Model studies directed toward microalga polyether macrolides: A route to 12-carbon tetrahydrofuran and tetrahydropyran subunits

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 D...

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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)