Asymmetric synthesis of 5,5-disubstituted thiotetronic acids using an allyl xanthate to dithiocarbonate rearrangement: total synthesis of (5S)-thiolactomycin with revision of the absolute configuration of the natural

Abstract

An asymmetric synthesis of thiotetronic acids related to the antibiotics thiolactomycin 1 and thiotetromycin 2 has been developed in which the key step is a stereoselective [3.3]-rearrangement of an allyl xanthate to the corresponding dithiocarbonate. Thus, the xanthates (S)- and (R)-19 are rearranged efficiently to the dithiocarbonates (S)- and (R)-20. Hydrolysis of the dithiocarbonates with in situ S-alkylation gives the thioethers (S)- and (R)-22 which are converted into the acyl imidazolides (S)- and (R)-27. These are used to acylate methyl propanoate, methyl phenylacetate and ethyl acetate to give the keto esters 28–30 which are converted into the thiotetronic acids 31–33 by deprotection using trifluoroacetic acid–anisole. The 3-phenylthiotetronic acid 32 is completely enolic in both [²H]chloroform and [²H₆]dimethyl sulfoxide, but 15% of the keto tautomer 40 of the 3-methyl compound 31 is present in [²H]chloroform. The 3-unsubstituted thiotetronic acid 33 is 100% enolic in [²H₆]dimethyl sulfoxide and exists completely as the keto tautomer 41 in [²H]chloroform.Ozonolysis of the thioether (S)-22 gives the aldehyde 45 which is converted into the diene 42. Hydroboration–oxidation of this diene gives the alcohol 79 which is converted into the selenide 80. This is taken through to the thiotetronic acid 85, which via selective Se-methylation and base-induced elimination gives (5S)-thiolactomycin (S)-1. This is laevorotatory and hence is the enantiomer of the natural product which must therefore be the (5R)-enantiomer (R)-1.

References

1. H. Sasaki, H. Oishi, T. Hayashi, I. Matsuura, K. Ando and M. Sawada, J. Antibiotics, 1982, 35, 396; T. Noto, S. Miyakawa, H. Oishi, H. Endo and H. Okazaki, J. Antibiotics, 1982, 35, 401; S. Miyakawa, K. Suzuki, T. Noto, Y. Harada and H. Okazaki, J. Antibiotics, 1982, 35, 411; T. Hayashi, O. Yamamoto, H. Sasaki and H. Okazaki, J. Antibiotics, 1984, 37, 1456.
2. S. Omura, A. Nakagawa, R. Iwata and A. Hatano, J. Antibiotics, 1983, 36, 1781; S. Omura, Y. Iwai, A. Nakagawa, R. Iwata, Y. Takahashi, H. Shimizu and T. Tanaka, J. Antibiotics, 1983, 36, 109.
3. T. Sato, K. Suzuki, S. Kadota, K. Abe, S. Takamura and M. Iwanami, J. Antibiotics, 1989, 42, 890.
4. C. Rapp, G. Jung, C. Isselhorst-Scharr and H. Zahner, Annalen, 1988, 1043.
5. L. A. Dolak, T. M. Castle, S. E. Truesdell and O. K. Sebek, J. Antibiotics, 1986, 39, 26.
6. E. Benary, Berichte, 1913, 46, 2103.
7. J. Z. Mortensen, B. Hedegaard and S.-O. Lawesson, Tetrahedron, 1971, 27, 3839.
8. D. M. O'Mant, J. Chem. Soc. C, 1968, 1501.
9. K. Tsuzuki and S. Omura, J. Antibiotics, 1983, 36, 1589.
10. J. Brennan and P. J. Murphy, Tetrahedron Lett., 1988, 29, 2063.
11. C.-L. J. Wang and J. M. Salvino, Tetrahedron Lett., 1984, 25, 5243.
12. Preliminary communication: M. S. Chambers, E. J. Thomas and D. J. Williams, J. Chem. Soc., Chem. Commun., 1987, 1228.
13. Preliminary communication: M. S. Chambers and E. J. Thomas, J. Chem. Soc., Chem. Commun., 1989, 23.
14. T. Taguchi, Y. Kawazoe, K. Yoshihira, H. Kanayama, M. Mori, K. Tabata and K. Harano, Tetrahedron Lett., 1965, 2717; S. G. Smith, J. Am. Chem. Soc., 1961, 83, 4285; R. J. Ferrier and N. Vethaviyasar, J. Chem. Soc., Chem. Commun., 1970, 1385; K. Harano and T. Taguchi, Chem. Pharm. Bull., 1972, 20, 2357; T. Nakai and A. Ari-izumi, Tetrahedron Lett., 1976, 2335; Y. Ueno, H. Sano and M. Okawara, Tetrahedron Lett., 1980, 21, 1767.
15. M. Hirama, T. Shigemoto and S. Ito, J. Org. Chem., 1987, 52, 3342.
16. O. Mitsunobu, Synthesis, 1981, 1.
17. J. A. Dale, D. L. Dull and H. S. Mosher, J. Org. Chem., 1969, 34, 2543.
18. S. Akabori, S. Sakakibara, Y. Shimonishi and Y. Nobuhara, Bull. Chem. Soc. Jpn., 1964, 37, 433.
19. S. Trippett and D. M. Walker, J. Chem. Soc., 1961, 1266.
20. R. H. Schlessinger, M. A. Poss, S. Richardson and P. Lin, Tetrahedron Lett., 1985, 26, 2391.
21. O. Nishimura, C. Kitada and M. Fujino, Chem. Pharm. Bull., 1978, 26, 1576.
22. B. H. Lipshutz and J. J. Pegram, Tetrahedron Lett., 1980, 21, 3343.
23. E. J. Corey, J.-L. Gras and P. Ulrich, Tetrahedron Lett., 1976, 809.
24. D. J. Faulkner and M. R. Petersen, J. Am. Chem. Soc., 1973, 95, 553.
25. P. L. Stotter and K. A. Hill, Tetrahedron Lett., 1975, 1679.
26. R. A. Bell and M. B. Gravestock, Can. J. Chem., 1969, 47, 2099.
27. H. Bauer, Berichte, 1913, 46, 92; S. Uemura, A. Toshimitsu, M. Okano and K. Ichikawa, Bull. Chem. Soc. Jpn., 1975, 48, 1925.
28. P. A. Grieco, S. Gilman and M. Nishizawa, J. Org. Chem., 1976, 41, 1485.
29. R. Walter and J. Roy, J. Org. Chem., 1971, 36, 2561; K. B. Sharpless, M. W. Young and R. F. Lauer, Tetrahedron Lett., 1973, 1979; K. B. Sharpless and R. F. Lauer, J. Am. Chem. Soc., 1973, 95, 2697; C. A. Wilson, II and T. A. Bryson, J. Org. Chem., 1975, 40, 800.
30. H. J. Reich and F. Chow, J. Chem. Soc., Chem. Commun., 1975, 790; H. J. Reich and S. K. Shah, J. Am. Chem. Soc., 1975, 97, 3250; H. J. Reich and J. M. Renga, J. Org. Chem., 1975, 40, 3313.
31. P. G. Gassman, T. Miura and A. Mossman, J. Org. Chem., 1982, 47, 954.
32. S. Halazy and A. Krief, Tetrahedron Lett., 1979, 4233.