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Model studies directed toward microalga polyether macrolides: A route to 12-carbon tetrahydrofuran and tetrahydropyran subunits
Tetrahedron Letters,Vo1.30,No.Z8,pp Printed in Great Britain
3725-3728,1989 Maxwell
0040-4039/89 $3.00 + .OO Pergamon Macmillan plc
MODEL STUDIES DIRECTED TOWARD MICROALGA POLYETHER MACROLIDES: A ROUTE TO 12-CARBON TETRAHYDROFURAN
AND TETRAHYDROPYRAN
SUBUNITS
Miguel Zgrraga, Matias L. Rodriguez,' Catalina Ruiz-Pbrezl and Sulio D. Martin.* Centro
de Productos Naturales Orginicos Antonio Gonzalez,
Laguna-C.S.I.C.,
Carretera
de La Esperanza 2,
38206 La
Universidad de La Laguna,
Tenerife,
Spain. A new synthetic strategy for the regio- and stereo-specific SUMMARY: of heterosubstituted tetrahydrofuran and tetrahydropyran synthesis systems involving intramolecular iodoetherification of 2,3-epoxy-cycloalkenols were stereochemical studied. Unambiguous assignments are available from X-ray studies. The realization of convergent total syntheses of the recently found toxic marine polyether macrolides,
prorocentrolide2
malides' ) requires coordinated solutions to the furan
and -pyran systems.
or fijianolidesa
functionalized
cyto(lauli-
tetrahydro-
Our present strategy for these polyether building
blocks has emerged from a combination of studies on the conformational
prefe-
rences
chiral
and
stereoselective
epoxidation reported'
reactions of macrocycles ', and
methodology using adjacent hydroxyl groups.6 that
current
We
have
Sharpless asymmetric epoxidation of medium-size
cycloalkenols provided a single epoxide with the stereochemistry eq
1.
To
recently
allylic
Z-
indicated in
address the problem of marine macrolide po1yethe.r syntheses,
we
reasoned that a related macrocycle extended with an E-double bond at C5 could adopt
the
tically, double
local conformation 1 that is free of exo-ring closure
bond,
hydroxyl
would
occur
units
2 (es 2).
strain.
Theore-
induced by peripheral electrophilic attack at the by internal nucleophilic
group to give cis--a,a' -dialkylated
epoxide oxygen participation
torsional
participation
tetrahydropyrans 2,
of
the
or by
the
to yield trans-a,aI -dialkylated tetrahydrofuran
Herein we report on applications of these
principles
E’
Eq 1
3725
2
that
Eq 2
The vely
reaction
of 1 with
epoxide
mined
15
(Scheme
by X-raycrystallographic
The more
yields,
polar
1 upon
epoxy-alcohol products
were The
obtained
ring
accord
which base from
with
homologues
compounds the
and
with
quantitatively
(mp 136'C)
was
to
deter-
(%')." cyclization
reactions
on
33% -16 and -17 (30 and converted into the starting
the iodohydrins
are quantitatively (K,COa,
aq
acetone).
No
cyclization
the iodohydrin of -17 was gave
structures the
of u
stereoselecti-
O-hydroxy-13-oxabicyclo
converted
iodine-assisted
treatment
stereochemistry
analysis.g All new in
in both
respectively
respectively),
was
stereochemistry analysis
components
correspond
1 and 8,
ment.
The
3).
2,11-diiodo-1 which
(54% yield),
(2)
proceeded
cat/C-25"C,
product,
as the major
to afford,
[7.3.lltridec-5-ene the
12/Ti(Pri0)4
total
long treat-17 after Iz/Ti(PriO), crystallographic X-ray determined by
spectroscopic'* shown.
synthesis
Extension
and analytical of this
data
strategy
of fijianolide-A.3'4 are
higher
continuing.
of this work by DGICT through grant Support ACKNOWLEDGEMENTS: thanks and CAICYT grant 1184-84 is gratefully acknowledged. M.Z. tuto de Cooperaci6n Iberoamericana (Madrid) for a fellowship. REFERENCES
to
entirely
PB86-0608 the Insti-
AND NOTES
1.
