Synthesis of the functionalized tricyclic core of lactonamycin by oxidative dearomatization

Organic Letters

Volumn 2, Issue 22, 2000, Pages 3493-3496

  Cox, Christopher ^a   Danishefsky, Samuel J ^a,b  

^a Och Spine at New York Presbyterian Hospitals   (United States)

^b MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; INDOLE DERIVATIVE; LACTONAMYCIN; NAPHTHOQUINONE;

ARTICLE; CHEMISTRY; CONFORMATION; DRUG DESIGN; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

ANTI-BACTERIAL AGENTS; DRUG DESIGN; INDICATORS AND REAGENTS; INDOLES; MOLECULAR CONFORMATION; NAPHTHOQUINONES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0034597522     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol006531+     Document Type: Article

References (20)

1. (a) Isolation and biological evaluation: Matsumoto, Y.; Tsuchida, T.; Maruyama, M.; Kinoshita, N.; Homma, Y.; Iinuma, H.; Sawa, T.; Hamada, M.; Takeuchi, T.; Heida, N.; Yoshioka, T. J. Antibiot. 1999, 52, 269.
2. (b) Structure determination: Matsumoto, Y.; Tsuchida, T.; Nakamura, H.; Sawa, R.; Takahashi, Y.; Naganawa, H.; Inuma, H.; Sawa, T.; Takeuchi, T.; Shiro, M. J. Antibiot. 1999, 52, 276.
3. 4, see: (a) Wessely, F.; Sinwell, F. Montasch. Chem. 1950, 81, 1055.
4. This venerable reaction was advanced by the pioneering work of Yates to include intermolecular trapping by various carboxylic acids in inert solvents, see: (b) Yates, P.; Auksi, H. J. Chem. Soc., Chem. Commun. 1976, 1016.
5. (c) Yates, P. Auksi, H. Can. J. Chem. 1979, 57, 2853.
6. 4 are scarce in the chemical literature, the analogous use of hypervalent iodine reagents is well studied. For the use of I(III) reagents in synthesis, see: (a) Varvoglis, A. Tetrahedron 1997, 53, 1179.
7. (b) Kitamura, T.; Fujiwara, Y. Org. Prep. Proc. Int. 1997, 29, 409.
8. (c) Wirth, T.; Hirt, U. H. Synthesis 1999, 1271.
9. The esters 6 and 7 were extremely sensitive to both acid and base due to facile formation of the corresponding α,β-unsaturated ester, which also comes into conjugation with the aromatic ring. Acetal 7 was prepared with a number of other ester protecting groups, including allyl, benzyl, 2-(trimethylsilyl)ethyl, and tert-butyldiphenylsilyl. However, these too could not be removed without concurrent destruction of the acetal. Direct addition of the dianion of acetic acid also failed due to competing deprotonation of the highly acidic benzylic protons in 5.
10. We could obtain analytically pure 10 in 10-20% yield after quickly passing the crude material through Florisil, or in up to 50-60% of less pure material by an aqueous wash of the crude reaction mixture. Disappointingly, attempted epoxidation led predominately to decomposition, providing only a trace of material with NMR and LRMS signals consistent with those of the desired a-hydroxyketone.
11. Napolitano, E.; Spinelli, G.; Fiaschi, R.; Marsili, A. Synthesis 1985, 38.
12. Watanabe, M.; Morimoto, H.; Nogami, K.; Ijichi, S.; Furukawa, S. Chem. Pharm. Bull 1993, 41, 968.
13. While approach from the bottom face is significantly hindered by the lactone ring, epoxidation from the top face would provide the highly strained trans-fused 6:5 ring system. Additionally, π-overlap between the double bond and the proximal β-disposed ketone might have favored attack from the α-face: cf. Woodward, R. B.; Bader, F. E.; Bickel, H.; Frey, A. J.; Kierstead, R. W. Tetrahedron 1958, 2, 1.
14. Crystallographic data for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Center as supplementary publication numbers CCDC-149057 (20b) and CCDC-149058 (27).
15. For instance, epoxidation with trifluoroperacetic acid provided an approximately 1:1 ratio of 20a:20b; however, the yield was low, presumably due to competing processes such as protonation of the enol ether and/or Baeyer-Villiger oxidation.
16. As expected, density functional calculations (pBP/DN*) confirm that the desired 20a is favored thermodynamically with respect to 20b (3.1 kcal/mol). We thank Professor James Leighton for access to his SGI O2 running Spartan 5.1.2 to perform this analysis.
17. For an excellent review of substrate-directed reactions in organic synthesis, see: (a) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307. Some years ago we made use of the sequence of ring opening of a lactone, hydroxyl-directed epoxidation, and re-lactonization in the total synthesis of vernolepin, see: (b) Danishefsky, S.; Kitahara, T.; Schuda, P. F.; Etheredge, S. J. J. Am. Chem. Soc. 1976, 98, 3028.
18. For an excellent review of substrate-directed reactions in organic synthesis, see: (a) Hoveyda, A. H.; Evans, D. A.; Fu, G. C. Chem. Rev. 1993, 93, 1307. Some years ago we made use of the sequence of ring opening of a lactone, hydroxyl-directed epoxidation, and re-lactonization in the total synthesis of vernolepin, see: (b) Danishefsky, S.; Kitahara, T.; Schuda, P. F.; Etheredge, S. J. J. Am. Chem. Soc. 1976, 98, 3028.
19. The stereochemistry at the lactone α-carbon was not determined.
20. Elliott, R. P.; Fleet, G. W. J.; Gyoung, Y. S.; Ramsden, N. G.; Smith, C. Tetrahedron Lett. 1990, 3785.