Total Synthesis of Allocyathin B2, a Metabolite of Bird's Nest Fungi

Article abstract of DOI:10.1021/jo971514s

Allocyathin B₂ has been synthesized using aldol reactions for construction of rings A and B, introduction of the side chain for ring B, cyclization of the acetyl group into a lactone, and construction of the seven-membered diene aldehyde during the last step.

Full text of DOI:10.1021/jo971514s

306
J . Org. Chem. 1998, 63, 306-313
Tota l Syn th esis of Allocya th in B2, a Meta bolite of Bir d ’s Nest
F u n gi
Motoo Tori,* Naoko Toyoda, and Masakazu Sono
Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima 770, J apan
Received August 13, 1997
Allocyathin B2 has been synthesized using aldol reactions for construction of rings A and B,
introduction of the side chain for ring B, cyclization of the acetyl group into a lactone, and
construction of the seven-membered diene aldehyde during the last step.
Sch em e 1
In tr od u ction
The fruit bodies of Cyathus earlei are small and they
look like a tiny “bird’s nest”.1e The metabolites of this
fungi have been found by Ayer and co-workers to have
cyathane diterpene skeletons successively consisting of
five-, six-, and seven-membered rings, to constitute one
of the most unusual terpenoid frameworks thus far
discovered.1,2 This kind of terpenoid has also been found
in other mushrooms studied by Shibata et al.3 and
Kawagishi et al.4 and in liverworts by Asakawa and his
group.5 Although there has been considerable effort to
synthesize these molecules,6 only recently has Snider
succeeded in the total synthesis of allocyathin B2 (1) as
well as its xyloside, erinacine A (2).7 We have been
interested in structurally unusual natural products as
well as biologically active compounds. Kawagishi re-
ported the isolation and structure elucidation of erinacine
A (2) and its congeners, which show strong nerve-growth-
inducing activities.4 We have started our synthetic work
as outlined in Scheme 1, during which time Snider
reported the first total synthesis of both allocyathin B2
(1) and erinacine A (2).7 This synthetic plan has three
unique features: (1) the stereochemistry at the C-11
position can be controlled by the order of the alkylation
reaction, (2) introduction of the two-carbon unit for C-6
and C-7 can be accomplished by the intramolecular aldol
cyclization, which is difficult because of the hindered
nature at the C-5 position, and (3) the E arrangement of
the C-5 and C-6 double bond is advantageous for in-
tramolecular aldol cyclization in the last step.
Resu lts a n d Discu ssion
Con str u ction of Rin gs A a n d B. The 1,4-addition
of the Grignard reagent of 4-bromo-1-butene to 3-methyl-
2-cyclohexen-1-one (3) in the presence of CuBr‚Me2S
followed by ketalization afforded 5. Ozonolysis and
alkylation with isopropylmagnesium bromide afforded
the alcohol 6, which was subjected to J ones oxidation to
give the diketone 7, with concomitant deprotection of the
ketal group. Finally, base-catalyzed aldol cyclization
gives the desired bicyclic enone 8 in high yield (Scheme
2).
P r ep a r a tion of th e F ou r -Ca r bon Sid e Ch a in . We
have prepared two types of aldehydes, 11 and 14, and
acid chloride 16 as outlined in Scheme 3. γ-Butyrolac-
tone (9) was hydrolyzed, methylated, and protected to
give the methyl ester 10, which was converted to the
aldehyde 11 in high yield. The silyl-protected aldehyde
14 was prepared from butane-1,4-diol (12) in two steps.
The acid chloride 16 was prepared from 12 through
alcohol 15, as previously described.8
* Phone, +81-886-22-9611, ext. 5631; fax +81-886-55-3051; e-mail,
tori@mxs.meshnet.or.jp.
(1) (a) Ayer, W. A.; Taube, H. Tetrahedron Lett. 1972, 1917. (b) Ayer,
W. A.; Taube, H. Can. J . Chem. 1973, 51, 3842. (c) Ayer, W. A.; Browne,
L. M.; Mercer, J . R.; Taylor, D. R.; Ward, D. E. Can. J . Chem. 1978,
56, 717. (d) Ayer, W. A.; Yoshida, T.; VanSchie, D. M. J . Can. J . Chem.
1978, 56, 2113. (e) Ayer, W. A.; Lee, S. P. Can. J . Chem. 1979, 57,
3332. (f) Ayer, W. A.; Lee, S. P.; Nakashima, T. T. Can. J . Chem. 1979,
57, 3338.
(2) Ayer, W. A.; Browne, L. M. Tetrahedron 1981, 37, 2199.
(3) Shibata, H.; Tokunaga, T.; Karasawa, D.; Hirota, A. Agric. Biol.
Chem. 1989, 53, 3373.
(4) Kawagishi, H.; Shimada, A.; Shirai, R.; Okamoto, K.; Ojima, F.;
Sakamoto, H.; Ishiguro, Y.; Furukawa, S. Tetrahedron Lett. 1994, 35,
1569.
(5) Toyota, M.; Nakaisi, E.; Asakawa, Y. Phytochemistry 1996, 43,
1057.
In tr od u ction of th e F ou r -Ca r bon Sid e Ch a in to
Rin g B. We first thought that alkylation at the C-11
position may occur from the convex face of the ring, so
methylation was first carried out (to 17) and then aldol
condensation with the four-carbon aldehyde 11 was
attempted (Scheme 4). This assumption turned out to
be incorrect. The product 18 was a mixture of two
(6) (a) Ayer, W. A.; Browne, L. M. Tetrahedron 1981, 37, 2199. (b)
Ward, D. E. Can. J . Chem. 1987, 65, 2380. (c) Dahnke, K. R.; Paquette,
L. A. J . Org. Chem. 1994, 59, 885.
(7) Snider, B. B.; Vo, N. H.; O’Neil, S. V.; Foxman, B. M. J . Am.
Chem. Soc. 1996, 118, 7644.
(8) J acobi, P. A.; Murphree, S.; Rupprecht, F.; Zheng, W. J . Org.
Chem. 1996, 61, 2413.
S0022-3263(97)01514-4 CCC: $15.00 © 1998 American Chemical Society
Published on Web 01/01/1998

Total Synthesis of Allocyathin B2
J . Org. Chem., Vol. 63, No. 2, 1998 307
Sch em e 2a
sively from the R face of the ring, and the configuration
at C-10 of 20 is R*. The acetate 21 is the C-10 isomer,
the configuration of which must be S*. These results are
attributed to the fact that the oncoming electron acceptor
reacted from the opposite side of the C-14 methyl group
of compound 17. This is presumably due to the steric
hindrance of the C-14 methyl group of the enolate 17′
(Figure 1) and also to the electronic requirement that the
R-position (axial) is more accessible at C-11. This sug-
gests that in order to synthesize the desired stereochem-
istry, we should first introduce the side chain and then
the methyl group in ketone 8 (vide infra).
P r ep a r a tion of Isoa llocya th in B2 (29). Although
the stereochemistry at the two tertiary methyl groups is
opposite to that desired, we attempted to synthesize
isoallocyathin B2 (33) in order to establish the synthetic
route (Scheme 5). The lactone 22 was first reduced by
LiAlH4. The diol 26 was isolated in only 25% yield along
with the dihydro diol 27 in 14% yield. This step was
studied in detail in the case of allocyathin B2 (vide infra).
The primary alcohol of the diol 26 was protected by a
TBDMS group and the secondary hydroxyl group was
protected with a MOM group to afford 29 in high yield.