to whom correspondence related with the X-ray analysis should be Authors adressed. 110, 7876 (1988). J.Am.Chem.Soc., M. Murata, T. Yasumoto, K, Torigoe, Y. Kakou, P. Crews, J.Org.Chem., 53, 3642 (1988). ;: E. Quifioa, P.J. Scheuer, J.Org.Chem., B, 3644 Herb, R.E. Moore, Corley, R. 4. D. (1988). 108, 2105 (1986). (b) S.L. Still, A.G. Romero, J.Am.Chem.Soc., 5. (a) W.C. B. Hulin, G. Shulte, J.Am.Chem.Soc., 10&, 2106 Sammakia, Schreiber, T. (c) W.C. Still, I. Galynker, Tetrahedron, 21, 3981 (1981) and (1986). references cited therein. A.W.M. Lee, V.S. Martin, M. Behrens, T. Katsuki, Sharpless, C.H. 6. K.B. 589 Takatani, S.M. Viti, F.J. Walker, S.S. Woodard, Pure App l.Chem., 55, Manta, J.D. Martin, Alvarez E. Let; a, 2093 (1988). M.L.iiguez, C. Ruiz-Phrez, Martin, 2097 (19881. Tetrahedron Lett., M. Kugamai, J. Soo Lee, T. Yasumoto, 8. (aj Mi .Murata, 5869 (1987). (b) Y.Y. Lin, M. Risk, S-M. Ray, D.V. Engen, J. Clardy, 28, J. Golik, J.C. James, K. Nakanishi, J.Am.Chem.Soc., 103, 6773 (1981). (c) H.N. Chou, H. Bando, G.V. Duyne, J. Clardy, J.Am.Chem.Soc., Y. Shimizu, 7.
3728
108, 514 (1986). 9. Unpublished results. orthorhombic, space group Fdd2, 10. Crystal data for 10: C12HltI202, 43.570 (341, b=32.7_61 (IL), c=8.584 (3) ii; V=12104 A3, Z=32. Data we:: AED computer-controlled Siemens four circle collected on a diffractometer, with GuKa graphite monochromated radiation. Of 2354 measured independent reflections. 2027 with Ia20 (I) were considered as The structure was solved by Patterson method (SHELXS-86) and observed. sucessive Fourier synthesis (XRAY-80): An empirical absorption correction was performed (DIFABS). Hvdroaen for carbon atoms olaced in calculated with anisotropic iodine atoms, Full matrix I..s”. refinement, positions. for isotropic carbon and oxygen atoms and fixed isotropic contribution hydrogens. Final R=0.077. 11. Crystal data for x: orthorhogbic, spacg group P 21/n, a= C12H,aI202, 8.428 (16), b=24.299 (76), c=l4.052 (60) A; V=2877 A3, Z=B. Of 3247 2665 with 1220(I) were considered as independent reflections, measured The structure was solved and refined as above. Final R=O.O76. observed. The details for both crystal structures will be given in a full paper. 12. 'H- and 'SC NMR spectra of selected compounds follow. 6: 'H NMR (CDC13) a5.82(1H, ddd, 5~10.5, 8.0, 8.0 Hz), 5.36(5H, m), 4.33TlH, m), 2.SS(lH, 7.4, 7.~3~z~idf."O~~~,o~~j J=:~95j(~j5 Hz); 13C NMR (CDC13) ddd, J=15.5, 128.0(d), 65.1(d), a135.1(d),3;3;iWjd), 29.6(i), 2&0(t)' 22.;(t). +:'H iMR (Cm131 s5.32(4H, 37*1(t), did, J=l4.0, 8.2, I.; Hz), 3.30TC3H, ddd, J=9.8, 4.5, 4.5 3.42(C& J=8.2 4.5 Hz)* 13C NMR (CDC13) 6131 7(d) 130 9(d) 128r9(~j~7i~t";cd~d~66.3(d~~ 61 l(d)' 58 O(d) 35 l(t) 3; l(tj 28*0(t)' '3.6;(CzH'br d J&O.: Hz)' 22.1(t). IO: 'H NhR (CDC13jS4.03(C1; br's) 3.79(C3H, ddd, J=lO.6, 7.5, 7.3 Hz) !?.06(C6Ha, ddd, Ji13.6' 7.5 7.4 Hzj 2.9l(C4Hb, ddd, J=13.6, 7.4, 7.3 Hzj, 4.27(CsH, ddd, J=I2.0: 7.4: 7.4 Hz) ;.;'A;;", ddd, J=l2.0, 12.0, 4.0 Hz), 2.34(C7Ha, dddd, J=I3.5, 12.0, 3.0, * 2.48(C7Hb, a) 2.97(CsHa m) 1.72(CaHb, m), 5.2O(CsH, ddd, J= 11.4, l;.O, 2.6 Hz), 5.iO(C,oH, dd:, JLIl.0,
