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Enantiospecific synthesis of D-daunosamine from thioglycolic acid
Tetrahedron: Asymmefry Vol. 5, No. 10, pp. 1869-1872,1994 Blsevier ScienceLtd Printed in Gnat Britain 0957-416&94$7.oottl.o0
0957-4 166(94)00258-4
Enantiospecific Synthesis of D-Daunosamine Thioglycolic Acid
from
Shy-Yau PO and Biing-Jiun Uang* Department of Chemistry, National Tsing Hua University Hsinchu, Taiwan 30043, Republic of China
Abstract: A highly stereocontmlled enantiospecific synthesis of Ddaunosamine in six steps through a diastereoselective
C-C bond formation and a stereocontrolled
cis-dihydxoxylation
reaction
employing chiral 1,3-oxathiolan-5-one as a chiial acetate equivalent is described. L-Daunosamine,
L-ristosamine,
and L-acosamine
are the glycosidic
components
of a number of
important anthracycline antibiotics that exhibit impressive activity against a broad range of solid tumors and soft tissue sarcomas.
The importance
of the anthracycline
antibiotics
as antineoplastic
associated need for large quantities of these 2,3,6-trideoxy-3-aminohexopyranoses
agents and the
for structure-activity
studies have been major factors contributing to the strong synthetic interest in these sugars.1 We have reported enantioselective camphor
syntheses of a-substituted
thioglycolic acids from thioglycolic acid employing (lR)-(+)-
as the chiral auxiliary with high degree of asymmetric
enantiospecific
induction.2-3
Herein we report an
synthesis of D-daunosamine from thioglycolic acid through chiral 1,3-oxathiolan-5-one
1,
prepared from the condensation of thioglycolic acid with ( 1R)-(+)-camphor,2 as a chiral acetate equivalent. Deprotonation of 1,3-oxathiolan-5-one N-benzenesulfonylcrotyl
1 with lithium diisopropylamide followed by condensation with
imine 2 in tetrahydrofuran
gave three diastereomeric
products 3a-c in a ratio of
35:1.5:1. The assignment of the isomers was based on the chelation model4 and our previous experience2Js5 at this stage. Interestingly,
when the major isomer 3a was subjected to an osmium tetraoxide catalyzed cis-
dihydroxylation6 a single y-lactone 4 was obtained in 65% yield with quantitative recovery of camphor. When 6c was treated under similar reacuon condition, two isomeric y-lactones 5 and 6 were obtained in a ratio of 2.9 to 1. Lactones 4 and 5 were found to have identical 1H NMR and t3C NMR spectra. They showed similar
3a X=NHS$Ph,Y=H 3c X=H,Y=NHS02Ph
3b
1870
S.-Y. PO and B.-J.
UANG
magnitude of specific rotations however with opposite sign.7 This information suggested that lactones 4 and 5 were enantiomers. The H3-H4 coupling constant (J) for lactone 5 is 4.2 Hz, and for lactone 6 is 8.6 Hz. The H3-H4 coupling constants for lactones 7 and 8 were 3.52 Hz and 7.26 Hz rtspectively.8
Since lactones 4-8
a~ similar in structure.lactones 4 and 5 having a smaller coupling constant were assigned to the rruns product and lactone 6 having a larger coupling constant was assigned to the cis product. It is notable thatunder the cisdihydroxylation condition not only the double bond was hydroxylated but also the oxathioianone ring was opened and the C2-S bond was cleaved!
0s04, NM0 THF / Hz0 65%
3a
/’ 0
0
JH3_H4= 4.2 Hz 5
3c
( 2.9 : 1 )
J H3_~.,= 8.6 Hz 6
0
P
I-b!& H\‘
H3
iHCOPh
H
Jw_H4 = 3.52 Hz 7
JH3_,,.,= 7.26 Hz 8
The formation of a single y-lactone 4 from 3a presumably followed the pathway as depicted in scheme II. The sulfur atom was oxidized to sulfoxide from the less hindered face. The sulfoxide moiety directed the cis-dihydroxylation of osmium tetraoxide on the olefin stereospecitically with the most stable conformer of 3a, namely A* where the conformation is locked by an intramolecular hydrogen bonding and the propenyl group is away from the sterically congested bomane moiety, to produce a single osmate. The sulfoxide was then further oxidized to sulfone. Decomposition of the osmate followed by an intramolecular lactone transformation to released camphor and sulfur dioxide gave the y-lactone 4. Indeed, camphor was recovered after workup the reaction. Whereas on the formation of y-lactones 5 and 6 from 3c. there are two more stable _ conformers Bt and Cz for the cis-dihydroxylation. Although B* is stabilized by an intramolecular hydrogen bonding, however the propenyl moiety is closer to the sterically congested bomane moiety and therefore
D-Daunosamine
from thioglycolic
1871
acid
makes B* and C* relatively closer in stability. Thus the reaction could undergo on either side of the olefin to produce two products in a ratio of 2.9 to 1
oso, NM0
HSOzPh
PhSO&
L
Reduction of lactone 4 with DIBAL9 in tetrahydrofuran yield.
