- Email: [email protected]
Stereoselective total synthesis of (+)-lycoricidine
Stereoselective
Noritaka
Department
Total Synthesis
Chida,
Masami
of Applied Chemisuy,
Ohtsuka,
of (+)-Lycoricidine
and Seiichiro
Ogawa*
Faculty of Science and Technology,
Hiyoshi, Kohoku-ku,
Yokohama
Keio University,
223, Japan
Abstract: The stereoselecrive total synthesis of the ride compound mu-ring from D-glucoseis described. The key steps in this synthesis are Ferrier rearrangemenr to constt-WI the optically a-rive cyclohexenone (C-ring), and Pd.catalyzed intramolecular Heck reacrion fo build the phenanrhridone skeleron.
The phenanthridone
alkaloid family, (+)-lycoricidine
(l)‘, narciclasine2,
the attention because of their powerful antimitodc
and cytotoxic activities.
also reported
The strucmres
to possess
phenanthridone challenging, appeared
skeleton therefore,
so far.
lycoricidine
antiviral
activiry. 4
with four 01 six contiguous several reports
In this communication,
Pd-catalyzed
asymmetic
uiacetate
which
centers arc synthetically
the total SynthesesS
and synthetic
we wish to report the stereoselective
cyclization
(Heck
that the phenanthridone
(17) is
include
interesting
approaches6
total synthesis
reaction)’
skeleton might be effectively
of bromo-olefin
(10 or II),
four chira! centers could be prepared in a homochiral
enopyrauosidc
(4), which would be obtained stereoselectively
The known dial (2),9 prepared material.
(+I-Lycoficidine
of these compounds
attracted
the and have
of (+)-
(1) starring from D-glucose.
Our synthetic analysis suggested possessing
concerning
and pancraristatin3,
from D-glucose
The hydroxyl groups in 2 were protected
3 (90% yield) was treated
of 4 with mercuric
in 7 steps, was chosen as a starting ethers, and the resulting compound
to afford 5.enopyranoside
aifluoroacet.~e
4525
of 5-
from D-glucose.
stereoselectively
toluene
by
and the C-ring of lycoricidine
form utilizing Ferrier rearrangement8
as di-methoxymethyl
with DBU in refluxing
Catalytic Fenier rearrangement
constructed
(4) in 77% yield.
(1 mol %) in acetone-water
(r t (20 h)‘o
4526
OMOM
,
1 -
OMOM
-
MOM = -CH20Me MPM = -CH&$l&OMe) BL = -COPh ,”
(+)-Lycoricidine (1)
provided a cyclohexanone methanesulfonyl chiral centers
derivative
(5). Without purification,
chloride and uiethylamine corresponding
to give the cyclohexenone
to C-3, 4 and 4a of lycoricidine,
carbonyl group in 6 with NaBH4-CeCl3
compound
I1 in MeOH proceeded
5 was dehydrated
(6), which embodies
by the action of three contiguous
in 69% yield from 4.
Reduction
highly stereoselectively,
and compound
of the 7
4527
was obtained as a single product in 86% yield. The hydroxyl group in 7 was protected ether to give 8 in 60% yield. was then condensed
Reduction
of the azido group in 8 with LiAlH4 provided
with 6.bromopiperonylic
acid (18)12 under the conditions
an amide (10) in 89% overall yield from 8. With the bmmo-oiefin 10 was attempted
[Pd(OAc)2
reflu~j,‘~ however,
amide (11),‘5 quantitatively.
under the similar conditions treatment mol%),
and Tl(OAc)
Mirsunobu
stereochemistry
(2 equiv.)
reaction’9
in DMF
(20 mol %), 1,2-bis(diphenylphosphino)ethane at 140 OC for 48 h afforded
of 13 with benzoic
for (+)-lycoticidine
ally1 alcohol (15). Acid hydrolysis acetylation
(Ac20, pyridine)
to trifluoroacetic
acid generated
in 68% yield.
successfully
the product
Thus,
(DIPHOS)
(40
possessing
the
could be found in the reaction
the benzoate
(CHC13))
(14), possessing
the correct
The O~benzoyl group in 14 was deprotected
of O-MOM group in 15 (THl-aqueous
HCI), followed
to give the
by convendonal
afforded the triacetate (16)15 in 49% yield from compound 14. Exposure of 16
acid in CHC13 *O (rt, 2 h) removed the N-MPM group to afford (+I-lycoricidine
(17) in 53% yield. The spectral (1~ and 13C NMR) and physical propertics [a]$’
(II).