Deprotection of both the THP and TBDMS groups was
simply achieved by treatment of 29 with PPTS in MeOH
to afford the diol 30 in quantitative yield. The final steps
were accomplished by the Swern oxidation of 30 to the
aldehyde 31 followed by intramolecular aldol condensa-
tion to give the dienal 32 in moderate yield. Although,
deprotection of the MOM group was realized in only poor
yield,10 the synthesis of isoallocyathin B2 (33), the un-
natural diastereoisomer of natural allocyathin B2 (1), was
thus completed. The protons for the C-10 and C-11
positions of 33 appeared at δ 6.18 and 6.91, which
suffered slightly downfield shifts than those of 1. It is
interesting to note that most other peaks were almost
the same as those of diastereomeric natural allocyathin
B2 (1).
a
Reagents: (a) CH2dCHCH2CH2Br, Mg, CuBr/Me2S, THF; (b)
HOCH2CH2OH, TsOH, C6H6; (c) O3; then Zn, AcOH; (d) CH3CH-
(Br)CH3, Mg, Et2O; (e) J ones oxidation; (f) 5% KOH-MeOH.
Sch em e 3a
a
Reagents: (a) KOH, MeOH, reflux; (b) MeI, acetone, reflux;
(c) dihydropyrane, PPTS, CH2Cl2; (d) LiAlH4, ether; (e) Swern
oxidation; (f) TBDMSCl, NEt3, DMAP, CH2Cl2; (g) TBDPSCl, BuLi,
THF; (h) PDC, DMF; (i) (COCl)2, C6H6.
Acyla tion of th e Keton e 8. The ketone 8 was
alkylated using aldol conditions with the aldehyde 14 to
acetates 34 in 87% yield (Scheme 6). However, the
second alkylation of the acetates 34 was not an easy task,
since elimination was facile. We next attempted acyla-
tion of the ketone 8 with the acid chloride 16.8 Although
a considerable amount of the O-acylated product 36,
which was isolated by HPLC, was obtained, the product
mixture was hydrolyzed without separation to give the
C-acylated product 35 in 37% and the starting ketone 8,
which can be recycled, in 60% yield. The diketone was
methylated using tBuOK/MeI in 91% yield. The product
diastereoisomers,9 whose structures were later revealed
to be isomers at the C-10 position, the four-carbon side
chain being on the R-side at the C-11 position. These
results were revealed by Swern oxidation of the mixture
of TBDMS ether 24 into the diketone 25, which was a
single isomer, stereochemically pure, showing that the
second alkylation occurred exclusively from the R-side of
the molecule at C-11. The mixture of the alcohols 18 was
acetylated (to 19), and two acetoxyl signals were observed
in the NMR spectrum.
was stereochemically homogeneous judging from the 13
C
NMR spectrum. Since reasonable evidence concerning
the stereochemistry could not be obtained by spectral
analysis, compound 37 was deprotected to the alcohol 38
and its spectral data were compared with those of the
isomeric alcohol 25 (vide supra), which had completely
different spectral data.11 Therefore, the stereochemistry
of 38 was established as depicted in the formula.
In tr od u ction of th e C2 Un it a t th e C-5 P osition
(Cycliza tion to th e La cton e). The mixture of acetates
19 was treated with LDA to isolate the hydroxy lactone
20 and acetate 21. Both 20 and 21 were stereochemically
pure single isomers. The lactone 20 was dehydrated
using SOCl2 to afford the R,â-unsaturated lactone 22 and
its isomer 23. The stereochemistries at both the C-10
and 11 positions of 22 were determined from the NOESY
spectrum. NOE’s between the methyl group at C-11 and
that at C-14 and between the protons at C-9, coupled with
H-10, were observed. Thus the two methyl groups are
cis to each other, the aldol condensation occurred exclu-
P r ep a r a tion of th e La cton e 44. The next problem
was the regioselective and stereoselective reduction of the
(10) The poor yield is presumably due to the instability of the
aldehyde group under acidic conditions.
(11) Even after 38 was purified by preparative TLC or HPLC, the
sample showed two spots or two peaks in TLC or HPLC, respectively.
Therefore, compound 38 should exisit in equilibrium with its intramo-
lecular acetal form, although 25 does not.
(9) Heathcock, C. H. Asymmetric Synthesis; Morrison, J . D., Ed.;
Academic Press: San Diego, 1984; Vol. 3, pp 111-206.

308 J . Org. Chem., Vol. 63, No. 2, 1998
Tori et al.
Sch em e 4a
a
Reagents: (a) LDA, MeI, THF, -78 °C; (b) LDA, Et2O, 11, -78 °C; (c) Ac2O, DMAP, Py; (d) LDA, THF; (e) SOCl2, Py, CH2Cl2, 0 °C;
(f) LDA, THF, 14, -78 to -55 °C; (g) Swern oxidation.
Sch em e 5a
F igu r e 1. Transition state model in the reaction of 17.
diketone 37 (Scheme 7). Sodium borohydride reduction
in MeOH gave a mixture of the two diastereoisomers 39
and 40 in 62% yield in a 1:1.4 ratio. However, zinc
borohydride reduction in ether at -78 °C afforded 39 and
40 in 50% yield in the ratio of 15:1.12 When L-Selectride
was used, the ratio of 39 and 40 was 1:12. These ratios
were obtained by transformation into the corresponding
acetates 41 and 42. The stereochemistry was determined
by the following transformation. The acetate 41 was
treated with LHMDS to yield a hydroxy lactone 43 in
80% yield. The NOESY cross peaks were observed
between the methyl group at δ 1.00 (at C-11) and the
protons at C-9 and between the methyl group at δ 0.96
(C-14) and the proton at δ 2.78 (H-6â). Thus the
stereochemistry of the hydroxy lactone 43 was deter-
mined as depicted in the formula. Therefore, this com-
pound was the desired one with all the correct stereo-
chemistries. Compound 43 was dehydrated with SOCl2
and pyridine in CH2Cl2 to afford the R,â-unsaturated
lactone 44 in 50% yield along with the isomeric lactone
45 in 22% yield. The latter could be transformed into
a
Reagents: (a) LiAlH4, THF, reflux; (b) TBDMSCl, NEt3,
DMAP, CH2Cl2; (c) MOMCl, (i-Pr)2NEt, CH2Cl2; (d) PPTS, MeOH;
(e) Swern oxidation; (f) 5% KOH-MeOH; (g) HCl, MeOH.
44 by treatment with potassium carbonate in MeOH
under reflux. The stereochemistry was also confirmed
by the NOESY spectrum for 44. The isomeric acetate
42 was transformed into the lactone 46 by LDA followed
by dehydration to yield the lactone 47. The NOESY
spectrum indicated cross peaks between the proton at δ
4.16 (H-10) and the methyl group at δ 1.21 (C-11). Thus,
zinc borohydride reduction was presumably involved the
chelation of the zinc atom to the diketone moiety and the
hydride attacked from the convex side of this chelate ring
to afford predominantly the S* isomer, realizing regio-
and stereoselective reduction.
Syn th esis of Allocya th in B2 (1). The lactone 44 was
then reduced by LiAlH4 in THF under reflux to afford
the deprotected triol 48, which was isolated by transfor-
mation into the bis-TBDMS ether 49 in 37% overall yield
(Scheme 8). This low yield was also observed in the six-
membered lactone in the case of isoallocyathin B2. When
(12) (a) Gensler, W. J .; J ohnson, F.; Sloan, A. D. B. J . Am. Chem.