Treatment
hexopyranose reaction
of the lactol 9 with Amberlite
1Oa and lob in >99% yield with a ratio of 1:3. Treatment
condition
of methyl P-L-daunosaminidelu
with benzenesulfonyl
1Oa and lob were anomeric chloride/ triethylamine
gave the
11. The tH NMR spectra of lob and 11 were
methyl P-L-N-benzenesulfonyldaunosaminide
found to be identical after careful examination
lactol9 in 96%
gave two isomeric
of 1Oa or lob under the same
each gave the same mixture of 10a and lob. Therefore
isomers. N-Sulfonation corresponding
at -78oC gave the corresponding
CG120 ( H+ form ) in methanol
of these spectra. The specific rotation of lob is -6.O(c 0.5,
CHCl3), whereas the specific rotation of 11 is +5.7(c 2, CHC13). Therefore lob and 11 were enantiomers. In other words lob is the P-D-N-benzenesulfonyldaunosaminide. intermediates
were thus confiied.
Our previous assignments
Removal of the N-benzenesulfonyl
for all important
group could be achieved by treating
lob or 11 with sodium in liquid ammonia in 98% yield Thus a concise, trideoxyhexopyranose demonstrated.
highly stereocontrolled, from thioglycolic
If one starts a synthesis
and enantiospecific
acid employing
synthesis
(lR)-(+)-camphor
with (lS)-(-)-camphor
of optically
active D-2,3,6-
as the chiral auxiliary has been
as the chiral template,
one would finish the
1872
S.-Y. PO and B.-J. UANO
synthesis with L-sugar. The advanced intermediate 4 could also be transformed to other 2.3,~trideoxyhexop~anose.lt.12
13b:13a(P:a)=3
: 1 ’ 14 [a]o +5.7
13b [alo -6.0
Acknowledgment: This work was supported under Grant No. NSC 81-0~8-M~~78 by the National Science Council, Republic of China. We also thank the China Camphor Co. for free (lR)-(+)-camphor. References and Notes: 1. Hauser, F.M.; Ellenberger, aminohexopyranose
S.R. Chem. Rev. 1986,86,
35.; For the synthesis of 2,3,6-trideoxy-3-
see: Herczegh, P.; Zsely, M.; Kovacs, I.; Bat@ G.; Sztaricskai, F.J.; Tetrahedron
Lerr. 1990,32, 1195.; Dai, L.-x.; Lou, B.-l.; Zhang, Y.-z. J. Am. Chem. Sot. 1988,f10, 5195, and
references cited therein. 2.
Liu, H.H.; Chen. E.N.; Uang, B.J.; Wang, S.L. Tetrahedron Lett. 1990,31, 257.
3.
PO, S.Y.; Liu, H.H.; Uang, B.J. Tetrahedron:Asymmetr
4.
Heathcock, C-H. in “Asymmetric
5.
Press, Inc. For compound with a structure i has an R group on the a-face, a
1990, I, 143.
Synthesis” Morrison, J.D. ed., 1984, vol. 3, chapter 2, Academic and Hendo will
show lower proton chemical shift as compared with the corresponding compound with a P-R group. The proton chemical shifts of I&& and I$ in 3a and 3c are S 1.82,4.01, and 1.83,4.21 respectively. Whemas in 3b, &a 6 2.00 and 4.33 in its *H NMR spectrum. 6. 7.
I
and I& appeared at %
%
i
Hauser, F.M.; Ellenberger, S.R.; Clardy, J.C.; Bass, L.S. J. Am. C&n. Sot. 1984,106, Lactone 4, [a]~~~ +12.9 (c 1.74, C2HsOH); Lactone 5, [u]@ -11.6 fc 0.48, QH@H).
2458.