Removal of the O-MPM group in 12 (DDQ, wet CHZCI~)~~ afforded the ally1 alcohol (13) in 53%
mixture. yield.
derivative
of N&H to give the
reaction of 11 proceeded
skeleton (12) in 68 % yield. I5 I7 No other diasrereoisomers
phenanthridone
of
products and the starting
chloride in the presence
The crucial cyclization
cyclization
of modified Heck reaction recently reported by Grigg and co-workers.‘6
11 with Pd(OAc)2
of compound
aromatized
to give
(2 equiv) CH3CN,
reaction with the N-protected
The amide nitrogen in 10 was alkyiated with p-methoxybenzyl fully protected
protccol]3
(10) in hand, Pd-catalyzed
The unidentified
We then turned to try the cycliration
an amine (9), which
of Shioitis
(20 mol%), Ph3P (50 mol%), Et3N (2 equiv), Ag2CO3
no desired product was obtained.
material were isolated.
as ap-methoxybenzyl
of synthetic
17 were in good accordance
+ 214 ’ (CHCl3)t.
generate (+)-lycoricidine
Finally, 0-acetyl (I), quantitatively.
synthedc
specimen
reported
for the authentic
by PaulsenSc
+238 ’
{mp 236.237 ‘C,
group was removed by the treatment with MeONa in MeOH to Again, the spectral (IH and 13C NMR) and physical data of the
(mp 217-221 “C (dec), [a]$ compound
with those reported
triacetate
Imp 233-235 OC, [a]#
+199 ’ (pyridine))
imp 214.5-215.5
“C (dec),’
showed a good accordance
with those’
224-226 “C (dec),5C [a],$0
+ 180 ’
(pytidine)5C]. In summary, the stereoselective achieved.
This synthesis
rearrangement rings.
proceeded
should be very:seful
This approach
phenanthridone
total synthesis of (+)-lycoricidine
(lj starting from D-glucose has been
in 17 steps from the known compound for chiral syntheses
also proved that intramolecular
(2). and revealed
of natural products having substituted
Heck reaction is effective
that Fen&r cyclohexane
for the construction
of the
skeleton.
References
and
Notes
Y. Torii, Y. Isogai, Chem. Pharm. Bull., 16, 1860 (1968).
1.
T. Okamoto,
2.
G. Ceriotti, Nature, 213, 595 (1967); F. Piorzi, C. Fuganti, R. Mondelli, G. Ceriotti, Tetrahedron, 24, II19 (1968); C. Fuganti, M. Mazza, J. Chem. Sm., Chem. Commun., 239 (1972); A. Mondon, K. Krohn, Terrahedron Lat., 2085 (1972).
3.
G. R. Peffif, V. Gaddamidi, G. M. Cragg, D. L. Herald, Y. Sagawa, 1. Chem. S,x, Chm Commun., 1693 (1984); G. R. Petfit, V. Gaddamidi, G. M. Cragg, J. Nat. Prod., 47, 1018 (1984).
4.
B. G. Ugarkar, J. DaRe, E. M. Schubert, Synrhesis, 715 (1987).
4528
5.
Total synthesis of mcemic lycoricidine, see a) S. Ohm, S. Kimoto, Chrm. Pharm. Bull., 24.2971 (1976). b) see ref. 4. Chin11 and non-stenoselective total synthesis of (+)-lycoricidine startmg from Dglucose, see c) H. Paulsen, M. Srubbe, Liebigs Ann. Chem., 535 (1983); d) H. Paulsen, M. Stubbe, Tetruhednm Len., 23, 3171 (19X2). Total synthesis of racemic pancratistatin, see e) S. J. Danishefsky, Y. Lee, J. Am. Chem. Sot., 111, 4829 (1989).
