Absolute configuration of phorboxazoles A and B from the marine sponge Phorbas sp. 1. Macrolide and hemiketal rings

Journal of the American Chemical Society

Volumn 118, Issue 39, 1996, Pages 9422-9423

  Searle, Philip A ^a   Molinski, Tadeusz F ^a   Brzezinski, Linda Joy ^b   Leahy, James W ^b  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC AGENT; MACROLIDE; OXAZOLE DERIVATIVE; PHORBOXAZOLE A; PHORBOXAZOLE B; UNCLASSIFIED DRUG;

ARTICLE; CHIRALITY; DRUG STRUCTURE; NUCLEAR MAGNETIC RESONANCE;

EID: 0029854666     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja962092r     Document Type: Article

References (23)

1. Searle, P. A.; Molinski, T. F. J. Am. Chem. Soc. 1995, 117, 8126-8131.
2. -9 M). Compounds 1 and 2 had essentially the same activity profiles. We are grateful to Drs. Jill Johnson and Anthony B. Mauger, National Cancer Institute, for these data.The phorboxazoles A and B have been selected by the NCI for in vivo antitumor trials.
3. -9 M). Compounds 1 and 2 had essentially the same activity profiles. We are grateful to Drs. Jill Johnson and Anthony B. Mauger, National Cancer Institute, for these data.The phorboxazoles A and B have been selected by the NCI for in vivo antitumor trials.
4. -9 M). Compounds 1 and 2 had essentially the same activity profiles. We are grateful to Drs. Jill Johnson and Anthony B. Mauger, National Cancer Institute, for these data.The phorboxazoles A and B have been selected by the NCI for in vivo antitumor trials.
5. For the synthesis and properties of complex polyketide macrolides of marine and terrestrial origin see: (a) Norcross, R. D.; Paterson, I. Chem. Rev. 1995, 95, 2041-2114. (b) Omura, S. Macrolide Antibiotics: Chemistry, Biology and Practice; Academic Press: Orlando, FL, 1984; p 635.
6. For the synthesis and properties of complex polyketide macrolides of marine and terrestrial origin see: (a) Norcross, R. D.; Paterson, I. Chem. Rev. 1995, 95, 2041-2114. (b) Omura, S. Macrolide Antibiotics: Chemistry, Biology and Practice; Academic Press: Orlando, FL, 1984; p 635.
7. Ohtani, I.; Kusumi, T.; Kashman, Y. Kakisawa, H. J. Am. Chem. Soc. 1991, 113, 4092-4096.
8. + m/z 1455.5095. See supporting information for 500 MHz 1H NMR, DQFCOSY, and 1H assignments.
9. Rance, M.; Sørensen, O. W., Bodenhausen, G.; Wagner, G.; Ernst, R. R.; Wüthrich, K. Biochem. Biophys. Res. Commun. 1983, 117, 479-485.
10. The H47 signal showed an anomalous Δδ (-27 ppb) due to placement of the vinylmethyl syn to the MTPA group and in the shielding region of the phenyl ring.
11. The correct macrolide ring configuration is, therefore, opposite to that depicted for 1 in ref 1.
12. 1H NMR without recourse to models is illustrated by the elucidation of palytoxin stereochemistry. See the following citations and references cited within: (a) Moore, R. E.; Bartolini, G.; Barchi, J. J. Am. Chem. Soc. 1982, 104, 3776-3779. (b) Klein, L. L.; McWhorter, W. W., Jr.; Ko, S. S.; Pfaff, K.-P.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7362-7364. (c) Ko, S. S.; Finan, J. M.; Yonaga, M.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7364-7367. (d) Fujioka, H.; Christ, W. J.; Cha, J. K.; Leder, J.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7367-7369. (e) Cha, J. K.; Christ, W. J.; Finan, J. M.; Fujioka, H.; Kishi, Y.; Klein, L. L.; Ko, S. S.; Leder, J.; McWhorter Jr, W. W.; Pfaff, K.-P.; Yonaga, M.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7369-7371.
13. 1H NMR without recourse to models is illustrated by the elucidation of palytoxin stereochemistry. See the following citations and references cited within: (a) Moore, R. E.; Bartolini, G.; Barchi, J. J. Am. Chem. Soc. 1982, 104, 3776-3779. (b) Klein, L. L.; McWhorter, W. W., Jr.; Ko, S. S.; Pfaff, K.-P.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7362-7364. (c) Ko, S. S.; Finan, J. M.; Yonaga, M.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7364-7367. (d) Fujioka, H.; Christ, W. J.; Cha, J. K.; Leder, J.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7367-7369. (e) Cha, J. K.; Christ, W. J.; Finan, J. M.; Fujioka, H.; Kishi, Y.; Klein, L. L.; Ko, S. S.; Leder, J.; McWhorter Jr, W. W.; Pfaff, K.-P.; Yonaga, M.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7369-7371.