Soc. 1960, 82, 6074. (b) Crabbe´, P.; Garcia, G. A.; Rius, C. J . Chem.
Soc., Perkin Trans. 1 1973, 810.

Total Synthesis of Allocyathin B2
J . Org. Chem., Vol. 63, No. 2, 1998 309
Sch em e 6a
Syn th esis of 3-Meth yl-3-(3-bu ten yl)cycloh exa n on e (4).
A solution of the Grignard reagent in THF was prepared from
4-bromo-1-butene (4.80 mL, 47.4 mmol) and Mg (0.93 g, 38.4
mmol) in THF (12 mL). A solution of CuBr‚Me2S (1.55 g, 7.55
mmol) in THF (10 mL) was added into this solution. In 10
min, a solution of 3-methyl-2-cyclohexen-1-one (1.41 g, 12.8
mmol) in THF (3 mL) was added and the mixture was stirred
at -30 °C for 2 h. Saturated NH4Cl solution (10 mL) was
added and the mixture was extracted with ether. The organic
phase was washed with water and brine, dried (MgSO4), and
evaporated to afford the ketone 4 (2.78 g) as an oil: FTIR 1725,
1650 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.94 (3 H, s), 4.94 (1
H, ddt, J ) 10.0, 1.9, 1.0 Hz), 5.01 (1 H, dq, J ) 16.9, 1.9 Hz),
5.80 (1 H, ddt, J ) 16.9, 10.0, 6.5 Hz); 13C NMR (50 MHz,
CDCl3) δ 21.9 (t), 24.7 (q), 27.7 (t), 35.6 (t), 38.4 (s) 40.7 (t),
40.8 (t), 53.5 (t), 114.2 (t), 138.6 (d), 211.8 (s); MS (EI) m/z 166
(M+), 151, 111 (base), 95, 81, 69, 55; EI-HRMS m/z calcd for
C11H18O: 166.1358. Found: 166.1374.
Syn th esis of 3-Meth yl-3-(3-bu ten yl)cycloh exan on e Eth -
ylen e Keta l (5). A solution of the ketone 4 (2.78 g), ethylene
glycol (1.31 g, 21.1 mmol), and TsOH‚H2O (0.27 g) in C6H6 (150
mL) was heated under reflux for 15 h with the aid of a Dean-
Stark water separator. The mixture was washed with satu-
rated NaHCO3 solution, water, and brine. The aqueous layer
was extracted with ether and the ethereal solution was washed
with water and brine. The combined organic layer was dried
(MgSO4) and evaporated to afford a residue, which was
purified by silica gel column chromatography (hexanes-EtOAc
in gradient) to give the ketal 5 (2.66 g, 99%, two steps) as an
oil: FTIR 1650 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.96 (3 H,
s), 3.91 (4 H, m), 4.91 (1 H, ddt, J ) 10.2, 1.6, 1.2 Hz), 5.00 (1
H, dq, J ) 16.8, 1.6 Hz), 5.82 (1 H, ddt, J ) 16.8, 10.2, 6.6
Hz); 13C NMR (50 MHz, CDCl3) δ 19.7 (t), 25.3 (q), 28.1 (t),
34.4 (s), 35.0 (t), 37.1 (t) 42.1 (t), 44.8 (t), 63.9 (t), 64.1 (t), 109.4
(s), 113.7 (t), 139.7 (d); MS (EI) m/z 210 (M+), 195, 167, 155,
153, 139, 126, 113, 99 (base), 86; EI-HRMS m/z calcd for
a
Reagents: (a) LDA, THF, 14, -78 °C; then Ac2O, rt; (b) LDA,
THF, 16, -78 °C; (c) 5% KOH-MeOH; (d) tBuOK, MeI, THF; (e)
TBAF, THF.
DIBALH was used for the reduction, the lactol 52 was
isolated in high yield. The lactol 52 was reduced again
with LiAlH4 in THF under reflux to yield the triol 48 in
poor yield. When it was reduced by NaBH4 in dioxane,
the lactol 52 was obtained in high yield.13 Super hydride
reduction failed to give the diol. Therefore, the best
method so far is to reduce the lactone with LiAlH4 in THF
under reflux for several hours. This is presumably due
to the presence of the double bond at the C-5 and C-6
positions and the fact that the conformation is very rigid.
Since the acetate can be easily removed at the cyclization
step, this may not cause problems with the aldol cycliza-
tion. The alcohol 49 was treated with Ac2O in pyridine
followed by deprotection of the TBDMS group with PPTS
to afford the diol 51 in 52% yield in two steps. Swern
oxidation of the diol 51 afforded the dial 53, and the final
intramolecular aldol cyclization as well as deprotection
of the acetate gave allocyathin B2 (1) in 74% yield. The
spectral data were identical with those of the natural one.
Since the total synthesis of erinacine A (2) was achieved
using dl-allocyathin B2 (1) by Snider et al.,7 this also
constitutes the formal total synthesis of erinacine A (2).
In summary, we have achieved the total synthesis of
allocyathin B2 (1) using aldol reactions in (1) the con-
struction of ring A; (2) the introduction of the two-carbon
unit into the C-5 position, replacing the Wittig processes;
and (3) the preparation of the seven-membered dienal
by intramolecular cyclization. The introduction of an
alkyl group at the C-11 position occurred solely from the
R-side of the molecule (the side opposite the methyl group
at C-14), which means that bond formation selectively
occurred from the axial direction.
C
13H22O2: 210.1620. Found: 210.1633.
Syn th esis of 3-Meth yl-3-(3-h yd r oxy-4-m eth ylp en tyl)-
cycloh exa n on e Eth ylen e Keta l (6). Ozone was bubbled
through a solution of the ketal 5 (1.32 g, 44.5 mmol) in CH2Cl2
(150 mL) at -78 °C for 15 min. Acetic acid (3 mL) and Zn
powder (2.33 g) were added, and the mixture was kept at rt
overnight. The filtrate was washed with water, saturated
NaHCO3 solution, and brine, dried (MgSO4), and evaporated
1
to afford an aldehyde (1.87 g) as an oil: FTIR 1735 cm-1; H
NMR (200 MHz, CDCl3) δ 0.95 (3 H, s), 3.91 (4 H, m), 9.78 (1
H, t, J ) 1.9 Hz); 13C NMR (50 MHz, CDCl3) δ 19.6 (t), 25.8
(q), 33.3 (t), 33.6 (s), 34.1 (t) 37.1 (t), 39.0 (t), 44.6 (t), 63.9 (t),
64.1 (t), 109.2 (s), 203.2 (d); MS (CI) m/z 213 (M + H)+, 195,
184, 169, 155, 141, 113, 99 (base), 86; CI-HRMS m/z calcd for
C
12H21O3 (M + H)+: 213.1491. Found: 213.1507.
