New synthetic strategies to vitamin D analogues modified at the side chain and D ring. Synthesis of 1α,25-dihydroxy-16-ene-vitamin D3 and C-20 analogues

Journal of Organic Chemistry

Volumn 64, Issue 9, 1999, Pages 3196-3206

  De Los Angeles Rey, María ^a   Martínez Pérez, José Antonio ^a   Fernández Gacio, Ana ^a   Halkes, Koen ^a   Fall, Yagamare ^a   Granja, Juan ^a   Mouriño, Antonio ^a  

^a UNIVERSITY OF SANTIAGO DE COMPOSTELA   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

1ALPHA,25 DIHYDROXY 16 ENE VITAMIN D3; CALCITRIOL; UNCLASSIFIED DRUG; VITAMIN D DERIVATIVE;

ALKYLATION; ARTICLE; CHEMICAL STRUCTURE; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION; SYNTHESIS;

EID: 0344573888     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo982393e     Document Type: Article

References (60)

1. This work was taken in part from the doctoral theses of María de los Angeles Rey and José Antonio Martínez (University of Santiago de Compostela) and was partially presented at the XVII Conference on Isoprenoids (Kracow, Poland, 1997).
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16. 2′ anti-displacement of allylic pivaloates, see: Schmuff, N. R.; Trost, B. M. J. Org. Chem. 1983, 48, 1404. (g) For construction of steroidal side chains with natural and nonnatural configurations at C20 using palladium-catalyzed allylic alkylation, see: (h) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1976, 98, 630. (i) Trost, B. M.; Matsumura, Y. J. Org. Chem. 1977, 42, 2036. (j) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1978, 100, 3435.
17. 2′ anti-displacement of allylic pivaloates, see: Schmuff, N. R.; Trost, B. M. J. Org. Chem. 1983, 48, 1404. (g) For construction of steroidal side chains with natural and nonnatural configurations at C20 using palladium-catalyzed allylic alkylation, see: (h) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1976, 98, 630. (i) Trost, B. M.; Matsumura, Y. J. Org. Chem. 1977, 42, 2036. (j) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1978, 100, 3435.
18. 2′ anti-displacement of allylic pivaloates, see: Schmuff, N. R.; Trost, B. M. J. Org. Chem. 1983, 48, 1404. (g) For construction of steroidal side chains with natural and nonnatural configurations at C20 using palladium-catalyzed allylic alkylation, see: (h) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1976, 98, 630. (i) Trost, B. M.; Matsumura, Y. J. Org. Chem. 1977, 42, 2036. (j) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1978, 100, 3435.
19. 2′ anti-displacement of allylic pivaloates, see: Schmuff, N. R.; Trost, B. M. J. Org. Chem. 1983, 48, 1404. (g) For construction of steroidal side chains with natural and nonnatural configurations at C20 using palladium-catalyzed allylic alkylation, see: (h) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1976, 98, 630. (i) Trost, B. M.; Matsumura, Y. J. Org. Chem. 1977, 42, 2036. (j) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1978, 100, 3435.
20. 2′ anti-displacement of allylic pivaloates, see: Schmuff, N. R.; Trost, B. M. J. Org. Chem. 1983, 48, 1404. (g) For construction of steroidal side chains with natural and nonnatural configurations at C20 using palladium-catalyzed allylic alkylation, see: (h) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1976, 98, 630. (i) Trost, B. M.; Matsumura, Y. J. Org. Chem. 1977, 42, 2036. (j) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1978, 100, 3435.
21. 2′ anti-displacement of allylic pivaloates, see: Schmuff, N. R.; Trost, B. M. J. Org. Chem. 1983, 48, 1404. (g) For construction of steroidal side chains with natural and nonnatural configurations at C20 using palladium-catalyzed allylic alkylation, see: (h) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1976, 98, 630. (i) Trost, B. M.; Matsumura, Y. J. Org. Chem. 1977, 42, 2036. (j) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1978, 100, 3435.
22. 2′ anti-displacement of allylic pivaloates, see: Schmuff, N. R.; Trost, B. M. J. Org. Chem. 1983, 48, 1404. (g) For construction of steroidal side chains with natural and nonnatural configurations at C20 using palladium-catalyzed allylic alkylation, see: (h) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1976, 98, 630. (i) Trost, B. M.; Matsumura, Y. J. Org. Chem. 1977, 42, 2036. (j) Trost, B. M.; Verhoeven, T. R. J. Am. Chem. Soc. 1978, 100, 3435.
23. For the stereochemistry of alkylation of allylic carbamates with cuprates, see: (a) Gallina, C.; Ciattini, P. G. J. Am. Chem. Soc. 1979, 101, 1035. (b) Gallina, C. Tetrahedron Lett. 1982, 23, 3093. (c) Goering, H. L.; Kantner, S. S.; Tseng, C. C. J. Org. Chem. 1983, 48, 715.
24. For the stereochemistry of alkylation of allylic carbamates with cuprates, see: (a) Gallina, C.; Ciattini, P. G. J. Am. Chem. Soc. 1979, 101, 1035. (b) Gallina, C. Tetrahedron Lett. 1982, 23, 3093. (c) Goering, H. L.; Kantner, S. S.; Tseng, C. C. J. Org. Chem. 1983, 48, 715.
25. For the stereochemistry of alkylation of allylic carbamates with cuprates, see: (a) Gallina, C.; Ciattini, P. G. J. Am. Chem. Soc. 1979, 101, 1035. (b) Gallina, C. Tetrahedron Lett. 1982, 23, 3093. (c) Goering, H. L.; Kantner, S. S.; Tseng, C. C. J. Org. Chem. 1983, 48, 715.
26. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
27. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
28. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
29. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
30. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
31. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
32. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
33. For reviews on the synthesis of vitamin D metabolites and analogues, see: (a) Pardo, R.; Santelli, M. Bull. Soc. Chim. Fr. 1985, 98. (b) Quinkert, G. Vitamin D Active Compounds. Part I. Synform 1985, 3, 41; (c) Part II. Ibid. 1986, 4, 131; (d) Part III. Ibid. 1987, 5, 1. (e) Wilson, S. R.; Yasmin, A. Stereoselective Synthesis of Vitamin D. In Studies in Natural Products Chemistry; Atta-ur-Rahman., Ed.; Elsevier: Amsterdam, 1992; Vol. 10, p 43. (f) Dai, H.; Posner, G. H. Synthesis 1994, 1383. (g) Schmalz, H.-G. Nachr. Chem. Tech. Lab. 1994, 42, 397. (h) Zhu, G.-D.; Okamura, W. H. Chem. Rev. 1995, 95, 1877.
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36. 1H NMR of the crude reaction mixture.
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48. 3, 250 MHz): 30, δ = 6.09, 6.16 (2 H, J = 11.2 Hz, H6 and H7); 31, δ = 5.95; 6.48 (2 H, J = 11.3 Hz, H6 and H7).
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51. Ketone 32d (X = OCONHPh, Y = O, Scheme 10) was prepared in 83% overall yield by the sequence: 9a → 35a (X = OH, Y = -OH) → 35d (X = OCONHPh, Y = -OH).
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60. The starting cyclopropyllithium was prepared from cyclopropyl bromide and tert-butyllithium.