6.
Synthetic approach to (+)-pancratistatin and rotz synthesis of (+)-tetrabenryliyco~cidine starting from L-arabinose, see a) R. C. Thompson and J. Kallmerten, J. Org. Chem., 55, 6076 (1990). Synthetic approach to (+)-pancratistatin utilizing chiral a-alkoxy imines, see b) R. D. Clark, M. Souchet, Tetrahedron Lett., 31, 193 (1990).
7.
For a review,
8.
R. J. Fenier, J. Chem. Sot., Perkin Trans. 1, 1455 (1979); R. Blattner, R. J. Fender, S. R. Hains, ibid., 2413 (1985).
see R. F. Heck, Ax.
R. Masse, Carbohydr.
Chem. Res., 12, 146 (1979).
9.
S. Hanessian,
10.
N. Chida, M. Ohtsuka, K. Ogura, S. Ogawa, Bull. Chem. Sot. Jpn., 64, (1991) in press. This catalytic Ferrier rearrangement has been utilized for the chiral synthesis of the aminocyclitol moiety of antibiotic hygromycin A, see N. Chida, M. Ohtsuka, K. Nakarawa, S. Ogawa, J. Org. Chem., 56, 2976 (1991).
Res., 35, 175 (1974).
II.
A. L. Gemal, J. -L. Luche, J. Am. Chem. SK,
103, 5454 (1981). J. Am. Chem. Sot., 77, 5885 (1955).
12.
H. M. Fales, E. W. Warnhoff,
13.
S. Yamada, Y. Kasai, T. Shioiri, Terrahedron Len., 1595 (1973).
14.
M. M. Abelman, T. Oh, L. E. Overman, J. Ory. Chem., 52, 4130 (1987); M. M. Abelman, Ovcnnan, V. D. Tran, J. Am. Chem. Sot., 112, 6959 (1990).
15.
All new compounds were characterized by 270 MHz 1H NMR, IR and mass spectromenic and/or elemental analyses. Selected spectml and physical data for 11: i~a]$ -141 ’ (c 0.25, CHC13); 1H NMR (CDCl3) 6 7.40 and 7.23 (2d, each 2H, J = 8.4 Hz), 6.90 (d, 2H, J = X.8 Hz), 6.85 (s, 2H), 6.82 (d, ZH, J = 8.8 Hz), 5.95 and 5.89 (2d, each lH, J = 1.3 Hz), 5.62 (s, 2H), 4.93 (d, IH, J = 15.2 Hz), 4.67 (m, IN), 4.65 (d, IH, J = 7.1 Hz), 4.59 (s, ZH), 4.53 (s, ZH), 4.28 (m, IH), 4.24 (d, 111, J = 15.2 Hz), 4.22 (d, IH, I = 7.1 Hz), 4.04 (dd, IH, 1 = 3.3 and 3.3 Hz), 3.80 and 3.80 (2s, each 3H), 3.72 (dd, lH, J = 9.5 and 1.5 Hz), 3.41 and 3.17 (Zs, each 3H). For 12: [a]$ -32’ (c 0.7, CHCl3); 1H NMR (CDCl3) 6 7.53 (s, lHj, 7.30 and 7.11 (2d, each lH, J = 8.8 Hz), 6.96 (s, IH), 6.89 and 6.X0 (2d, each lH, J =X.8 Hz), 6.02 and 6.01 (2d, each IH, J = 1.3 Hz), 5.99 (m, lH), 5.19 and 4.97 (2d, each IH, J = 16.1 Hz), 4.77 (s, 2H), 4.74 (d, lH, J =6.X Hz), 4.72 (m. IH), 4.67 and 4.59 (2d, each IH, J = 11.7 Hz), 4.49 (d, IH, J =6.X Hz), 4.37 (m, lH), 4.14 (m. IH), 3.99 (dd, IH, J = 7.7 and 1.8 Hz), 3.81 , 3.76, 3.3X and 3.38 (4s, each 3H). For 16: [a]$ +154 ’ (c 0.64, CHC13); ‘H NMR (CDC13) 6 7.62 (s, IH), 7.17 (d, 2H, J = 8.8 Hz), 6.89 (s, lH), 6.82 (d, 2H, 1 = 8.8 Hz), 6.06 and 6.05 (2d, each lH, J = 1.3 Hz), 5.96 (dd, IH, J = 2.9 and 1.5 Hz), 5.91 (dd, IH, J = 4.” and 2.6 Hz), 5.57 (ddd, IH, I = 7.0, 2.6 and 1.5 Hz), 5.45 (d, IH, J = 16.1 Hz), 5.12 (dd, IH, J = 7.0 and 2.6 Hz), 4.60 (d, lH, J = 16.1 Hz), 4.29 (ddd, IH, J = 4.0, 1.5 and 1.5 Hz), 3.77, 2.09, 2.05 and 1.88 (4s. each 3H).