A solution of the aldehyde (1.87 g) in dry ether (40 mL) was
added to a solution of the Grignard reagent prepared from
2-bromopropane (10 mL, 0.11 mol) and Mg (2.17 g, 89.3 mmol)
in dry ether (60 mL) during 1 h. The mixture was further
stirred at rt for 1 h. Saturated NH4Cl (100 mL) was added at
0 °C and the mixture was extracted with ether. The organic
phase was washed with water and brine, dried (MgSO4), and
evaporated to afford the alcohol 6 (1.36 g, 83%, two steps) as
an oil: FTIR 3470 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.92 (6
H, d, J ) 7.3 Hz), 0.95 (3 H, s), 3.30 (1 H, m), 3.91 (4 H, m);
13C NMR (50 MHz, CDCl3) δ 17.1 (q), 18.9 (q), 19.6 (t), 25.8
(q), 28.0 (t) 33.1 (d), 34.3 (s), 34.9 (t), 37.6 (t), 38.0 (t), 44.5 (t),
63.9 (t), 64.0 (t), 77.3 (d), 109.8 (s); MS (EI) m/z 256 (M+), 241,
213, 195, 155 (base), 111, 99, 86; EI-HRMS m/z calcd for
C
15H28O3: 256.2038. Found: 256.2045.
Syn th esis of 3-Meth yl-3-(4-m eth yl-3-oxop en tyl)cyclo-
h exa n on e (7). A solution of the alcohol 6 (3.75 g, 14.6 mmol)
in acetone (30 mL) was treated with the J ones reagent (12.0
mL) at 0 °C. The mixture was stirred for 25 min and
2-propanol (15.0 mL) was added. Water was added and
acetone was evaporated. The mixture was extracted with
ether and the organic solution was washed with brine to afford
Exp er im en ta l Section
Gen er a l. Silica gel 60 (70-230 mesh, Merck) was used for
column chromatography, and silica gel 60F254 plates (0.25, 0.5,
1.0 mm, Merck) were used for TLC.
1
the diketone 7 (3.33 g) as an oil: FTIR 1725 cm-1; H NMR
(13) Ohmori, K.; Nishiyama, S.; Yamamura, S. Tetrahedron Lett.
1995, 36, 6519.
(200 MHz, CDCl3) δ 0.91 (3 H, s), 1.10 (3 H, d, J ) 6.9 Hz),

310 J . Org. Chem., Vol. 63, No. 2, 1998
Tori et al.
Sch em e 7a
a
Reagents: (a) NaBH4, MeOH, 0 °C; (b) Zn(BH4)2, Et2O, -78 °C; (c) Ac2O, DMAP, Py; (d) LHMDS, THF, -78 °C; (e) LDA, THF, -78
°C; (f) SOCl2, Py, CH2Cl2, 0 °C; (g) K2CO3, MeOH, reflux (52%, 44:45 ) 3:1).
Sch em e 8a
evaporated to afford a residue, which was purified by silica
gel column chromatography (hexanes-EtOAc in gradient) to
give the enone 8 (1.24 g, 73%, 2 steps) as an oil: FTIR 1690,
1630 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.94 (3 H, d, J ) 6.9
Hz), 0.98 (3 H, s), 1.00 (3 H. d, J ) 6.9 Hz), 3.42 (1 H, septet,
J ) 6.9 Hz); 13C NMR (50 MHz, CDCl3) δ 21.0 (q × 2), 21.4 (t),
24.2 (q), 27.2 (d), 28.5 (t) 38.6 (t), 40.2 (t), 41.8 (t), 48.6 (s),
138.6 (s), 159.1 (s), 201.3 (s); MS (EI) m/z 192 (M+), 177 (base),
159, 149, 135, 121, 107, 93, 79, 67; EI-HRMS m/z calcd for
C
13H20O: 192.1515. Found: 192.1496.
Syn th esis of 35. A solution of the ketone 8 (543.0 mg, 2.83
mmol) in dry THF (5 mL) was treated with a solution of LDA
i
prepared from BuLi (1.68 M, 2.20 mL, 3.70 mmol) and Pr2-
NH (0.56 mL, 4.27 mmol) at -78 °C for 1 h. The acid chloride
16 (prepared from 1.17 g of the corresponding carboxylic acid
15 by treatment with oxalyl chloride) was added to this
solution and the mixture was stirred for 30 min. Saturated
NH4Cl solution and ether were added, and the organic layer
was washed with brine, dried (MgSO4), and evaporated to
afford a residue. The residue was treated with 5% KOH in
MeOH (10 mL) at 0 °C for 30 min. Water was added and the
mixture was extracted with ether. The organic layer was
washed with brine, dried (MgSO4), and evaporated to afford a
residue, which was purified by silica gel column chromatog-
raphy (hexanes-EtOAc in gradient) to give the diketone 35
(486.3 mg, 33%) and the ketone 8 (325 mg, 60%) each as an
oil.
35: FTIR 1630, 1590, 1560 cm-1; 1H NMR (200 MHz, CDCl3)
δ 0.95 (3 H, s), 1.04 (3 H, d, J ) 6.8 Hz), 1.04 (3 H, d, J ) 6.8
Hz), 1.05 (9 H, s), 3.72 (2 H, t, J ) 6.0 Hz), 3.83 (1 H, septet,
J ) 6.8 Hz), 7.39 (6 H, m), 7.65 (4 H, m), 16.17 (1 H, s); 13C
NMR (50 MHz, CDCl3) δ 19.2 (s), 21.1 (q), 21.3 (q), 21.9 (q),
22.5 (t) 26.9 (q × 3), 27.3 (t), 27.9 (d), 29.7 (t), 34.3 (t), 36.1 (t),
38.3 (t), 46.0 (s), 63.2 (t), 106.4 (s), 127.6 (d × 4), 127.8 (s),
129.6 (d × 2), 133.9 (s × 2), 135.6 (d × 4), 159.3 (s), 171.5 (s),
203.0 (s); MS (CI) m/z 517 (M + H)+, 501, 459 (base), 439, 381,
361, 261; CI-HRMS m/z calcd for C33H45O3Si (M + H)+:
517.3138. Found: 517.3147.
a
Reagents: (a) LiAlH4, THF, reflux; (b) TBDMSCl, NEt3,
CH2Cl2 (37% from 44); (c) Ac2O, DMAP, Py; (d) PPTS, MeOH (52%
from 49); (e) Swern oxidation; (f) 5% KOH-MeOH (74% from 51).
2.62 (1 H, septet, J ) 6.9 Hz); 13C NMR (50 MHz, CDCl3) δ
18.2 (q × 2), 21.9 (t), 24.2 (q), 34.3 (t), 35.0 (t) 35.8 (t), 37.9 (s),
40.7 (t), 40.8 (d), 53.1 (t), 211.4 (s), 214.1 (s); MS (EI) m/z 210
(M+), 192, 167, 149, 121, 111 (base), 95, 81, 71; EI-HRMS m/z
calcd for C13H22O2: 210.1619. Found: 210.1615.