8. Hauser, F.M.; Rhee, R.P. J. Org. Chem. 1981,46, 227. 9. Hirama, M.; ho, S. Hererocycles 1989,28, 1229 and references cited therein. 10. Methyl &L-daunosaminide hydrochloride was purchased from Sigma Chemical Company, St. Louis, Missouri, U.S.A. 11. Fronza, G.; Fuganti, C!.; Grasselli, P. J. Chem. Sot., Chem. Commun. 1980, 442. 12. Wovkulich, P.M.; Uskokovic. M.R. J. Am. Chem. Sot. 1981,103, 3956.;idem Tetrahedron 41, 3455. (Received in Japan 16 June 1994, accepted 8 August 1994)
1985,
0957-4 166(94)00258-4
Enantiospecific Synthesis of D-Daunosamine Thioglycolic Acid
from
Shy-Yau PO and Biing-Jiun Uang* Department of Chemistry, National Tsing Hua University Hsinchu, Taiwan 30043, Republic of China
Abstract: A highly stereocontmlled enantiospecific synthesis of Ddaunosamine in six steps through a diastereoselective
C-C bond formation and a stereocontrolled
cis-dihydxoxylation
reaction
employing chiral 1,3-oxathiolan-5-one as a chiial acetate equivalent is described. L-Daunosamine,
L-ristosamine,
and L-acosamine
are the glycosidic
components
of a number of
important anthracycline antibiotics that exhibit impressive activity against a broad range of solid tumors and soft tissue sarcomas.
The importance
of the anthracycline
antibiotics
as antineoplastic
associated need for large quantities of these 2,3,6-trideoxy-3-aminohexopyranoses
agents and the
for structure-activity
studies have been major factors contributing to the strong synthetic interest in these sugars.1 We have reported enantioselective camphor
syntheses of a-substituted
thioglycolic acids from thioglycolic acid employing (lR)-(+)-
as the chiral auxiliary with high degree of asymmetric
enantiospecific
induction.2-3
Herein we report an
synthesis of D-daunosamine from thioglycolic acid through chiral 1,3-oxathiolan-5-one
1,
prepared from the condensation of thioglycolic acid with ( 1R)-(+)-camphor,2 as a chiral acetate equivalent. Deprotonation of 1,3-oxathiolan-5-one N-benzenesulfonylcrotyl
1 with lithium diisopropylamide followed by condensation with
imine 2 in tetrahydrofuran
gave three diastereomeric
products 3a-c in a ratio of
35:1.5:1. The assignment of the isomers was based on the chelation model4 and our previous experience2Js5 at this stage. Interestingly,
when the major isomer 3a was subjected to an osmium tetraoxide catalyzed cis-
dihydroxylation6 a single y-lactone 4 was obtained in 65% yield with quantitative recovery of camphor. When 6c was treated under similar reacuon condition, two isomeric y-lactones 5 and 6 were obtained in a ratio of 2.9 to 1. Lactones 4 and 5 were found to have identical 1H NMR and t3C NMR spectra. They showed similar
3a X=NHS$Ph,Y=H 3c X=H,Y=NHS02Ph
3b
1870
S.-Y. PO and B.-J.
UANG
magnitude of specific rotations however with opposite sign.7 This information suggested that lactones 4 and 5 were enantiomers. The H3-H4 coupling constant (J) for lactone 5 is 4.2 Hz, and for lactone 6 is 8.6 Hz. The H3-H4 coupling constants for lactones 7 and 8 were 3.52 Hz and 7.26 Hz rtspectively.8
Since lactones 4-8
a~ similar in structure.lactones 4 and 5 having a smaller coupling constant were assigned to the rruns product and lactone 6 having a larger coupling constant was assigned to the cis product. It is notable thatunder the cisdihydroxylation condition not only the double bond was hydroxylated but also the oxathioianone ring was opened and the C2-S bond was cleaved!
0s04, NM0 THF / Hz0 65%
3a
/’ 0
0
JH3_H4= 4.2 Hz 5
3c
( 2.9 : 1 )
J H3_~.,= 8.6 Hz 6
0
P
I-b!& H\‘
H3
iHCOPh
H
Jw_H4 = 3.52 Hz 7
JH3_,,.,= 7.26 Hz 8
The formation of a single y-lactone 4 from 3a presumably followed the pathway as depicted in scheme II. The sulfur atom was oxidized to sulfoxide from the less hindered face. The sulfoxide moiety directed the cis-dihydroxylation of osmium tetraoxide on the olefin stereospecitically with the most stable conformer of 3a, namely A* where the conformation is locked by an intramolecular hydrogen bonding and the propenyl group is away from the sterically congested bomane moiety, to produce a single osmate. The sulfoxide was then further oxidized to sulfone. Decomposition of the osmate followed by an intramolecular lactone transformation to released camphor and sulfur dioxide gave the y-lactone 4. Indeed, camphor was recovered after workup the reaction. Whereas on the formation of y-lactones 5 and 6 from 3c. there are two more stable _ conformers Bt and Cz for the cis-dihydroxylation. Although B* is stabilized by an intramolecular hydrogen bonding, however the propenyl moiety is closer to the sterically congested bomane moiety and therefore
D-Daunosamine
from thioglycolic
1871
acid
makes B* and C* relatively closer in stability. Thus the reaction could undergo on either side of the olefin to produce two products in a ratio of 2.9 to 1
oso, NM0
HSOzPh
PhSO&
L
Reduction of lactone 4 with DIBAL9 in tetrahydrofuran yield.
