The 14C radiolabelled synthesis of the cholesterol absorption inhibitor CP-148,623. A novel method for the incorporation of a 14C label in enones

Tetrahedron

Volumn 53, Issue 32, 1997, Pages 11007-11020

  DeNinno, Michael P ^a   McCarthy, Keith E ^a  

^a PFIZER INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTILIPEMIC AGENT; CARBON 14; CP 148623; PAMAQUESIDE; UNCLASSIFIED DRUG;

ARTICLE; DRUG PURIFICATION; DRUG SYNTHESIS; IN VITRO STUDY; ISOTOPE LABELING; MASS SPECTROMETRY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; REACTION ANALYSIS; TECHNIQUE;

EID: 0030742441     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(97)00361-X     Document Type: Article

References (18)

1. McCarthy, P.A.; DeNinno, M.P.; Morehouse, L.A.; Chandler, C.E.; Bangerter, F.W.; Wilson, T.C.; Urban, F.J.; Walinsky, S.W.; Cosgrove, P.O.; Duplantier, K.C.; Etienne, J.B.; Fowler, M.A.; Lambert, J.F.; O'Donnell, J.P.; Pezzullo, S.L.; Watson Jr., H.A.; Wilkins, R.W.; Zaccaro, L.M.; Zawistoski, M.P. J. Med. Chem. 1996, 39, 1935-1937.
2. Turner, R. B.; J. Am. Chem. Soc., 1950, 72, 579-585. Fujimoto, G. I.; Prager, J., J. Am. Chem. Soc., 1953, 75, 3259-3261. Belleau, B. J. Am. Chem. Soc. 1951, 73, 5441-5443. Henrick, C. A.; Bohme, E.; Edwards, J. A.; Fried, J. H., J. Am. Chem Soc., 1968, 90, 5926-5927. Rao, P. N.; Axelrod, L. R., J. Chem Soc., 1965, 1356-1359.
3. Turner, R. B.; J. Am. Chem. Soc., 1950, 72, 579-585. Fujimoto, G. I.; Prager, J., J. Am. Chem. Soc., 1953, 75, 3259-3261. Belleau, B. J. Am. Chem. Soc. 1951, 73, 5441-5443. Henrick, C. A.; Bohme, E.; Edwards, J. A.; Fried, J. H., J. Am. Chem Soc., 1968, 90, 5926-5927. Rao, P. N.; Axelrod, L. R., J. Chem Soc., 1965, 1356-1359.
4. Turner, R. B.; J. Am. Chem. Soc., 1950, 72, 579-585. Fujimoto, G. I.; Prager, J., J. Am. Chem. Soc., 1953, 75, 3259-3261. Belleau, B. J. Am. Chem. Soc. 1951, 73, 5441-5443. Henrick, C. A.; Bohme, E.; Edwards, J. A.; Fried, J. H., J. Am. Chem Soc., 1968, 90, 5926-5927. Rao, P. N.; Axelrod, L. R., J. Chem Soc., 1965, 1356-1359.
5. Turner, R. B.; J. Am. Chem. Soc., 1950, 72, 579-585. Fujimoto, G. I.; Prager, J., J. Am. Chem. Soc., 1953, 75, 3259-3261. Belleau, B. J. Am. Chem. Soc. 1951, 73, 5441-5443. Henrick, C. A.; Bohme, E.; Edwards, J. A.; Fried, J. H., J. Am. Chem Soc., 1968, 90, 5926-5927. Rao, P. N.; Axelrod, L. R., J. Chem Soc., 1965, 1356-1359.
6. Turner, R. B.; J. Am. Chem. Soc., 1950, 72, 579-585. Fujimoto, G. I.; Prager, J., J. Am. Chem. Soc., 1953, 75, 3259-3261. Belleau, B. J. Am. Chem. Soc. 1951, 73, 5441-5443. Henrick, C. A.; Bohme, E.; Edwards, J. A.; Fried, J. H., J. Am. Chem Soc., 1968, 90, 5926-5927. Rao, P. N.; Axelrod, L. R., J. Chem Soc., 1965, 1356-1359.
