Tetrahedron Letters,Vol.25,No.21,pp 2209-2212,1984 0040-4039/84 $3.00 + .OO Printed in Great Britain 81984 Pergamon Press Ltd.

(+bCOLLETODIOL

SYNTHESIS FROM (S,S)-TARTARIC ACID AND (R)-~-HYDR~~Y-B~TYRI~ ACID

Peter Schnurrenberger, Ernst Hungerbühler, and Dieter Seebach*

Laboratorium für Organische Chemie der Eidgenössischen Technischen Hochschule, ETH-Zentrum, Universitätstrasse 16, CH-8092 Zürich (Switzerland)

Summahy: E- (RI -5-tfydkoxy-Z-hexenoic acid (4) and the acetovúde 06 E- (4R, 5R, 7R) -tihydtoxy-2- -ootenoic acid (31 am joined tu &e, a&tm depkotecLLon, (+J-coUeeeRo&oL (ll. The. nqnthue,s 06 thc two hq&oxq-ati& @am poey- (RI -3-hydhoxy-bt&anoa& (P/+BJ uñd (-)-Ramtah¿c acid, ~enpec.a%wLq, am otimd.

Of the unsymmetrical'), antibiotic 14-membered macrodiolides colletodiol (')2), graha-

mimycin3), and their congeners, only (-)-grahamimycin Al has been synthesized 4) so far. Seve-

ral attempts towards the synthesis of colletodiol failed 536) . In our own, numerous ap-

proaches5), this failure was mainly due to the pronounced tendency, under esterification con-

ditions, for HOR-elimination from the 4.5-position of the hexenoic acid moiety of colletodiol.

_l_: R = H (colletodiol) 3 4 -

2: R-R = C(CH3)2

In an act of desperation, we have now subjected a 1:l mixture of the two carboxylic

7) acids 3 and 4 to esterifying macrocyclization conditions . - - We isolated without difficulty,

albeit in only a few percent yield, the known 2) acetonide 2 of colletodiol. Deprotection 8)

furnished colletodiol l_, identical in every respect with an authentic sample, Details are

given in the accompanying table which also lists conditions, yields, and some other character-

2209

2210

istic data for the syntheses of 3 and 4, many intermediates of which should be useful enan-

tiomerically pure building blocks, also for other target structures gal .

5: X = OH, R = H -

6: X = OH, R = CH2C6H5(ZBn)

7: X = Br, R = Bn

8: X = S(CH2)3S 9:x=0 -

10 - 12: X = H/OBn -

13: X = H/OH -

14: x = 0 -

E-15: X = CH-COOCH3

16: R = CH(CH3)0C2H5(EE), -

X = H/OH

17: R = EE, X = 0 -

E-18: R = EE, X = CHCOOCH3

E_19: R = H, X = CHCOOCH3

The synthesis of the trihydroxy-acid derivative 3 starts from the now commercially avail- -

able dio1 5 Ifrom (-)-tartaric acid 9a) 1. Monobenzylation to 6 abolishes the C2-symmetry of -

the molecule'), substitution of the remaining OH-group by a bromine (el) and hence by a

2-methyl-1.3-dithian-2-yl group (+g), with subsequent Hg(II)-assisted thioacetal hydrolysis

produces the ketone 9. Non-stereoselective borohydride reduction,

by flash chromatography, and acetylation of 10 with inversion and -

figuration") concludes the overa11 diastereoselective conversion

(+_), Swehn oxidation (eo), WLM@-Hoknti olefination (+_),

separation of the epimers

of ll with retention of COI+ -

9 + 12. Oebenzylation --

and hydrolysis of both

ester groups furnishes the hydroxyacid 3 in ca. - 23 % yield for the ten steps from the dio1 2.

The methyl ester 19 of the C6-hydroxy-acid 4 was obtained following procedures described - -

for the preparation of the racemic material ") and of the analogous t-butyl-ester with (S)-

2212

Referentes and Footnotes

1)

2)

3)

4)

5)

6)

7)

8)

9)

10)

ll)

12)

13)

14)

There is also a group of C2-symmetrical, ló-membered natural macrodiolides, such as

pyrenophorin, vermiculin, conglobatin, and elaiophylin. For leading referentes see the

most recent paper describing our own synthetic efforts in this area: M.A. Stieh and

D. Seebach, Liebigs Ann. Chem. 1983, 939.

Constitution and absolute configuration: J.W. PoweAY and W.B. WhuiYey, J. Chem. Soc. (c)

1969, 911. - M.W. Lunnou and J. MucM.XCan, J. Chem. Soc., Perkin Trans., 1 1976, 184,

and earlier papers of MacU¿eeun's group cited therein. - Relative configuration:

R. Art&uXz, E. Hungenbühleh, and 2). Seebach, Helv. Chim. Acta 64, 1796 (1981).

R.C. Ronded et al., Tetrahedron Lett. I9til, 681; Antimicrobial Agents and Chemotherapy

1981, 153; US patent No. 4,220,718 (1980), Chem. Abstr. 94: 28879 h (1981).

a: W. Seidel and U. Seebach, Tetrahedron Lett. 1962, 159. - b: U. Gtingc&X, ibid.

1983, 287.

P. Schntienbtigti, projected Ph.D. thesis, ETH Zürich, 1984. Ful1 paper for publication

in Liebigs Ann. Chem., in preparation. - E. Hungehbükeeh, Dissertation No. 6862, ETH

Zürich, 1981.

0. tiunobu, M. Ebina, and T. Ogihcum, Chem. Lett. 1962, 373. - Lecture held by

0. Mtiunobu, June 13, 1983, Hoffmann La-Roche, Basel.

J. Inunuga, K. Hi~ata, H. Suefzi, T. Kc&uk¿, and M. Yumaguti, Bull. Chem. Soc. Japan

52, 1989 (1979).

Y. &Lndan, H.E. Motion, and Ch. Yoakim, Tetrahedron Lett. 24, 3969 (1983).

a: Cf. also the review article: U. Seebach and E. Hungehbükeetr, Modern Synthetic Methods

1980, Editor: R. Scheaaobd, Sauerländer, Aarau. - b: Mono-benzoylation: N. Cohm, 8.L.

Bunneh, R.J. LopkenLi_, F. Wang, M. Rohenbmgek, Y.-Y. L& E. Thom, and A.A. Liebmunn,

J. Am. Chem. Soc. 105, 3661 (1983).

Isomer ll was shown to have the correct configuration by deprotection to 1.3-dideoxy- -

-D-lyxo-hexitol, [aID = t11.5’; cf. J. Ngmmec, 2. Kc~tiov~, K. Kedti, and J. Jtij,

Collect, Czech. Chem. Commun. 33, 2097 (1968).

E. Hunge_&büketi, U. Seebuch, and U. Wawath, Helv. Chim. Acta 64, 1467 (1981).

U. Seebuch and M.F. ZUgti, Helv. Chim. Acta 65, 495 (1982). - P. Schnwcrrenbageh, M.F.

Zügeti, and U. Setbach, Helv. Chim. Acta 65, 1197 (1982). - Both, PHB and the monomeric

ester are now commercially available.

M. Qowtie, J.8. Ho.Pmti, and J.B. Lee, Chem. Ind. London 1966, 900.

0. M.L&unobu and M. Egucti, Bull. Chem. Soc. Jap. 44, 3427 (1971).

(Received in Germany 21 February 1984)