Syn th esis of 9-Isop r op yl-6-m eth ylbicyclo[4.3.0]n on -
1(9)-en -2-on e (8). The diketone 7 (2.00 g) was treated with
5% KOH in MeOH (5 mL) under reflux for 12 h. The solvent
was evaporated and the mixture was extracted with ether. The
organic layer was washed with brine, dried (MgSO4), and
Syn th esis of 37. A solution of the diketone 35 (486.3 mg,
0.94 mmol) in dry THF (5 mL) was added to a solution of KOt-
Bu (118.0 mg, 1.05 mmol) in dry THF (5 mL) at 0 °C. Then
the mixture was stirred at rt for 1 h before addition of MeI

Total Synthesis of Allocyathin B2
J . Org. Chem., Vol. 63, No. 2, 1998 311
(0.12 mL, 1.93 mmol). The mixture was stirred at rt for 1.5 h
and then water was added. The mixture was extracted with
ether and the organic layer was washed with brine, dried
(MgSO4), and evaporated to afford a residue. The residue was
purified by silica gel column chromatography (hexanes-EtOAc
in gradient) to give the diketone 37 (454.5 mg, 91%) as an oil:
6.8 Hz), 3.65 (2 H, br t, J ) 5.6), 5.51 (1 H, br d, J ) 8.8 Hz),
7.38 (6 H, m), 7.63 (4 H, m); 13C NMR (50 MHz, CDCl3) δ 19.2
(s), 20.8 (q), 21.0 (q), 21.2 (q), 23.1 (q), 24.4 (q) 26.8 (q × 3),
27.1 (d), 27.6 (t × 2), 29.1 (t), 29.9 (t), 34.5 (t), 40.0 (t), 49.0
(s), 52.1 (s), 63.7 (t), 78.0 (d), 127.6 (d × 4), 129.5 (d × 2), 134.1
(s × 2), 135.5 (d × 4), 137.0 (s), 160.9 (s), 170.8 (s), 203.8 (s);
MS (CI) m/z 575 (M + H)+, 559, 543, 517, 497, 457, 437 (base),
419, 319, 259, 199, 177; CI-HRMS m/z calcd for C36H51O4Si
(M + H)+: 575.3557. Found: 575.3567.
FTIR 1715, 1665, 1610 cm-1 1H NMR (200 MHz, CDCl3) δ
;
0.96 (3 H, d, J ) 6.8 Hz), 1.03 (3 H, d, J ) 6.8 Hz), 1.03 (9 H,
s), 1.12 (3 H, s), 1.28 (3 H, s), 1.49 (1 H, dt, J ) 13.8, 3.6 Hz),
3.38 (1 H, septet, J ) 6.8 Hz), 3.68 (2 H, t, J ) 6.0), 7.39 (6 H,
m), 7.65 (4 H, m); 13C NMR (50 MHz, CDCl3) δ 19.2 (s), 20.8
(q × 2), 21.2 (q), 24.8 (q), 26.9 (q × 3) 27.3 (d), 27.3 (t), 29.1
(t), 31.0 (t), 34.6 (t), 36.2 (t), 40.1 (t), 48.9 (s), 62.7 (s), 63.2 (t),
127.6 (d × 4), 129.5 (d × 2), 133.9 (s × 2), 135.5 (d × 4), 136.3
(s), 162.9 (s), 202.1 (s), 210.6 (s); MS (CI) m/z 531 (M + H)+,
515, 473, 453, 395, 375, 325, 275 (base), 199, 151; CI-HRMS
m/z calcd for C34H47O3Si (M + H)+: 531.3294. Found: 531.3293.
Syn th esis of 38. The diketone 37 (28.1 mg, 0.053 mmol)
was treated with TBAF (1.0 M, 0.10 mL) at rt for 2.5 h. Water
was added and the mixture was extracted with ether. The
organic layer was washed with brine, dried (MgSO4), and
evaporated to afford a residue. The residue was chromato-
graphed over silica gel (hexanes-EtOAc in gradient) to give
the alcohol 38 (10.2 mg, 66%) as an oil: FTIR 3400, 1715, 1670
42: FTIR 1740, 1675, 1610 cm-1; 1H NMR (200 MHz, CDCl3)
δ 0.93 (3 H, d, J ) 6.9 Hz), 0.99 (3 H, d, J ) 6.9 Hz), 1.028 (3
H, s), 1.033 (3 H, s), 1.04 (9 H, s), 1.94 (3 H, s), 3.40 (1 H,
septet, J ) 6.9 Hz), 3.70 (2 H, m), 5.46 (1 H, br dd, J ) 10.4,
2.4 Hz), 7.38 (6 H, m), 7.64 (4 H, m); 13C NMR (50 MHz, CDCl3)
δ 19.2 (s), 20.8 (q), 21.1 (q), 21.3 (q), 21.9 (q), 24.0 (q) 25.6 (t),
26.9 (q × 3), 26.9 (d), 28.2 (t), 29.1 (t), 29.4 (t), 35.0 (t), 39.7
(t), 48.8 (s), 51.8 (s), 63.5 (t), 76.2 (d), 127.6 (d × 4), 129.5 (d ×
2), 134.0 (s × 2), 135.5 (d × 4), 136.9 (s), 160.6 (s), 170.1 (s),
203.0 (s); MS (CI) m/z 575 (M + H)+, 559, 515, 497, 457, 437
(base), 259, 61; CI-HRMS m/z calcd for C36H51O4Si (M + H)+:
575.3556. Found: 575.3532.
Red u ction of 37 by L-Selectr id e. A solution of 37 (72.2
mg, 0.14 mmol) in THF (2.5 mL) was treated with L-Selectride
in THF (6.0 mL) at -78 °C for 4.5 h. Water and ether were
added, and the organic layer was washed with brine, dried
(MgSO4), and evaporated to afford a residue. The residue was
purified by silica gel column chromatography (hexanes-EtOAc
in gradient) to give a mixture of alcohols 39 and 40 (51.6 mg,
0.097 mmol, 71%). The mixture of alcohols (49.5 mg, 0.093
mmol) in pyridine (0.7 mL) was treated with Ac2O (0.5 mL)
and DMAP (23.8 mg, 0.19 mmol) at rt for 18.5 h. MeOH (3
mL) was added at 0 °C and the solvent was evaporated. The
mixture was extracted with ether and the organic layer was
washed with brine, dried (MgSO4), and evaporated to afford a
residue. The residue was separated by silica gel column
chromatography (hexanes-EtOAc in gradient) to give the
acetates 41 and 42 (48.2 mg, 90%) in a ratio of 1:12.
1
cm-1; H NMR (200 MHz, CDCl3) δ 0.96 (3 H, d, J ) 6.9 Hz),
1.02 (3 H, d, J ) 6.9 Hz), 1.13 (3 H, s), 1.30 (3 H, s), 3.14 (1 H,
septet, J ) 6.9 Hz), 3.67 (2 H, t, J ) 5.6 Hz; MS (CI) m/z 291
(M - H)+, 275 (M - H2O + H)+ (base), 259, 205, 151, 124, 87;
CI-HRMS m/z calcd for
Found: 291.1958.
C
18H27O3 (M - H)+: 291.1960.
Red u ction of 37 by Na BH4. A solution of 37 (454.5 mg,
0.86 mmol) in MeOH (5 mL) was added to a suspension of
NaBH4 (40.0 mg, 1.06 mmol) in MeOH (5 mL) at 0 °C. More
NaBH4 (10 mg) was added in 1.5 h, 9 mg in 2.5 h, and 12 mg
in 4 h, respectively. Water and ether were added, and the
organic layer was washed with brine, dried (MgSO4), and
evaporated to afford a residue. The residue was purified by
silica gel column chromatography (hexanes-EtOAc in gradi-
ent) to give a mixture of alcohols 39 and 40 (282.7 mg, 1:1.4,
62%).
Red u ction of 37 by Zn (BH4)2. A solution of diketone 37
(76.9 mg, 0.15 mmol) in dry ether (2 mL) was treated with
Zn(BH4)2 in ether (60 mL) at -78 °C for 11 h. Water and
AcOH were added, and the organic layer was washed with
brine, dried (MgSO4), and evaporated to afford a residue. The
residue was purified by silica gel column chromatography
(hexanes-EtOAc in gradient) to give a mixture of alcohols 39
and 40 (38.9 mg, 15:1, 50%) as an oil.