16.
R. Grigg, V. Loganathan, (1991).
17.
When this reaction was carried out in the absence of TlOAc [Pd(OAc)2, (10 mol%), Ph3P (20 mol%), K2CO3 (1.5 equiv) in CH3CN (r&u, 4 days)], the cyclized product (12) was obtained in only 9% yield, along with the recovery (90%) of the starting material
1x.
K. Horita, T. Yoshioka, T. Tanaka, Y. Oikawa, 0. Yonemitsu,
19.
0. Mitsunobu,
20.
Neat, anhydrous trifluoroacetic acid had been used for a deprotcction of the amide-MPM group in the total synthesis of (+)-hitachimycin, see A. B. Smith, III, T. A. Ran”, N. Chida, G. A. Sulikowski, J. Org. Chew., 55, 1136 (1990).
Synrhesis,
W. C. Wildman,
V. Sanrhakumar,
V. Sridharan, A. Teasdale, Tetrahedron
Tetrahedron,
L. E.
Lert., 32,687
42, 3021 (1986).
1 (1981).
(Received in Japan 7 May 1991)
Noritaka
Department
Total Synthesis
Chida,
Masami
of Applied Chemisuy,
Ohtsuka,
of (+)-Lycoricidine
and Seiichiro
Ogawa*
Faculty of Science and Technology,
Hiyoshi, Kohoku-ku,
Yokohama
Keio University,
223, Japan
Abstract: The stereoselecrive total synthesis of the ride compound mu-ring from D-glucoseis described. The key steps in this synthesis are Ferrier rearrangemenr to constt-WI the optically a-rive cyclohexenone (C-ring), and Pd.catalyzed intramolecular Heck reacrion fo build the phenanrhridone skeleron.
The phenanthridone
alkaloid family, (+)-lycoricidine
(l)‘, narciclasine2,
the attention because of their powerful antimitodc
and cytotoxic activities.
also reported
The strucmres
to possess
phenanthridone challenging, appeared
skeleton therefore,
so far.
lycoricidine
antiviral
activiry. 4
with four 01 six contiguous several reports
In this communication,
Pd-catalyzed
asymmetic
uiacetate
which
centers arc synthetically
the total SynthesesS
and synthetic
we wish to report the stereoselective
cyclization
(Heck
that the phenanthridone
(17) is
include
interesting
approaches6
total synthesis
reaction)’
skeleton might be effectively
of bromo-olefin
(10 or II),
four chira! centers could be prepared in a homochiral
enopyrauosidc
(4), which would be obtained stereoselectively
The known dial (2),9 prepared material.
(+I-Lycoficidine
of these compounds
attracted
the and have
of (+)-
(1) starring from D-glucose.
Our synthetic analysis suggested possessing
concerning
and pancraristatin3,
from D-glucose
The hydroxyl groups in 2 were protected
3 (90% yield) was treated
of 4 with mercuric
in 7 steps, was chosen as a starting ethers, and the resulting compound
to afford 5.enopyranoside
aifluoroacet.~e
4525
of 5-
from D-glucose.
stereoselectively
toluene
by
and the C-ring of lycoricidine
form utilizing Ferrier rearrangement8
as di-methoxymethyl
with DBU in refluxing
Catalytic Fenier rearrangement
constructed
(4) in 77% yield.