'H NMR (CDCls! 64.O(C1H, m), 3.53(CzH, d, 5=2-O Hz), 4.48(CjH, ddd, J=4.0 2.4, 2.0 Hz), 3.55(CsH, ddd, J=9.6, 9.6, 1.3 Hz), 4.0(CsH, m), 5.4(CsH, '3C NMR (CDC13)a 74.O(Cl) 7O.O(C2) 31 9(C3) 38 5(C4) ~~:,~$'"3~'I~~b) 43 l(C7) 29 7(C8) 12; 8(C9) I;2 4.iCl0) '22 t(W) 27.4(Cl2j.x: 'H NkR (iDC1&3.;(C,H,'m), :.8(&i, m); 3.50tCsH; dd, JL 10.5, 1.7 Hz), 3.2(CaH, m), 3.78(CsH, ddd, J=l3.2, 10.3, 3.0 Hz). 2: 'H NMR (CDC13) 6 3.80(ClH, CzH, m), 4.58(CjH, ddd, J=9.9, 3.5, 3.5 Hz), g.Tz (CJHa, ddd, J=l5.1, 8.9, 3.5 Hz), 2.78(C4Hb, dd, J=15.1, 2.6 Hz), . (CsH, CsH, m), 5.56 (CaH, CloH, m). (Received in UK 11 May 1989)
3725-3728,1989 Maxwell
0040-4039/89 $3.00 + .OO Pergamon Macmillan plc
MODEL STUDIES DIRECTED TOWARD MICROALGA POLYETHER MACROLIDES: A ROUTE TO 12-CARBON TETRAHYDROFURAN
AND TETRAHYDROPYRAN
SUBUNITS
Miguel Zgrraga, Matias L. Rodriguez,' Catalina Ruiz-Pbrezl and Sulio D. Martin.* Centro
de Productos Naturales Orginicos Antonio Gonzalez,
Laguna-C.S.I.C.,
Carretera
de La Esperanza 2,
38206 La
Universidad de La Laguna,
Tenerife,
Spain. A new synthetic strategy for the regio- and stereo-specific SUMMARY: of heterosubstituted tetrahydrofuran and tetrahydropyran synthesis systems involving intramolecular iodoetherification of 2,3-epoxy-cycloalkenols were stereochemical studied. Unambiguous assignments are available from X-ray studies. The realization of convergent total syntheses of the recently found toxic marine polyether macrolides,
prorocentrolide2
malides' ) requires coordinated solutions to the furan
and -pyran systems.
or fijianolidesa
functionalized
cyto(lauli-
tetrahydro-
Our present strategy for these polyether building
blocks has emerged from a combination of studies on the conformational
prefe-
rences
chiral
and
stereoselective
epoxidation reported'
reactions of macrocycles ', and
methodology using adjacent hydroxyl groups.6 that
current
We
have
Sharpless asymmetric epoxidation of medium-size
cycloalkenols provided a single epoxide with the stereochemistry eq
1.
To
recently
allylic
Z-
indicated in
address the problem of marine macrolide po1yethe.r syntheses,
we
reasoned that a related macrocycle extended with an E-double bond at C5 could adopt
the
tically, double
local conformation 1 that is free of exo-ring closure
bond,
hydroxyl
would
occur
units
2 (es 2).
strain.