Data corresponding to the S*-alcohol 39: FTIR 3480, 1660,
1610 cm-1; 1H NMR (200 MHz, CDCl3) δ 0.98 (3 H, d, J ) 7.0
Hz), 1.02 (3 H, s), 1.04 (3 H, d, J ) 7.0 Hz), 1.07 (9 H, s), 1.04
(3 H, s), 3.28 (1 H, septet, J ) 7.0 Hz), 3.72 (1 H, td, J ) 11.5,
5.9), 3.78 (1 H, td, J ) 11.5, 5.9 Hz), 3.83 (1 H, br d, J ) 10.4
Hz), 7.38 (6 H, m), 7.70 (4 H, m); 13C NMR (50 MHz, CDCl3)
δ 17.8 (q), 19.2 (s), 20.8 (q), 21.3 (q), 24.4 (q), 26.8 (q × 3) 27.0
(t), 27.2 (d), 29.3 (t), 29.5 (t), 31.0 (t), 34.9 (t), 40.0 (t), 49.4 (s),
51.2 (s), 63.9 (t), 75.4 (d), 127.5 (d × 4), 129.5 (d × 2), 134.0 (s
× 2), 135.5 (d × 4), 137.5 (s), 160.0 (s), 210.0 (s); MS (CI) m/z
533 (M + H)+, 515, 475, 455, 397, 377, 327, 269, 249, 207
(base), 191, 71; CI-HRMS m/z calcd for C34H49O3Si (M + H)+:
533.3451. Found: 533.3445.
Syn th esis of 43. A solution of the acetate 41 (39.3 mg,
0.069 mmol) in dry THF (0.4 mL) was treated with LHMDS
(1.0M, 0.08 mL) at -78 °C for 1 h. More LHMDS (1.0 M, 0.15
mL) was added and the mixture was further stirred for 1.5 h.
Ether and saturated NH4Cl solution were added and the
organic layer was washed with brine, dried (MgSO4), and
evaporated to afford a residue. The residue was purified by
silica gel column chromatography (hexanes-EtOAc in gradi-
ent) to give the hydroxy lactone 43 (31.2 mg, 80%) as an oil:
1
FTIR 3500, 1750 cm-1; H NMR (200 MHz, CDCl3) δ 0.93 (3
H, d, J ) 6.8 Hz), 0.96 (3 H, s), 1.00 (3 H, d, J ) 6.8 Hz), 1.00
(3 H, s), 1.05 (9 H, s), 2.18 (1 H, ddd, J ) 16.0, 8.7, 0.4 Hz),
2.33 (1 H, ddd, J ) 16.0, 10.9, 6.1 Hz), 2.66 (1 H, d, J ) 15.1
Hz), 2.78 (1 H, dd, J ) 15.1, 2.4 Hz), 3.48 (1 H, septet, J ) 6.8
Hz), 3.67 (1 H, ddd, J ) 10.2, 6.7, 5.6 Hz), 3.73 (1 H, ddd, J )
10.0, 5.8, 5.8 Hz), 3.92 (1 H, dd, J ) 6.5, 6.1 Hz), 7.38 (6 H,
m), 7.64 (4 H, m); 13C NMR (50 MHz, CDCl3) δ 16.6 (q), 19.2
(s), 21.3 (q), 22.1 (q), 23.6 (q) 26.4 (t), 26.9 (q × 3), 27.3 (d),
28.0 (t), 29.5 (t), 33.4 (t × 2), 40.8 (t), 42.0 (s), 42.9 (t), 47.2 (s),
63.4 (t), 75.6 (s), 86.4 (d), 127.7 (d × 4), 129.6 (d × 2), 133.9 (s
× 2), 135.6 (d × 4), 140.1 (s), 148.1 (s), 172.1 (s); MS (CI) m/z
575 (M + H)+, 533, 497, 472, 439, 373, 327, 269, 249, 221, 207,
193, 179, 71 (base); CI-HRMS m/z calcd for C36H51O4Si (M +
H)+: 575.3556. Found: 575.3572.
A solution of the alcohols (187.2 mg, 0.35 mmol) in pyridine
(7 mL) was treated with Ac2O (5 mL) and DMAP (42 mg) at rt
for 10 h. Methanol (10 mL) and water were added, and the
solvent was removed. The mixture was extracted with ether
and the organic layer was washed with water, 1 M HCl
solution, saturated NaHCO3 solution, and brine, dried (Mg-
SO4), and evaporated to afford a residue. The residue was
purified by silica gel column chromatography (hexanes-EtOAc
in gradient) to give the acetates 41 (186.4 mg, 92%) and 42
(12.0 mg, 6%), each as an oil.
Syn th esis of 44. A solution of SOCl2 (0.12 mL) in CH2Cl2
(2 mL) was added to a solution of the hydroxy lactone 43 (73.3
mg, 0.13 mmol) in pyridine (0.54 mL) and CH2Cl2 (4 mL) at 0
°C. The mixture was stirred for 15 min. Water was added
and the mixture was extracted with CH2Cl2. The organic layer
was washed with brine, dried (MgSO4), and evaporated to
afford a residue. The residue was purified by silica gel column
chromatography (hexanes-EtOAc in gradient) to give a mix-
ture of the lactones 44 and 45 (59 mg). HPLC separation
(Nucleosil 50-5, 4.6 × 250, hexane-EtOAc 96.5:3.5, 3.0 mL/
min) afforded 44 (31.9 mg, 50%) and 45 (15.9 mg, 22%), each
as an oil.
41: FTIR 1740, 1670, 1610 cm-1; 1H NMR (200 MHz, CDCl3)
δ 0.95 (3 H, d, J ) 6.8 Hz), 1.01 (3 H, d, J ) 6.8 Hz), 1.01 (3
H, s), 1.03 (9 H, s), 1.06 (3 H, s), 2.04 (3 H, s), 2.41 (1 H, dd,
J ) 7.6, 2.0 Hz), 2.44 (1 H, t, J ) 9.0), 3.37 (1 H, septet, J )
44: FTIR 1715, 1630, 1610 cm-1; 1H NMR (600 MHz, CDCl3)
δ 0.96 (3 H, s), 0.97 (3 H, s), 0.97 (3 H, d, J ) 6.9 Hz), 1.03 (3

312 J . Org. Chem., Vol. 63, No. 2, 1998
Tori et al.
H, d, J ) 6.9 Hz), 1.05 (9 H, s), 1.75 (1 H, m), 1.80 (1 H, ddd,
J ) 12.4, 7.7, 2.6 Hz), 2.00 (1 H, m), 2.43 (1 H, ddd, J ) 16.7,
9.6, 2.5 Hz), 2.47 (1 H, ddd, J ) 17.3, 9.6, 7.7 Hz), 2.91 (1 H,
septet, J ) 6.9 Hz), 3.69 (1 H, ddd, J ) 10.4, 6.6, 5.2 Hz), 3.77
(1 H, ddd, J ) 10.4, 6.3, 4.9 Hz), 4.03 (1 H, dd, J ) 10.4, 1.9
Hz), 5.72 (1 H, s), 7.38 (6 H, m), 7.65 (4 H, m); 13C NMR (150
MHz, CDCl3) δ 16.8 (q), 19.2 (s), 21.4 (q), 21.6 (q), 23.4 (q),
25.1 (t) 26.9 (q × 3), 26.9 (d), 28.8 (t), 29.2 (t), 32.7 (t), 36.0 (t),
39.0 (t), 39.4 (s), 48.6 (s), 63.3 (t), 85.4 (d), 114.2 (d), 127.6 (d
× 4), 129.6 (d × 2), 133.9 (s × 2), 134.6 (s), 135.6 (d × 4), 151.2
(s), 160.7 (s), 166.1 (s); MS (CI) m/z 557 (M + H)+, 499 (base),
479, 421, 242, 199; CI-HRMS m/z calcd for C36H49O3Si (M +
H)+: 557.3451. Found: 557.3456.