Treatment
hexopyranose reaction
of the lactol 9 with Amberlite
1Oa and lob in >99% yield with a ratio of 1:3. Treatment
condition
of methyl P-L-daunosaminidelu
with benzenesulfonyl
1Oa and lob were anomeric chloride/ triethylamine
gave the
11. The tH NMR spectra of lob and 11 were
methyl P-L-N-benzenesulfonyldaunosaminide
found to be identical after careful examination
lactol9 in 96%
gave two isomeric
of 1Oa or lob under the same
each gave the same mixture of 10a and lob. Therefore
isomers. N-Sulfonation corresponding
at -78oC gave the corresponding
CG120 ( H+ form ) in methanol
of these spectra. The specific rotation of lob is -6.O(c 0.5,
CHCl3), whereas the specific rotation of 11 is +5.7(c 2, CHC13). Therefore lob and 11 were enantiomers. In other words lob is the P-D-N-benzenesulfonyldaunosaminide. intermediates
were thus confiied.
Our previous assignments
Removal of the N-benzenesulfonyl
for all important
group could be achieved by treating
lob or 11 with sodium in liquid ammonia in 98% yield Thus a concise, trideoxyhexopyranose demonstrated.
highly stereocontrolled, from thioglycolic
If one starts a synthesis
and enantiospecific
acid employing
synthesis
(lR)-(+)-camphor
with (lS)-(-)-camphor
of optically
active D-2,3,6-
as the chiral auxiliary has been
as the chiral template,
one would finish the
1872
S.-Y. PO and B.-J. UANO
synthesis with L-sugar. The advanced intermediate 4 could also be transformed to other 2.3,~trideoxyhexop~anose.lt.12
13b:13a(P:a)=3
: 1 ’ 14 [a]o +5.7
13b [alo -6.0
Acknowledgment: This work was supported under Grant No. NSC 81-0~8-M~~78 by the National Science Council, Republic of China. We also thank the China Camphor Co. for free (lR)-(+)-camphor. References and Notes: 1. Hauser, F.M.; Ellenberger, aminohexopyranose
S.R. Chem. Rev. 1986,86,
35.; For the synthesis of 2,3,6-trideoxy-3-
see: Herczegh, P.; Zsely, M.; Kovacs, I.; Bat@ G.; Sztaricskai, F.J.; Tetrahedron
Lerr. 1990,32, 1195.; Dai, L.-x.; Lou, B.-l.; Zhang, Y.-z. J. Am. Chem. Sot. 1988,f10, 5195, and
references cited therein. 2.
Liu, H.H.; Chen. E.N.; Uang, B.J.; Wang, S.L. Tetrahedron Lett. 1990,31, 257.
3.
PO, S.Y.; Liu, H.H.; Uang, B.J. Tetrahedron:Asymmetr
4.
Heathcock, C-H. in “Asymmetric
5.
Press, Inc. For compound with a structure i has an R group on the a-face, a
1990, I, 143.
Synthesis” Morrison, J.D. ed., 1984, vol. 3, chapter 2, Academic and Hendo will
show lower proton chemical shift as compared with the corresponding compound with a P-R group. The proton chemical shifts of I&& and I$ in 3a and 3c are S 1.82,4.01, and 1.83,4.21 respectively. Whemas in 3b, &a 6 2.00 and 4.33 in its *H NMR spectrum. 6. 7.
I
and I& appeared at %
%
i
Hauser, F.M.; Ellenberger, S.R.; Clardy, J.C.; Bass, L.S. J. Am. C&n. Sot. 1984,106, Lactone 4, [a]~~~ +12.9 (c 1.74, C2HsOH); Lactone 5, [u]@ -11.6 fc 0.48, QH@H).
2458.
8. Hauser, F.M.; Rhee, R.P. J. Org. Chem. 1981,46, 227. 9. Hirama, M.; ho, S. Hererocycles 1989,28, 1229 and references cited therein. 10. Methyl &L-daunosaminide hydrochloride was purchased from Sigma Chemical Company, St. Louis, Missouri, U.S.A. 11. Fronza, G.; Fuganti, C!.; Grasselli, P. J. Chem. Sot., Chem. Commun. 1980, 442. 12. Wovkulich, P.M.; Uskokovic. M.R. J. Am. Chem. Sot. 1981,103, 3956.;idem Tetrahedron 41, 3455. (Received in Japan 16 June 1994, accepted 8 August 1994)
1985,