Theore-
induced by peripheral electrophilic attack at the by internal nucleophilic
group to give cis--a,a' -dialkylated
epoxide oxygen participation
torsional
participation
tetrahydropyrans 2,
of
the
or by
the
to yield trans-a,aI -dialkylated tetrahydrofuran
Herein we report on applications of these
principles
E’
Eq 1
3725
2
that
Eq 2
The vely
reaction
of 1 with
epoxide
mined
15
(Scheme
by X-raycrystallographic
The more
yields,
polar
1 upon
epoxy-alcohol products
were The
obtained
ring
accord
which base from
with
homologues
compounds the
and
with
quantitatively
(mp 136'C)
was
to
deter-
(%')." cyclization
reactions
on
33% -16 and -17 (30 and converted into the starting
the iodohydrins
are quantitatively (K,COa,
aq
acetone).
No
cyclization
the iodohydrin of -17 was gave
structures the
of u
stereoselecti-
O-hydroxy-13-oxabicyclo
converted
iodine-assisted
treatment
stereochemistry
analysis.g All new in
in both
respectively
respectively),
was
stereochemistry analysis
components
correspond
1 and 8,
ment.
The
3).
2,11-diiodo-1 which
(54% yield),
(2)
proceeded
cat/C-25"C,
product,
as the major
to afford,
[7.3.lltridec-5-ene the
12/Ti(Pri0)4
total
long treat-17 after Iz/Ti(PriO), crystallographic X-ray determined by
spectroscopic'* shown.
synthesis
Extension
and analytical of this
data
strategy
of fijianolide-A.3'4 are
higher
continuing.
of this work by DGICT through grant Support ACKNOWLEDGEMENTS: thanks and CAICYT grant 1184-84 is gratefully acknowledged. M.Z. tuto de Cooperaci6n Iberoamericana (Madrid) for a fellowship. REFERENCES
to
entirely
PB86-0608 the Insti-
AND NOTES
1.
to whom correspondence related with the X-ray analysis should be Authors adressed. 110, 7876 (1988). J.Am.Chem.Soc., M. Murata, T. Yasumoto, K, Torigoe, Y. Kakou, P. Crews, J.Org.Chem., 53, 3642 (1988). ;: E. Quifioa, P.J. Scheuer, J.Org.Chem., B, 3644 Herb, R.E. Moore, Corley, R. 4. D. (1988). 108, 2105 (1986). (b) S.L. Still, A.G. Romero, J.Am.Chem.Soc., 5. (a) W.C. B. Hulin, G. Shulte, J.Am.Chem.Soc., 10&, 2106 Sammakia, Schreiber, T. (c) W.C. Still, I. Galynker, Tetrahedron, 21, 3981 (1981) and (1986). references cited therein. A.W.M. Lee, V.S. Martin, M. Behrens, T. Katsuki, Sharpless, C.H. 6. K.B. 589 Takatani, S.M. Viti, F.J. Walker, S.S. Woodard, Pure App l.Chem., 55, Manta, J.D. Martin, Alvarez E. Let; a, 2093 (1988). M.L.iiguez, C. Ruiz-Phrez, Martin, 2097 (19881. Tetrahedron Lett., M. Kugamai, J. Soo Lee, T. Yasumoto, 8. (aj Mi .Murata, 5869 (1987). (b) Y.Y. Lin, M. Risk, S-M. Ray, D.V. Engen, J. Clardy, 28, J. Golik, J.C. James, K. Nakanishi, J.Am.Chem.Soc., 103, 6773 (1981). (c) H.N. Chou, H. Bando, G.V. Duyne, J. Clardy, J.Am.Chem.Soc., Y. Shimizu, 7.