Red u ction of 44. A solution of 44 (31.9 mg, 0.057 mmol)
in dry THF (5 mL) was heated under reflux with LiAlH4 (60.0
mg, 1.58 mmol) for 1 h. Wet ether and water were added, and
the organic layer was washed with brine, dried (MgSO4), and
evaporated to afford the triol 48 (25.0 mg) as an oil: FTIR
1
3310, 1650, 1620 cm-1; H NMR (200 MHz, CDCl3) δ 0.94 (3
H, s), 0.95 (3 H, d, J ) 6.4 Hz), 0.99 (3 H, d, J ) 6.4 Hz), 1.05
(3 H, s), 2.84 (1 H, septet, J ) 6.4 Hz), 3.71 (2 H, t, J ) 5.6),
3.97 (1 H, br d, J ) 10.0 Hz), 4.18 (1 H, dd, J ) 13.2, 6.8 Hz),
4.28 (1 H, dd, J ) 13.2, 6.8 Hz), 5.26 (1 H, t, J ) 6.8 Hz); 13C
NMR (50 MHz, CDCl3) δ 21.4 (q), 21.7 (q), 22.8 (q), 24.1 (q),
26.5 (d), 28.1 (t), 29.5 (t), 29.7 (t), 30.5 (t), 36.3 (t), 38.8 (t),
46.8 (s), 48.1 (s), 59.8 (t), 62.7 (t), 77.4 (d), 125.5 (d), 141.5 (s),
141.6 (s), 143.0 (s); MS (CI) m/z 323 (M + H)+, 322, 304, 287
(base), 269, 234, 217, 201, 71; CI-HRMS m/z calcd for C20H35O3
(M + H)+: 323.2586. Found: 323.2581.
1
45: FTIR 1735 cm-1; H NMR (200 MHz, CDCl3) δ 1.00 (3
H, s), 1.01 (3 H, d, J ) 6.2 Hz), 1.03 (3 H, s), 1.05 (9 H, s) 1.14
(3 H, d, J ) 6.2 Hz), 3.40 (1 H, d, J ) 21.7 Hz), 3.67 (1 H, d,
J ) 21.7), 3.67 (1 H, dt, J ) 10.1, 5.6 Hz), 3.78 (1 H, dt, J )
10.1, 5.2 Hz), 4.07 (1 H, br d, J ) 10.5 Hz), 5.77 (1 H, br t, J
) 0.7 Hz), 7.38 (6 H, m), 7.65 (4 H, m); MS (CI) m/z 557 (M +
H)+, 499 (base), 479, 421, 199; CI-HRMS m/z calcd for
Syn th esis of 49. A solution of the triol 48 (12.0 mg, 0.037
mmol) in CH2Cl2 (3 mL) was treated with NEt3 (0.10 mL, 0.72
mmol), DMAP (31.9 mg, 0.26 mmol), and TBDMSCl (43.6 mg,
0.29 mmol) at rt for 1.3 h. Water was added and the mixture
was extracted with CH2Cl2. The organic layer was washed
with 1 M HCl solution, saturated NaHCO3 solution, and brine,
dried (MgSO4), and evaporated to afford a residue. The residue
was purified by silica gel column chromatography (hexanes-
EtOAc in gradient) to give the monoalcohol 49 (23.1 mg) as
C
36H49O3Si (M + H)+: 557.3451. Found: 557.3479.
Isom er iza tion of 45 to 44. A mixture of 45 (15.9 mg, 0.028
mmol), K2CO3 (130 mg), and MeOH (10 mL) was heated under
reflux for 21 h. MeOH was removed and the mixture was
extracted with ether. The organic layer was washed with
brine, dried (MgSO4), and evaporated to afford a residue. The
residue was purified by silica gel column chromatography
(hexanes-EtOAc in gradient) to give a mixture of 44 and 45
(8.3 mg, 52%) in the ratio of 2:1.
an oil: FTIR 3400 cm-1 1H NMR (200 MHz, CDCl3) δ 0.07
;
(12 H, s), 0.90 (18 H, s), 0.92 (3 H, s), 0.95 (3 H, d, J ) 6.8 Hz),
0.97 (3 H, d, J ) 6.8 Hz), 1.04 (3 H, s), 2.28 (2 H, br dd, J )
8.9, 5.9 Hz), 2.89 (1 H, septet, J ) 6.8 Hz), 3.64-3.81 (3 H,
m), 4.21 (1 H, dd, J ) 13.9, 5.1 Hz), 4.39 (1 H, dd, J ) 13.9,
6.4 Hz), 5.15 (1 H, dd, J ) 6.4, 5.1 Hz); MS (CI) m/z 551 (M +
H)+, 533, 493, 418, 401, 361, 269, 203 (base), 145, 71; CI-HRMS
Syn th esis of 46. A solution of the acetate 42 (33.8 mg,
0.059 mmol) in dry THF (1 mL) was treated with LDA
i
prepared from BuLi (1.63 M, 0.19 mL, 0.30 mmol) and Pr2-
NH (0.05 mL, 0.38 mmol) in dry THF (1 mL) at -78 °C for 40
min. Ether and 1 M HCl solution were added, and the organic
layer was washed with brine, dried (MgSO4), and evaporated
to afford a residue. The residue was purified by silica gel
column chromatography (hexanes-EtOAc in gradient) to give
the hydroxy lactone 46 (20.7 mg, 61%) as an oil: FTIR 3480,
m/z calcd for C
32H63O3Si2 (M + H)+: 551.4316. Found:
551.4337.
Syn th esis of 51. A solution of 49 (23.1 mg) in pyridine
(3.5 mL) was treated with Ac2O (2.5 mL) and DMAP (27.8 mg)
at rt for 3.5 h. MeOH (10 mL) was added at 0 °C and the
solvent was evaporated. The mixture was extracted with ether
and the organic layer was washed with brine, dried (MgSO4),
and evaporated to afford the acetate 50. A solution of 50 in
MeOH (2 mL) was treated with PPTS (98.1 mg) at rt for 4 h.
