Dihydroxylation of the triene subunit of rapamycin

Journal of Organic Chemistry

Volumn 63, Issue 26, 1998, Pages 10069-10073

  Sedrani, Richard ^a   Thai, Binh ^a   France, Julien ^a   Cottons, Sylvain ^a  

^a NOVARTIS PHARMA AG   (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

RAPAMYCIN;

ARTICLE; CARBON NUCLEAR MAGNETIC RESONANCE; CRYSTAL STRUCTURE; DRUG CONFORMATION; DRUG STRUCTURE; HYDROXYLATION; PROTON NUCLEAR MAGNETIC RESONANCE;

EID: 0032567480     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo9816820     Document Type: Article

References (32)

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24. The use of bissilylated rapamycin 2 was made necessary by the fact that unprotected rapamycin is insoluble in the biphasic fert-butyl alcohol:water mixture recommended for these reactions. Preclusion of the second cycle and of polyhydroxylation calls for such a biphasic solvent system. Attempts to use nonwater miscible organic .solvents capable of solubilizing rapamycin, such as méthylène chloride, toluene, or diethyl ether, led to no reaction.
25. For a standard procedure, see: Sharpless, K. B.; Amberg, W.; Bennani, Y. L.; Crispino, G. A.; Härtung, 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 5-fold higher than those recommended in the published standard procedure (see Experimental Section for more details).
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