14. 1H NMR without recourse to models is illustrated by the elucidation of palytoxin stereochemistry. See the following citations and references cited within: (a) Moore, R. E.; Bartolini, G.; Barchi, J. J. Am. Chem. Soc. 1982, 104, 3776-3779. (b) Klein, L. L.; McWhorter, W. W., Jr.; Ko, S. S.; Pfaff, K.-P.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7362-7364. (c) Ko, S. S.; Finan, J. M.; Yonaga, M.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7364-7367. (d) Fujioka, H.; Christ, W. J.; Cha, J. K.; Leder, J.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7367-7369. (e) Cha, J. K.; Christ, W. J.; Finan, J. M.; Fujioka, H.; Kishi, Y.; Klein, L. L.; Ko, S. S.; Leder, J.; McWhorter Jr, W. W.; Pfaff, K.-P.; Yonaga, M.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7369-7371.
15. 1H NMR without recourse to models is illustrated by the elucidation of palytoxin stereochemistry. See the following citations and references cited within: (a) Moore, R. E.; Bartolini, G.; Barchi, J. J. Am. Chem. Soc. 1982, 104, 3776-3779. (b) Klein, L. L.; McWhorter, W. W., Jr.; Ko, S. S.; Pfaff, K.-P.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7362-7364. (c) Ko, S. S.; Finan, J. M.; Yonaga, M.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7364-7367. (d) Fujioka, H.; Christ, W. J.; Cha, J. K.; Leder, J.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7367-7369. (e) Cha, J. K.; Christ, W. J.; Finan, J. M.; Fujioka, H.; Kishi, Y.; Klein, L. L.; Ko, S. S.; Leder, J.; McWhorter Jr, W. W.; Pfaff, K.-P.; Yonaga, M.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7369-7371.
16. 1H NMR without recourse to models is illustrated by the elucidation of palytoxin stereochemistry. See the following citations and references cited within: (a) Moore, R. E.; Bartolini, G.; Barchi, J. J. Am. Chem. Soc. 1982, 104, 3776-3779. (b) Klein, L. L.; McWhorter, W. W., Jr.; Ko, S. S.; Pfaff, K.-P.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7362-7364. (c) Ko, S. S.; Finan, J. M.; Yonaga, M.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7364-7367. (d) Fujioka, H.; Christ, W. J.; Cha, J. K.; Leder, J.; Kishi, Y.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7367-7369. (e) Cha, J. K.; Christ, W. J.; Finan, J. M.; Fujioka, H.; Kishi, Y.; Klein, L. L.; Ko, S. S.; Leder, J.; McWhorter Jr, W. W.; Pfaff, K.-P.; Yonaga, M.; Uemura, D.; Hirata, Y. J. Am. Chem. Soc. 1982, 104, 7369-7371.
17. Clive, D. L. J.; Murthy, K. S. K.; Wee, A. G. H.; Prasad, J. S.; da Silva, G. V. J.; Majewski, M.; Anderson, P. C.; Evans, C. F.; Haugen, R. D.; Heerze, L. D.; Barrie, J. R. J. Am. Chem. Soc. 1990, 112, 3018. The product S-aldehyde 6 was >99% ee.
18. 13C NMR spectra and elemental analyses.
19. Keck, G. E.; Tarbet, K. H.; Geraci, L. S. J. Am. Chem. Soc. 1993, 115, 8467.
20. Compound 9 was assigned an axial OMe group, as expected from the anomeric effect and by analogy with compound number 13 reported in the total synthesis of acutiphycin. Smith, A. B.; Chen, S. S. Y.; Nelson, F. C.; Reichert, J. M.; Salvatore, B. A. J. Am. Chem. Soc. 1995, 117, 12013-12014. The oxane hemiketal OH group in acutiphycin is also axial, as is C33 OH in 1. Barchi, J. J.; Moore, R. E.; Patterson, G. M. L. J. Am. Chem. Soc. 1984, 106, 8193-8197. Bicyclic ketal 10 should, in theory, be transformed into 9 under the reaction conditions but thus far has proved to be remarkably stable.
21. Compound 9 was assigned an axial OMe group, as expected from the anomeric effect and by analogy with compound number 13 reported in the total synthesis of acutiphycin. Smith, A. B.; Chen, S. S. Y.; Nelson, F. C.; Reichert, J. M.; Salvatore, B. A. J. Am. Chem. Soc. 1995, 117, 12013-12014. The oxane hemiketal OH group in acutiphycin is also axial, as is C33 OH in 1. Barchi, J. J.; Moore, R. E.; Patterson, G. M. L. J. Am. Chem. Soc. 1984, 106, 8193-8197. Bicyclic ketal 10 should, in theory, be transformed into 9 under the reaction conditions but thus far has proved to be remarkably stable.
22. Van Horn, D. E.; Negishi, E. J. Am. Chem. Soc. 1978, 100, 2252.
23. 1H NMR signal, although this time positive (Δδ + 20 ppb) because of its antipodal relationship to 1 (see footnote 7). We were surprised to find that the major product of this addition, 5a, was the isomer expected from non-chelation-controlled addition. Efforts are underway to improve stereocontrol in the generation of this center. Nevertheless, both diastereomers of 5 were made available for comparison with 1.