7. Engal, Ch. R.; Chowdhury, M.N.; Tetrahedron Lett. 1968, 17, 2107-2111. Kutney, J.P.; Vlattas, I.; Rao, G.V. Can. J. Chem., 1963, 41, 958-965.
8. Engal, Ch. R.; Chowdhury, M.N.; Tetrahedron Lett. 1968, 17, 2107-2111. Kutney, J.P.; Vlattas, I.; Rao, G.V. Can. J. Chem., 1963, 41, 958-965.
9. The large scale preps of CP-148,623 were used for toxicology and clinical studies. 11-Ketotigogenin is also available from Steraloids Inc., Wilton, N.H.
10. Baran, J.S.; Langford, D.D.; Laos, I.; Liang, C.D. Tetrahedron 1977, 33, 609-616.
11. Bailey, P.S., "Ozonation in Organic Chemistry", Academic: New York, 1978; Vol. 1. Bailey, P.S. Chem. Rev. 1958, 58, 925-1010. Everest, D.J.; Grant, P.K.; Slim, G.C.; Yeo, I.K.L. Aust. J. Chem. 1988, 41, 1025-1035. Cargill, R.L.; Wright, B.W. J. Org. Chem. 1975, 40, 120-122. Wadt, W.R.; Goddard III, W.A. J. Am. Chem. Soc. 1975, 97, 3004-3021.
12. Bailey, P.S., "Ozonation in Organic Chemistry", Academic: New York, 1978; Vol. 1. Bailey, P.S. Chem. Rev. 1958, 58, 925-1010. Everest, D.J.; Grant, P.K.; Slim, G.C.; Yeo, I.K.L. Aust. J. Chem. 1988, 41, 1025-1035. Cargill, R.L.; Wright, B.W. J. Org. Chem. 1975, 40, 120-122. Wadt, W.R.; Goddard III, W.A. J. Am. Chem. Soc. 1975, 97, 3004-3021.
13. Bailey, P.S., "Ozonation in Organic Chemistry", Academic: New York, 1978; Vol. 1. Bailey, P.S. Chem. Rev. 1958, 58, 925-1010. Everest, D.J.; Grant, P.K.; Slim, G.C.; Yeo, I.K.L. Aust. J. Chem. 1988, 41, 1025-1035. Cargill, R.L.; Wright, B.W. J. Org. Chem. 1975, 40, 120-122. Wadt, W.R.; Goddard III, W.A. J. Am. Chem. Soc. 1975, 97, 3004-3021.
14. Bailey, P.S., "Ozonation in Organic Chemistry", Academic: New York, 1978; Vol. 1. Bailey, P.S. Chem. Rev. 1958, 58, 925-1010. Everest, D.J.; Grant, P.K.; Slim, G.C.; Yeo, I.K.L. Aust. J. Chem. 1988, 41, 1025-1035. Cargill, R.L.; Wright, B.W. J. Org. Chem. 1975, 40, 120-122. Wadt, W.R.; Goddard III, W.A. J. Am. Chem. Soc. 1975, 97, 3004-3021.
15. Bailey, P.S., "Ozonation in Organic Chemistry", Academic: New York, 1978; Vol. 1. Bailey, P.S. Chem. Rev. 1958, 58, 925-1010. Everest, D.J.; Grant, P.K.; Slim, G.C.; Yeo, I.K.L. Aust. J. Chem. 1988, 41, 1025-1035. Cargill, R.L.; Wright, B.W. J. Org. Chem. 1975, 40, 120-122. Wadt, W.R.; Goddard III, W.A. J. Am. Chem. Soc. 1975, 97, 3004-3021.
16. DeNinno, M.P. J. Am. Chem. Soc. 1995, 117, 9927-9928.
17. We would like to thank Dr. David Leuck of Chemsyn Science Laboratories for carrying out this transformation.
18. Extended reaction times leads to decomposition of the enone. The reaction was monitored by radio-TLC until the maximum amount of enone 6 was formed, then the reaction was worked-up.