(1 mol %) in acetone-water
(r t (20 h)‘o
4526
OMOM
,
1 -
OMOM
-
MOM = -CH20Me MPM = -CH&$l&OMe) BL = -COPh ,”
(+)-Lycoricidine (1)
provided a cyclohexanone methanesulfonyl chiral centers
derivative
(5). Without purification,
chloride and uiethylamine corresponding
to give the cyclohexenone
to C-3, 4 and 4a of lycoricidine,
carbonyl group in 6 with NaBH4-CeCl3
compound
I1 in MeOH proceeded
5 was dehydrated
(6), which embodies
by the action of three contiguous
in 69% yield from 4.
Reduction
highly stereoselectively,
and compound
of the 7
4527
was obtained as a single product in 86% yield. The hydroxyl group in 7 was protected ether to give 8 in 60% yield. was then condensed
Reduction
of the azido group in 8 with LiAlH4 provided
with 6.bromopiperonylic
acid (18)12 under the conditions
an amide (10) in 89% overall yield from 8. With the bmmo-oiefin 10 was attempted
[Pd(OAc)2
reflu~j,‘~ however,
amide (11),‘5 quantitatively.
under the similar conditions treatment mol%),
and Tl(OAc)
Mirsunobu
stereochemistry
(2 equiv.)
reaction’9
in DMF
(20 mol %), 1,2-bis(diphenylphosphino)ethane at 140 OC for 48 h afforded
of 13 with benzoic
for (+)-lycoticidine
ally1 alcohol (15). Acid hydrolysis acetylation
(Ac20, pyridine)
to trifluoroacetic
acid generated
in 68% yield.
successfully
the product
Thus,
(DIPHOS)
(40
possessing
the
could be found in the reaction
the benzoate
(CHC13))
(14), possessing
the correct
The O~benzoyl group in 14 was deprotected
of O-MOM group in 15 (THl-aqueous
HCI), followed
to give the
by convendonal
afforded the triacetate (16)15 in 49% yield from compound 14. Exposure of 16
acid in CHC13 *O (rt, 2 h) removed the N-MPM group to afford (+I-lycoricidine
(17) in 53% yield. The spectral (1~ and 13C NMR) and physical propertics [a]$’
(II).
Removal of the O-MPM group in 12 (DDQ, wet CHZCI~)~~ afforded the ally1 alcohol (13) in 53%
mixture. yield.
derivative
of N&H to give the
reaction of 11 proceeded
skeleton (12) in 68 % yield. I5 I7 No other diasrereoisomers
phenanthridone
of
products and the starting
chloride in the presence
The crucial cyclization
cyclization
of modified Heck reaction recently reported by Grigg and co-workers.‘6
11 with Pd(OAc)2
of compound
aromatized
to give
(2 equiv) CH3CN,
reaction with the N-protected
The amide nitrogen in 10 was alkyiated with p-methoxybenzyl fully protected
protccol]3
(10) in hand, Pd-catalyzed
The unidentified
We then turned to try the cycliration
an amine (9), which
of Shioitis
(20 mol%), Ph3P (50 mol%), Et3N (2 equiv), Ag2CO3
no desired product was obtained.
material were isolated.
as ap-methoxybenzyl
of synthetic
17 were in good accordance
+ 214 ’ (CHCl3)t.
generate (+)-lycoricidine
Finally, 0-acetyl (I), quantitatively.
synthedc
specimen
reported
for the authentic
by PaulsenSc
+238 ’
{mp 236.237 ‘C,
group was removed by the treatment with MeONa in MeOH to Again, the spectral (IH and 13C NMR) and physical data of the
(mp 217-221 “C (dec), [a]$ compound
with those reported
triacetate
Imp 233-235 OC, [a]#
+199 ’ (pyridine))
imp 214.5-215.5
“C (dec),’
showed a good accordance
with those’
224-226 “C (dec),5C [a],$0
+ 180 ’
(pytidine)5C]. In summary, the stereoselective achieved.