3728
108, 514 (1986). 9. Unpublished results. orthorhombic, space group Fdd2, 10. Crystal data for 10: C12HltI202, 43.570 (341, b=32.7_61 (IL), c=8.584 (3) ii; V=12104 A3, Z=32. Data we:: AED computer-controlled Siemens four circle collected on a diffractometer, with GuKa graphite monochromated radiation. Of 2354 measured independent reflections. 2027 with Ia20 (I) were considered as The structure was solved by Patterson method (SHELXS-86) and observed. sucessive Fourier synthesis (XRAY-80): An empirical absorption correction was performed (DIFABS). Hvdroaen for carbon atoms olaced in calculated with anisotropic iodine atoms, Full matrix I..s”. refinement, positions. for isotropic carbon and oxygen atoms and fixed isotropic contribution hydrogens. Final R=0.077. 11. Crystal data for x: orthorhogbic, spacg group P 21/n, a= C12H,aI202, 8.428 (16), b=24.299 (76), c=l4.052 (60) A; V=2877 A3, Z=B. Of 3247 2665 with 1220(I) were considered as independent reflections, measured The structure was solved and refined as above. Final R=O.O76. observed. The details for both crystal structures will be given in a full paper. 12. 'H- and 'SC NMR spectra of selected compounds follow. 6: 'H NMR (CDC13) a5.82(1H, ddd, 5~10.5, 8.0, 8.0 Hz), 5.36(5H, m), 4.33TlH, m), 2.SS(lH, 7.4, 7.~3~z~idf."O~~~,o~~j J=:~95j(~j5 Hz); 13C NMR (CDC13) ddd, J=15.5, 128.0(d), 65.1(d), a135.1(d),3;3;iWjd), 29.6(i), 2&0(t)' 22.;(t). +:'H iMR (Cm131 s5.32(4H, 37*1(t), did, J=l4.0, 8.2, I.; Hz), 3.30TC3H, ddd, J=9.8, 4.5, 4.5 3.42(C& J=8.2 4.5 Hz)* 13C NMR (CDC13) 6131 7(d) 130 9(d) 128r9(~j~7i~t";cd~d~66.3(d~~ 61 l(d)' 58 O(d) 35 l(t) 3; l(tj 28*0(t)' '3.6;(CzH'br d J&O.: Hz)' 22.1(t). IO: 'H NhR (CDC13jS4.03(C1; br's) 3.79(C3H, ddd, J=lO.6, 7.5, 7.3 Hz) !?.06(C6Ha, ddd, Ji13.6' 7.5 7.4 Hzj 2.9l(C4Hb, ddd, J=13.6, 7.4, 7.3 Hzj, 4.27(CsH, ddd, J=I2.0: 7.4: 7.4 Hz) ;.;'A;;", ddd, J=l2.0, 12.0, 4.0 Hz), 2.34(C7Ha, dddd, J=I3.5, 12.0, 3.0, * 2.48(C7Hb, a) 2.97(CsHa m) 1.72(CaHb, m), 5.2O(CsH, ddd, J= 11.4, l;.O, 2.6 Hz), 5.iO(C,oH, dd:, JLIl.0,
'H NMR (CDCls! 64.O(C1H, m), 3.53(CzH, d, 5=2-O Hz), 4.48(CjH, ddd, J=4.0 2.4, 2.0 Hz), 3.55(CsH, ddd, J=9.6, 9.6, 1.3 Hz), 4.0(CsH, m), 5.4(CsH, '3C NMR (CDC13)a 74.O(Cl) 7O.O(C2) 31 9(C3) 38 5(C4) ~~:,~$'"3~'I~~b) 43 l(C7) 29 7(C8) 12; 8(C9) I;2 4.iCl0) '22 t(W) 27.4(Cl2j.x: 'H NkR (iDC1&3.;(C,H,'m), :.8(&i, m); 3.50tCsH; dd, JL 10.5, 1.7 Hz), 3.2(CaH, m), 3.78(CsH, ddd, J=l3.2, 10.3, 3.0 Hz). 2: 'H NMR (CDC13) 6 3.80(ClH, CzH, m), 4.58(CjH, ddd, J=9.9, 3.5, 3.5 Hz), g.Tz (CJHa, ddd, J=l5.1, 8.9, 3.5 Hz), 2.78(C4Hb, dd, J=15.1, 2.6 Hz), . (CsH, CsH, m), 5.56 (CaH, CloH, m). (Received in UK 11 May 1989)