Toward a total synthesis of the immunosuppressant sanglifehrin A. Preparation of two relay compounds by degradation and their use in the reassembly of the natural product

Journal of Organic Chemistry

Volumn 64, Issue 26, 1999, Pages 9632-9639

  Metternich, Rainer ^a   Denni, Donatienne ^a   Thai, Binh ^a   Sedrani, Richard ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLOSPORIN A; IMMUNOSUPPRESSIVE AGENT; NATURAL PRODUCT; RAPAMYCIN; SANGLIFEHRIN A; TACROLIMUS;

ARTICLE; CHEMICAL REACTION; DRUG ACTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; MOLECULAR INTERACTION; REACTION ANALYSIS;

EID: 0033601270     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9912395     Document Type: Article

References (52)

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11. Examples of macrocyclic natural products containing piperazic acid: (Antibiotic GE3) (a) Sakai, Y.; Yoshida, T.; Tsujita, T.; Ochiai, K.; Agatsuma, T.; Saitoh, Y.; Tanaka, F.; Akiyama, T.; Akinaga, S.; Mizukami, T. J. Antibiot. 1997, 50, 659-664. (b) Agatsuma, T.; Sakai, Y.; Mizukami, T.; Saitoh, Y. J. Antibiot. 1997, 50, 704-708. (Aurantimycins) (c) Graefe, U.; Schlegel, R.; Ritzau, M.; Ihn, W.; Dornberger, K.; Stengel, C.; Fleck, W. F.; Gutsche, W.; Haertl, A.; Paulus, E. F. J. Antibiot. 1995, 48, 119-125. (Verucopeptin) (d) Nishiyama, Y.; Sugawara, K.; Tomita, K.; Yamamoto, H.; Kamei, H.; Oki, T. J. Antibiot. 1993, 46, 921-927. (e) Sugawara, K.; Toda, S.; Moriyama, T.; Konishi, M.; Oki, T. J. Antibiot. 1993, 46, 928-935. (Antibiotic A83586C) (f) Smitka, T. A.; Deeter, J. B.; Hunt, A. H.; Mertz, F. P.; Ellis, R. M.; Boeck, L. D.; Yao, R. C. J. Antibiot. 1988, 41, 726-733. (Azinothricin) (g) Maehr, H.; Liu, C. M.; Palleroni, N. J.; Smallheer, J.; Todaro, L.; Williams, T. H.; Blount, J. F. J. Antibiot. 1986, 39, 17-25.
12. Examples of macrocyclic natural products containing piperazic acid: (Antibiotic GE3) (a) Sakai, Y.; Yoshida, T.; Tsujita, T.; Ochiai, K.; Agatsuma, T.; Saitoh, Y.; Tanaka, F.; Akiyama, T.; Akinaga, S.; Mizukami, T. J. Antibiot. 1997, 50, 659-664. (b) Agatsuma, T.; Sakai, Y.; Mizukami, T.; Saitoh, Y. J. Antibiot. 1997, 50, 704-708. (Aurantimycins) (c) Graefe, U.; Schlegel, R.; Ritzau, M.; Ihn, W.; Dornberger, K.; Stengel, C.; Fleck, W. F.; Gutsche, W.; Haertl, A.; Paulus, E. F. J. Antibiot. 1995, 48, 119-125. (Verucopeptin) (d) Nishiyama, Y.; Sugawara, K.; Tomita, K.; Yamamoto, H.; Kamei, H.; Oki, T. J. Antibiot. 1993, 46, 921-927. (e) Sugawara, K.; Toda, S.; Moriyama, T.; Konishi, M.; Oki, T. J. Antibiot. 1993, 46, 928-935. (Antibiotic A83586C) (f) Smitka, T. A.; Deeter, J. B.; Hunt, A. H.; Mertz, F. P.; Ellis, R. M.; Boeck, L. D.; Yao, R. C. J. Antibiot. 1988, 41, 726-733. (Azinothricin) (g) Maehr, H.; Liu, C. M.; Palleroni, N. J.; Smallheer, J.; Todaro, L.; Williams, T. H.; Blount, J. F. J. Antibiot. 1986, 39, 17-25.