This synthesis
rearrangement rings.
proceeded
should be very:seful
This approach
phenanthridone
total synthesis of (+)-lycoricidine
(lj starting from D-glucose has been
in 17 steps from the known compound for chiral syntheses
also proved that intramolecular
(2). and revealed
of natural products having substituted
Heck reaction is effective
that Fen&r cyclohexane
for the construction
of the
skeleton.
References
and
Notes
Y. Torii, Y. Isogai, Chem. Pharm. Bull., 16, 1860 (1968).
1.
T. Okamoto,
2.
G. Ceriotti, Nature, 213, 595 (1967); F. Piorzi, C. Fuganti, R. Mondelli, G. Ceriotti, Tetrahedron, 24, II19 (1968); C. Fuganti, M. Mazza, J. Chem. Sm., Chem. Commun., 239 (1972); A. Mondon, K. Krohn, Terrahedron Lat., 2085 (1972).
3.
G. R. Peffif, V. Gaddamidi, G. M. Cragg, D. L. Herald, Y. Sagawa, 1. Chem. S,x, Chm Commun., 1693 (1984); G. R. Petfit, V. Gaddamidi, G. M. Cragg, J. Nat. Prod., 47, 1018 (1984).
4.
B. G. Ugarkar, J. DaRe, E. M. Schubert, Synrhesis, 715 (1987).
4528
5.
Total synthesis of mcemic lycoricidine, see a) S. Ohm, S. Kimoto, Chrm. Pharm. Bull., 24.2971 (1976). b) see ref. 4. Chin11 and non-stenoselective total synthesis of (+)-lycoricidine startmg from Dglucose, see c) H. Paulsen, M. Srubbe, Liebigs Ann. Chem., 535 (1983); d) H. Paulsen, M. Stubbe, Tetruhednm Len., 23, 3171 (19X2). Total synthesis of racemic pancratistatin, see e) S. J. Danishefsky, Y. Lee, J. Am. Chem. Sot., 111, 4829 (1989).
6.
Synthetic approach to (+)-pancratistatin and rotz synthesis of (+)-tetrabenryliyco~cidine starting from L-arabinose, see a) R. C. Thompson and J. Kallmerten, J. Org. Chem., 55, 6076 (1990). Synthetic approach to (+)-pancratistatin utilizing chiral a-alkoxy imines, see b) R. D. Clark, M. Souchet, Tetrahedron Lett., 31, 193 (1990).
7.
For a review,
8.
R. J. Fenier, J. Chem. Sot., Perkin Trans. 1, 1455 (1979); R. Blattner, R. J. Fender, S. R. Hains, ibid., 2413 (1985).
see R. F. Heck, Ax.
R. Masse, Carbohydr.
Chem. Res., 12, 146 (1979).
9.
S. Hanessian,
10.
N. Chida, M. Ohtsuka, K. Ogura, S. Ogawa, Bull. Chem. Sot. Jpn., 64, (1991) in press. This catalytic Ferrier rearrangement has been utilized for the chiral synthesis of the aminocyclitol moiety of antibiotic hygromycin A, see N. Chida, M. Ohtsuka, K. Nakarawa, S. Ogawa, J. Org. Chem., 56, 2976 (1991).
Res., 35, 175 (1974).
II.
A. L. Gemal, J. -L. Luche, J. Am. Chem. SK,
103, 5454 (1981). J. Am. Chem. Sot., 77, 5885 (1955).
12.
H. M. Fales, E. W. Warnhoff,
13.
S. Yamada, Y. Kasai, T. Shioiri, Terrahedron Len., 1595 (1973).
14.
M. M. Abelman, T. Oh, L. E. Overman, J. Ory. Chem., 52, 4130 (1987); M. M. Abelman, Ovcnnan, V. D. Tran, J. Am. Chem. Sot., 112, 6959 (1990).
15.