Water was added and the solvent was evaporated. The
mixture was extracted with ether and the organic layer was
washed with brine, dried (MgSO4), and evaporated to afford a
residue. The residue was purified by silica gel column chro-
matography (hexanes-EtOAc in gradient) to give the diol 51
(7.1 mg, 52%, three steps) as an oil: FTIR 3350, 1730, 1660
cm-1; 1H NMR (200 MHz, CDCl3) δ 0.92 (3 H, s), 0.94 (3 H, d,
J ) 6.8 Hz), 0.97 (3 H, s), 0.99 (3 H, d, J ) 6.8 Hz), 2.09 (3 H,
s), 2.81 (1 H, sept, J ) 6.4 Hz), 3.63 (1 H, dd, J ) 7.4, 5 Hz),
3.75 (2 H, t, J ) 5 Hz), 4.25 (1 H, dd, J ) 13.2, 6.2 Hz), 4.38
(1 H, dd, J ) 13.2, 8.8 Hz), 5.28 (1 H, dd, J ) 8.8, 6.2 Hz); MS
(CI) m/z 363 (M - 1)+, 319, 303, 287 (base), 269, 243, 233, 215;
1
1720, 1640 cm-1; H NMR (200 MHz, CDCl3) δ 0.88 (3 H, s),
0.94 (3 H, d, J ) 6.8 Hz), 1.02 (3 H, d, J ) 6.8 Hz), 1.04 (3 H,
s), 1.05 (9 H, s), 2.78 (1 H, dd, J ) 18.9, 0.8 Hz), 2.92 (1 H, dd,
J ) 18.9, 1.6 Hz), 3.49 (1 H, septet J ) 6.8 Hz), 3.68 (1 H,
ddd, J ) 10.6, 5.3, 5.3 Hz), 3.78 (1 H, ddd, J ) 10.6, 6.0, 4.8
Hz), 4.52 (1 H, br dd, J ) 9.8, 2.0 Hz), 7.38 (6 H, m), 7.65 (4
H, m); 13C NMR (100 MHz, C6D6) δ 17.8 (q), 19.5 (s), 21.4 (q),
22.3 (q), 24.8 (t) 25.3 (q), 25.9 (t), 27.1 (d), 27.2 (q × 3), 28.4
(t), 29.9 (t), 34.1 (t), 41.6 (s), 42.5 (t), 42.6 (t), 42.7 (s), 63.8 (t),
76.8 (s), 81.3 (d), 128.1 (d × 4), 130.0 (d × 2), 134.4 (s × 2),
136.0 (d × 4), 140.5 (s), 145.5 (s), 169.2 (s); MS (CI) m/z 575
(M + H)+, 573 (M - H)+, 517, 497, 479 (base), 419, 401, 199;
CI-HRMS m/z calcd for C36H49O4Si (M - H)+: 573.3400.
Found: 573.3390.
Syn th esis of 47. A solution of SOCl2 (0.06 mL) in CH2Cl2
(1 mL) was added to a solution of the hydroxy lactone 46 (17.2
mg, 0.030 mmol) in pyridine (0.13 mL) and CH2Cl2 (1 mL) at
0 °C. The mixture was stirred for 15 min. Water was added
and the mixture was extracted with CH2Cl2. The organic layer
was washed with brine, dried (MgSO4), and evaporated to
afford a residue. The residue was purified by silica gel column
chromatography (hexanes-EtOAc in gradient) to give the
CI-HRMS m/z calcd for
Found: 363.2509.
C
22H35O4 (M - H)+: 363.2535.
Syn th esis of Allocya th in B2 (1). A solution of the diol
51 (3.1 mg, 0.085 mmol) in dry CH2Cl2 (0.34 mL) was treated
with oxalyl chloride (0.04 mL, 0.46 mmol) and DMSO (0.06
mL, 0.85 mmol) in CH2Cl2 (1 mL) at -50 °C. In 15 min, NEt3
(0.24 mL, 1.72 mmol) was added and the mixture was stirred
for 5 min. Water and more CH2Cl2 were added, and the
organic layer was washed with brine, dried (MgSO4), and
evaporated to afford the dialdehyde 53. A solution of the
dialdehyde 53 was treated with 5% KOH in MeOH (2 mL) at
rt for 1 h. Water was added and the solvent was removed.
The mixture was extracted with EtOAc and the organic layer
was washed with brine, dried (MgSO4), and evaporated to
afford a residue. The residue was purified by silica gel column
chromatography (hexanes-EtOAc in gradient) to give allo-
cyathin B2 (1) (1.9 mg, 74% for 2 steps) as an oil: FTIR 3450,
lactone 47 (11.5 mg, 69%) as an oil: FTIR 1715, 1610 cm-1
;
1H NMR (600 MHz, CDCl3) δ 0.97 (3 H, d, J ) 6.9 Hz), 0.98 (3
H, s), 1.04 (9 H, s), 1.04 (3 H, d, J ) 6.9 Hz), 1.21 (3 H, s), 1.27
(1 H, dt, J ) 13.5, 3.3 Hz), 2.41 (1 H, ddd, J ) 14.9, 9.8, 2.2
Hz), 2.46 (1 H, ddd, J ) 17.0, 9.8, 7.7 Hz), 2.92 (1 H, septet, J
) 6.9 Hz), 3.68 (1 H, ddd, J ) 10.2, 6.5, 5.1 Hz), 3.75 (1 H,
ddd, J ) 10.2, 6.6, 5.2 Hz), 4.16 (1 H, dd, J ) 11.0, 3.3 Hz),
5.72 (1 H, s), 7.38 (6 H, m), 7.64 (4 H, m); 13C NMR (150 MHz,
CDCl3) δ 19.2 (s), 21.4 (q), 21.5 (q), 23.8 (q), 24.7 (q), 26.2 (t)
26.9 (q × 3), 27.1 (d), 28.7 (t), 29.2 (t), 30.0 (t), 35.8 (t), 39.1
(t), 39.7 (s), 48.5 (s), 63.1 (t), 85.3 (d), 114.0 (d), 127.6 (d × 4),
129.6 (d × 2), 133.8 (s), 133.9 (s), 134.7 (s), 135.5 (d × 4), 151.9
(s), 157.3 (s), 164.7 (s); MS (CI) m/z 557 (M + H)+, 521, 499,
479 (base), 199; CI-HRMS m/z calcd for C36H49O3Si (M + H)+:
557.3451. Found: 557.3425.
1
1670, 1630, 1570 cm-1; H NMR (600 MHz, CDCl3) δ 0.96 (3
H, s), 0.97 (3 H, d, J ) 6.9 Hz), 1.00 (3 H, s), 1.05 (3 H, d, J )
6.9 Hz), 1.34 (1 H, dt, J ) 14.0, 3.6 Hz), 1.61 (1 H, d, J ) 9.9
Hz, -OH), 1.65-1.69 (3 H, m), 1.74 (1 H, ddd, J ) 12.9, 7.7,
4.9 Hz), 2.41 (1 H, d, J ) 13.7 Hz), 2.42 (1 H, dd, J ) 9.3, 2.7

Total Synthesis of Allocyathin B2
J . Org. Chem., Vol. 63, No. 2, 1998 313
Hz), 2.53 (1 H, dd, J ) 19.5, 5.8 Hz), 2.55 (1 H, br d, J ) 18.4
Hz), 2.83 (1 H, septet, J ) 6.9 Hz), 3.17 (1 H, dd, J ) 18.4, 5.8
Hz), 3.72 (1 H, br dd, J ) 9.9, 5.8), 5.94 (1 H, d, J ) 8.2 Hz),
6.82 (1 H, dd, J ) 8.2, 2.5 Hz), 9.45 (1 H, s); MS (EI) m/z 300
(M+) (base), 285, 267, 239, 211, 197, 183, 155, 128, 105, 91;
EI-HRMS m/z calcd for C20H28O2: 300.2089. Found: 300.2100.
due. We also express our thanks to Prof. W. A. Ayer,
University of Alberta, Canada, for reading the manu-
script.
1
Su p p or tin g In for m a tion Ava ila ble: Copies of H NMR
spectra and experimental details for compounds 10-34 (51
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
Ack n ow led gm en t. We thank Dr. Hirokazu Kawag-
ishi, Shizuoka University, for sending us the NMR
spectra of allocyathin B2. The 600 MHz NMR and MS
spectra were taken by Dr. M. Tanaka and Miss Y.
Okamoto (This University), to whom many thanks are
J O971514S