13. Examples of macrocyclic natural products containing piperazic acid: (Antibiotic GE3) (a) Sakai, Y.; Yoshida, T.; Tsujita, T.; Ochiai, K.; Agatsuma, T.; Saitoh, Y.; Tanaka, F.; Akiyama, T.; Akinaga, S.; Mizukami, T. J. Antibiot. 1997, 50, 659-664. (b) Agatsuma, T.; Sakai, Y.; Mizukami, T.; Saitoh, Y. J. Antibiot. 1997, 50, 704-708. (Aurantimycins) (c) Graefe, U.; Schlegel, R.; Ritzau, M.; Ihn, W.; Dornberger, K.; Stengel, C.; Fleck, W. F.; Gutsche, W.; Haertl, A.; Paulus, E. F. J. Antibiot. 1995, 48, 119-125. (Verucopeptin) (d) Nishiyama, Y.; Sugawara, K.; Tomita, K.; Yamamoto, H.; Kamei, H.; Oki, T. J. Antibiot. 1993, 46, 921-927. (e) Sugawara, K.; Toda, S.; Moriyama, T.; Konishi, M.; Oki, T. J. Antibiot. 1993, 46, 928-935. (Antibiotic A83586C) (f) Smitka, T. A.; Deeter, J. B.; Hunt, A. H.; Mertz, F. P.; Ellis, R. M.; Boeck, L. D.; Yao, R. C. J. Antibiot. 1988, 41, 726-733. (Azinothricin) (g) Maehr, H.; Liu, C. M.; Palleroni, N. J.; Smallheer, J.; Todaro, L.; Williams, T. H.; Blount, J. F. J. Antibiot. 1986, 39, 17-25.
14. Examples of macrocyclic natural products containing piperazic acid: (Antibiotic GE3) (a) Sakai, Y.; Yoshida, T.; Tsujita, T.; Ochiai, K.; Agatsuma, T.; Saitoh, Y.; Tanaka, F.; Akiyama, T.; Akinaga, S.; Mizukami, T. J. Antibiot. 1997, 50, 659-664. (b) Agatsuma, T.; Sakai, Y.; Mizukami, T.; Saitoh, Y. J. Antibiot. 1997, 50, 704-708. (Aurantimycins) (c) Graefe, U.; Schlegel, R.; Ritzau, M.; Ihn, W.; Dornberger, K.; Stengel, C.; Fleck, W. F.; Gutsche, W.; Haertl, A.; Paulus, E. F. J. Antibiot. 1995, 48, 119-125. (Verucopeptin) (d) Nishiyama, Y.; Sugawara, K.; Tomita, K.; Yamamoto, H.; Kamei, H.; Oki, T. J. Antibiot. 1993, 46, 921-927. (e) Sugawara, K.; Toda, S.; Moriyama, T.; Konishi, M.; Oki, T. J. Antibiot. 1993, 46, 928-935. (Antibiotic A83586C) (f) Smitka, T. A.; Deeter, J. B.; Hunt, A. H.; Mertz, F. P.; Ellis, R. M.; Boeck, L. D.; Yao, R. C. J. Antibiot. 1988, 41, 726-733. (Azinothricin) (g) Maehr, H.; Liu, C. M.; Palleroni, N. J.; Smallheer, J.; Todaro, L.; Williams, T. H.; Blount, J. F. J. Antibiot. 1986, 39, 17-25.
15. Examples of macrocyclic natural products containing piperazic acid: (Antibiotic GE3) (a) Sakai, Y.; Yoshida, T.; Tsujita, T.; Ochiai, K.; Agatsuma, T.; Saitoh, Y.; Tanaka, F.; Akiyama, T.; Akinaga, S.; Mizukami, T. J. Antibiot. 1997, 50, 659-664. (b) Agatsuma, T.; Sakai, Y.; Mizukami, T.; Saitoh, Y. J. Antibiot. 1997, 50, 704-708. (Aurantimycins) (c) Graefe, U.; Schlegel, R.; Ritzau, M.; Ihn, W.; Dornberger, K.; Stengel, C.; Fleck, W. F.; Gutsche, W.; Haertl, A.; Paulus, E. F. J. Antibiot. 1995, 48, 119-125. (Verucopeptin) (d) Nishiyama, Y.; Sugawara, K.; Tomita, K.; Yamamoto, H.; Kamei, H.; Oki, T. J. Antibiot. 1993, 46, 921-927. (e) Sugawara, K.; Toda, S.; Moriyama, T.; Konishi, M.; Oki, T. J. Antibiot. 1993, 46, 928-935. (Antibiotic A83586C) (f) Smitka, T. A.; Deeter, J. B.; Hunt, A. H.; Mertz, F. P.; Ellis, R. M.; Boeck, L. D.; Yao, R. C. J. Antibiot. 1988, 41, 726-733. (Azinothricin) (g) Maehr, H.; Liu, C. M.; Palleroni, N. J.; Smallheer, J.; Todaro, L.; Williams, T. H.; Blount, J. F. J. Antibiot. 1986, 39, 17-25.