All new compounds were characterized by 270 MHz 1H NMR, IR and mass spectromenic and/or elemental analyses. Selected spectml and physical data for 11: i~a]$ -141 ’ (c 0.25, CHC13); 1H NMR (CDCl3) 6 7.40 and 7.23 (2d, each 2H, J = 8.4 Hz), 6.90 (d, 2H, J = X.8 Hz), 6.85 (s, 2H), 6.82 (d, ZH, J = 8.8 Hz), 5.95 and 5.89 (2d, each lH, J = 1.3 Hz), 5.62 (s, 2H), 4.93 (d, IH, J = 15.2 Hz), 4.67 (m, IN), 4.65 (d, IH, J = 7.1 Hz), 4.59 (s, ZH), 4.53 (s, ZH), 4.28 (m, IH), 4.24 (d, 111, J = 15.2 Hz), 4.22 (d, IH, I = 7.1 Hz), 4.04 (dd, IH, 1 = 3.3 and 3.3 Hz), 3.80 and 3.80 (2s, each 3H), 3.72 (dd, lH, J = 9.5 and 1.5 Hz), 3.41 and 3.17 (Zs, each 3H). For 12: [a]$ -32’ (c 0.7, CHCl3); 1H NMR (CDCl3) 6 7.53 (s, lHj, 7.30 and 7.11 (2d, each lH, J = 8.8 Hz), 6.96 (s, IH), 6.89 and 6.X0 (2d, each lH, J =X.8 Hz), 6.02 and 6.01 (2d, each IH, J = 1.3 Hz), 5.99 (m, lH), 5.19 and 4.97 (2d, each IH, J = 16.1 Hz), 4.77 (s, 2H), 4.74 (d, lH, J =6.X Hz), 4.72 (m. IH), 4.67 and 4.59 (2d, each IH, J = 11.7 Hz), 4.49 (d, IH, J =6.X Hz), 4.37 (m, lH), 4.14 (m. IH), 3.99 (dd, IH, J = 7.7 and 1.8 Hz), 3.81 , 3.76, 3.3X and 3.38 (4s, each 3H). For 16: [a]$ +154 ’ (c 0.64, CHC13); ‘H NMR (CDC13) 6 7.62 (s, IH), 7.17 (d, 2H, J = 8.8 Hz), 6.89 (s, lH), 6.82 (d, 2H, 1 = 8.8 Hz), 6.06 and 6.05 (2d, each lH, J = 1.3 Hz), 5.96 (dd, IH, J = 2.9 and 1.5 Hz), 5.91 (dd, IH, J = 4.” and 2.6 Hz), 5.57 (ddd, IH, I = 7.0, 2.6 and 1.5 Hz), 5.45 (d, IH, J = 16.1 Hz), 5.12 (dd, IH, J = 7.0 and 2.6 Hz), 4.60 (d, lH, J = 16.1 Hz), 4.29 (ddd, IH, J = 4.0, 1.5 and 1.5 Hz), 3.77, 2.09, 2.05 and 1.88 (4s. each 3H).
16.
R. Grigg, V. Loganathan, (1991).
17.
When this reaction was carried out in the absence of TlOAc [Pd(OAc)2, (10 mol%), Ph3P (20 mol%), K2CO3 (1.5 equiv) in CH3CN (r&u, 4 days)], the cyclized product (12) was obtained in only 9% yield, along with the recovery (90%) of the starting material
1x.
K. Horita, T. Yoshioka, T. Tanaka, Y. Oikawa, 0. Yonemitsu,
19.
0. Mitsunobu,
20.
Neat, anhydrous trifluoroacetic acid had been used for a deprotcction of the amide-MPM group in the total synthesis of (+)-hitachimycin, see A. B. Smith, III, T. A. Ran”, N. Chida, G. A. Sulikowski, J. Org. Chew., 55, 1136 (1990).
Synrhesis,
W. C. Wildman,
V. Sanrhakumar,
V. Sridharan, A. Teasdale, Tetrahedron
Tetrahedron,
L. E.
Lert., 32,687
42, 3021 (1986).
1 (1981).
(Received in Japan 7 May 1991)