0.29 mmol), Et3N (0.04 mL, 0.29 mmol), and
DMAP (3.7 mg, 0.03 mmol) in THF (3.0 mL) at 0 °C to give
(+)-secosyrin 1 (3) (55.3 mg, 70%) as a colorless oil along with
(-)-38 (26.8 mg, 25%) as a colorless oil. (+)-Secosyrin 1 (3):
[R]26 +48.2 (c 0.12, CHCl3) [lit.10 [R]D +42.85 (c 1.43, CH2-
D
Cl2)]; MS m/z 272 (M+, 12), 158 (39), 128 (39), 99 (99), 98 (75),
1
71 (100); IR 3500, 1785, 1735 cm-1; H NMR δ 4.96 (d, 1H, J
) 2.0 Hz), 4.45, 4.37 (AB-q, 2H, J ) 10.2 Hz), 4.32 (ddd, 1H,
J ) 2.0, 2.7, 5.3 Hz), 4.13 (dd, 1H, J ) 5.3, 10.2 Hz), 3.86 (dd,
1H, J ) 2.7, 10.2 Hz), 2.78, 2.58 (AB-q, 2H, J ) 17.8 Hz), 2.37

Synthesis of Secosyrins and Syributins
J . Org. Chem., Vol. 62, No. 23, 1997 8103
(t, 2H, J ) 7.6 Hz), 1.71-1.54 (m, 2H), 1.41-1.22 (m, 4H),
0.89 (t, 3H, J ) 6.9 Hz); 13C NMR δ 174.57, 173.53, 86.63,
81.47, 75.94, 75.55, 72.90, 35.47, 33.96, 31.09, 24.40, 22.12,
13.75; HRMS calcd for C13H20O6 273.1260, found 272.1249.
Diester (-)-38: [R]25D -14.0 (c 0.13, CHCl3); MS m/z 370 (M+,
4.8), 314 (13), 212 (60), 171 (89), 99 (100), 71 (98); IR 1790,
300.1573, found 300.1573. Diester (-)-39: [R]22D -15.1 (c 0.07,
CHCl3); MS m/z 426 (M+, 5.0), 342(10), 301 (22), 240 (30), 199
1
(38), 127 (100), 57 (85); IR 1790, 1740 cm-1; H NMR δ 5.27
(d, 1H, J ) 2.0 Hz), 5.18 (ddd, 1H, J ) 2.0, 2.3, 5.0 Hz), 4.38
(s, 2H), 4.24 (dd, 1H, J ) 5.0, 10.9 Hz), 3.88 (dd, 1H, J ) 2.3,
10.9 Hz), 2.73, 2.59 (AB-q, 2H, J ) 17.8 Hz), 2.38 (t, 2H, J )
7.6 Hz), 2.34 (t, 2H, J ) 7.6 Hz), 1.72-1.55 (m, 4H), 1.42-
1.19 (m, 16H), 0.89 (t, 6H, J ) 6.9 Hz); 13C NMR δ 173.69,
172.42, 87.10, 77.77, 76.91, 75.22, 71.29, 35.26, 33.98, 33.95,-
33.91, 31.52,28.99, 28.86, 28.81, 24.76, 24.71, 24.66, 22.54,
14.00. Anal. Calcd for C23H38O7: C, 64.76; H, 8.98. Found:
C, 64.47; H, 9.12.
1
1745 cm-1; H NMR δ 5.27 (d, 1H, J ) 2.0 Hz), 5.16 (dt, 1H,
J ) 4.9, 2.0 Hz), 4.38, 4.34 (AB-q, 2H, J ) 10.6 Hz), 4.22 (dd,
1H, J ) 4.9, 10.9 Hz), 3.86 (dd, 1H, J ) 2.0, 10.9 Hz), 2.72,
2.57 (AB-q, 2H, J ) 17.8 Hz), 2.37 (t, 2H, J ) 7.6 Hz), 2.33 (t,
2H, J ) 7.6), 1.72-1.56 (m, 4H), 1.42-1.22 (m, 8H), 0.89 (t,
6H, J ) 6.9 Hz); 13C NMR δ 173.66, 172.40, 87.08, 77.74, 76.87,
75.19, 71.27, 35.22, 33.91, 33.87, 31.13, 24.40, 24.37, 22.18,
13.80. Anal. Calcd for C19H30O7: C, 61.60; H, 8.16. Found:
C, 61.41; H, 8.24.
Ack n ow led gm en t. The authors wish to thank Pro-
fessor J ames J . Sims, University of California, River-
side, for providing the specific rotation data of secosyrin
1 and syributin 1. The authors are grateful to Dr. S.
Hosoi for X-ray crystallographic analysis. This work was
supported in part by Grant-in-Aid for Scientific Re-
search from the Ministry of Education, Science and
Culture of J apan, to which the authors’ thanks are due.
(+)-(3 R ,4 S ,5 R )-3 -H y d r o x y -4 -(o c t a n o y l o x y )-1 ,7 -
d ioxa sp ir o[4.4]n on a n -8-on e (4) (Secosyr in 2) a n d (-)-
(3R,4S,5R)-3,4-Bis(octan oyloxy)-1,7-dioxaspir o[4.4]n on an -
8-on e (39). According to the procedure described for the
preparation of 31 from 30, compound (+)-37 (35 mg, 0.2 mmol)
was treated with octanoic anhydride (0.2 mmol) to give
secosyrin 2 (4) (47.1 mg, 78%) as a colorless oil along with (-)-
39 (12.9 mg, 15%) as a colorless oil. (+)-Secosyrin 2 (4): [R]21
D
+40.5 (c 0.10, CHCl3); MS m/z 300 (M+, 12), 216 (18), 156 (20),
127 (100), 98 (35), 57 (78); IR 3500, 1785, 1735 cm-1; 1H NMR
δ 4.94 (d, 1H, J ) 2.0 Hz), 4.46, 4.37 (AB-q, 2H, J ) 10.2 Hz),
4.33 (ddd, 1H, J ) 2.0, 3.0, 5.3 Hz), 4.14 (dd, 1H, J ) 5.3, 10.2
Hz), 3.86 (dd, 1H, J ) 3.0, 10.2 Hz), 2.79, 2.59 (AB-q, 2H, J )
18.1 Hz), 2.38 (t, 2H, J ) 7.6 Hz), 1.68-1.60 (m, 2H), 1.38-
1.27 (m, 8H), 0.89 (t, 3H, J ) 6.9 Hz); 13C NMR δ 174.16,
173.73, 86.56, 81.98, 75.89, 75.67, 72.63, 35.40, 34.07, 31.57,
29.00, 28.81, 24.82, 22.55, 14.00; HRMS calcd for C15H24O6
Su p p or t in g In for m a t ion Ava ila b le: 13C and 1H NMR
spectra for compounds (+)-3-6 and (-)-15 (10 pages). This
material is contained in libraries on microfiche, immediately
follows this article in the microform version of the journal, and
can be ordered from the ACS; see any current masthead page
for ordering information.
J O9711089