16. Examples of macrocyclic natural products containing piperazic acid: (Antibiotic GE3) (a) Sakai, Y.; Yoshida, T.; Tsujita, T.; Ochiai, K.; Agatsuma, T.; Saitoh, Y.; Tanaka, F.; Akiyama, T.; Akinaga, S.; Mizukami, T. J. Antibiot. 1997, 50, 659-664. (b) Agatsuma, T.; Sakai, Y.; Mizukami, T.; Saitoh, Y. J. Antibiot. 1997, 50, 704-708. (Aurantimycins) (c) Graefe, U.; Schlegel, R.; Ritzau, M.; Ihn, W.; Dornberger, K.; Stengel, C.; Fleck, W. F.; Gutsche, W.; Haertl, A.; Paulus, E. F. J. Antibiot. 1995, 48, 119-125. (Verucopeptin) (d) Nishiyama, Y.; Sugawara, K.; Tomita, K.; Yamamoto, H.; Kamei, H.; Oki, T. J. Antibiot. 1993, 46, 921-927. (e) Sugawara, K.; Toda, S.; Moriyama, T.; Konishi, M.; Oki, T. J. Antibiot. 1993, 46, 928-935. (Antibiotic A83586C) (f) Smitka, T. A.; Deeter, J. B.; Hunt, A. H.; Mertz, F. P.; Ellis, R. M.; Boeck, L. D.; Yao, R. C. J. Antibiot. 1988, 41, 726-733. (Azinothricin) (g) Maehr, H.; Liu, C. M.; Palleroni, N. J.; Smallheer, J.; Todaro, L.; Williams, T. H.; Blount, J. F. J. Antibiot. 1986, 39, 17-25.
17. For a report describing the synthesis of the tripeptide segment of sanglifehrin A, see: Bänteli, R.; Brun, I.; Hall, P.; Metternich, R. Tetrahedron Lett. 1999, 40, 2109-2112.
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19. For a synthesis of the sanglifehrin A macrocycle and a total synthesis of the natural product, see: (a) Nicolaou, K. C.; Ohshima, T.; Murphy, F.; Barluenga, S.; Xu, J.; Winssinger, N. Chem. Commun. 1999, 809-810. (b) Nicolaou, K. C.; Xu, J.; Murphy, F.; Barluenga, S.; Baudoin, O.; Wei, H.; Gray, D.; Ohshima, T. Angew. Chem., Int. Ed. Engl. 1999, 38, 2447-2451.
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27. For a standard procedure, see: Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Hartung, J.; Jeong, K.-S.; Kwong, H.-L.; Morikawa, K.; Wang, Z.-M.; Xu, D.; Zhang, X.-L. J. Org. Chem. 1992, 57, 2768-2771. In this study we added the individual components separately instead of using the premixed powder. Instead of potassium osmate, osmium tetraoxide solution was used. More importantly, the loads of osmium catalyst and phthalazine ligand were 15-and 6-fold higher, respectively, than those recommended in the published standard procedure (see the Experimental Section for more details).
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47. Recently a case has been described in which the use of 1-phenyl-1H-tetrazol-5-yl sulfones resulted in low E selectivity or even in preferential formation of the Z alkene: Williams, D. R.; Clark, M. P. Tetrahedron Lett. 1999, 40, 2291-2294.
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49. The acidic hydrolysis of the intramolecular ketal subunit of 16 to afford 1 stops at approximately 40-50% conversion. The yield given is for pure sanglifehrin A after HPLC purification. Despite extensive efforts, we were not able to improve this deprotection step. The addition of boric acid slightly increases conversions with respect to reactions performed in its absence. Furthermore, it allows side reactions which readily occur in aqueous acidic conditions and which are going to be reported elsewhere to be prevented. The beneficial effect of boric acid is presumably due to in situ trapping of the 1,3-diol function of 1 as the corresponding borate.
50. Brown, C. A. Synthesis 1974, 427-428.
51. 13C spectra of these compounds. The third isomer is presumably an amide bond rotamer. Only the signals corresponding to the major isomer are listed.
52. 6. Only the signals corresponding to the major isomer are listed.