A Concise Route to Structurally Diverse DMP 323 Analogues via Highly Functionalized 1,4-Diamines

Organic Letters

Volumn 4, Issue 26, 2002, Pages 4673-4676

  McReynolds, Matthew D ^a   Sprott, Kevin T ^a   Hanson, Paul R ^a  

^a UNIVERSITY OF KANSAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

4,7 DIBENZYL 2,3,4,5,6,7 HEXAHYDRO 5,6 DIHYDROXY 1,3 BIS[4 (HYDROXYMETHYL)BENZYL] 2H 1,3 DIAZEPIN 2 ONE; ALCOHOL DERIVATIVE; DIAMINE; DRUG DERIVATIVE; HETEROCYCLIC COMPOUND; PROTEINASE INHIBITOR; UREA;

ARTICLE; CHEMISTRY; SYNTHESIS;

ALCOHOLS; DIAMINES; HETEROCYCLIC COMPOUNDS; HIV PROTEASE INHIBITORS; UREA;

EID: 0142201199     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol027074v     Document Type: Article

References (52)

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9. For use of tethers in RCM reactions, see: (a) O'Leary, D. J.; Miller, S. J.; Grubbs, R. H. Tetrahedron Lett. 1998, 39, 1689-1690. (b) Evans, P. A.; Murthy, V. S. J. Org. Chem. 1998, 63, 6768-6769. (c) Hoye, T. R.; Promo, M. A. Tetrahedron Lett. 1999, 40, 1429-1432. (d) Gierasch, T. M.; Chytil, M.; Didiuk, M. T.; Park, J. Y.; Urban, J. J.; Nolan, S. P.; Verdine, G. L. Org. Lett. 2000, 2, 3999-4002. (d) Rodriguez, J. R.; Castedo, L.; Mascarenas, J. L. Org. Lett. 2000, 2, 3209-3212. (e) Sprott, K. T.; Hanson, P. R. J. Org. Chem. 2000, 65, 7913-7918. (f) Sakamoto, Y.; Okazaki, M.; Miyamoto, K.; Nakata, T. Tetrahedron Lett. 2001, 42, 7633-7636. (g) Micalizio, G. C.; Schreiber, S. L. Angew. Chem., Int. Ed. 2002, 41, 152-154.
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11. For use of tethers in RCM reactions, see: (a) O'Leary, D. J.; Miller, S. J.; Grubbs, R. H. Tetrahedron Lett. 1998, 39, 1689-1690. (b) Evans, P. A.; Murthy, V. S. J. Org. Chem. 1998, 63, 6768-6769. (c) Hoye, T. R.; Promo, M. A. Tetrahedron Lett. 1999, 40, 1429-1432. (d) Gierasch, T. M.; Chytil, M.; Didiuk, M. T.; Park, J. Y.; Urban, J. J.; Nolan, S. P.; Verdine, G. L. Org. Lett. 2000, 2, 3999-4002. (d) Rodriguez, J. R.; Castedo, L.; Mascarenas, J. L. Org. Lett. 2000, 2, 3209-3212. (e) Sprott, K. T.; Hanson, P. R. J. Org. Chem. 2000, 65, 7913-7918. (f) Sakamoto, Y.; Okazaki, M.; Miyamoto, K.; Nakata, T. Tetrahedron Lett. 2001, 42, 7633-7636. (g) Micalizio, G. C.; Schreiber, S. L. Angew. Chem., Int. Ed. 2002, 41, 152-154.
12. For use of tethers in RCM reactions, see: (a) O'Leary, D. J.; Miller, S. J.; Grubbs, R. H. Tetrahedron Lett. 1998, 39, 1689-1690. (b) Evans, P. A.; Murthy, V. S. J. Org. Chem. 1998, 63, 6768-6769. (c) Hoye, T. R.; Promo, M. A. Tetrahedron Lett. 1999, 40, 1429-1432. (d) Gierasch, T. M.; Chytil, M.; Didiuk, M. T.; Park, J. Y.; Urban, J. J.; Nolan, S. P.; Verdine, G. L. Org. Lett. 2000, 2, 3999-4002. (d) Rodriguez, J. R.; Castedo, L.; Mascarenas, J. L. Org. Lett. 2000, 2, 3209-3212. (e) Sprott, K. T.; Hanson, P. R. J. Org. Chem. 2000, 65, 7913-7918. (f) Sakamoto, Y.; Okazaki, M.; Miyamoto, K.; Nakata, T. Tetrahedron Lett. 2001, 42, 7633-7636. (g) Micalizio, G. C.; Schreiber, S. L. Angew. Chem., Int. Ed. 2002, 41, 152-154.
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21. For recent reviews, see: (a) Trnka, T. M.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18-29. (b) Fürstner, A. Angew. Chem., Int. Ed. 2000, 39, 3013-3043. (c) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413-4450. (d) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371-388.
22. Sprott, K. T.; McReynolds, M. D.; Hanson, P. R. Org. Lett. 2001, 3, 3939-3942. All 1,4-diamines described in this manuscript were prepared using this protocol.
23. We have also reported the synthesis of 1,4-diamines via a phthalamide tether/RCM/hydrolysis sequence; see ref 2e.
24. Lam, P. Y. S.; Jadhav, P. K.; Eyermann, C. J.; Hodge, C. N.; Ru, Y.; Bachelor, L. T.; Meek, J. L.; Otto, M. J.; Rayner, M. M.; Wong, Y. N.; Chang, C.-H.; Weber, P. C.; Jackson, D. A.; Sharpe, T. R.; Erickson-Vittanen, S. Science 1994, 263, 380-384.
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27. (b) Pierce, M. E.; Harris, G. D.; Islam, Q.; Radesca, L. A.; Storace, L.; Waltermire, R. E.; Wat, E.; Jadhav, P. K.; Emmett, G. C. J. Org. Chem. 1996, 61, 444-450.
28. (c) Confalone, P. N.; Waltermire, R. E. In Process Chemistry in the Pharmaceutical Industry; Gadamasetti, K. G., Ed.; Marcel Dekker: New York, 1999; pp 201-219.
29. For evalutation of P1/P1′ substituents, see: (a) Nugiel, D. A.; Jacobs, K.; Cornelius, L.; Chang, C.-H.; Jadhav, P. K.; Holler, E. R.; Klabe, R. M.; Bacheler, L. T.; Cordova, B.; Garber, S.; Reid, C.; Logue, K. A.; Gorey-Feret, L. J.; Lam, G. N.; Erickson-Vittanen, S.; Seitz, S. P. J. Med. Chem. 1997, 40, 1465-1474. (b) Patel, M.; Bacheler, L. T.; Rayner, M. M.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1998, 8, 823-828. For evalutation of P2/P2′ substituents, see: (c) Han, Q.; Chang, C.-H.; Li, R.; Ru, Y.; Jadhav, P. K.; Lam, P. Y. S. J. Med. Chem. 1998, 41, 2019-2028. (d) Rodgers, J. D.; Johnson, B. L.; Wang, H.; Erickson-Viitanen, S.; Klabe, R. M.; Bacheler, L.; Cordova, B. C.; Chang, C.-H. Bioorg. Med. Chem. Lett. 1998, 8, 715-720.
30. For evalutation of P1/P1′ substituents, see: (a) Nugiel, D. A.; Jacobs, K.; Cornelius, L.; Chang, C.-H.; Jadhav, P. K.; Holler, E. R.; Klabe, R. M.; Bacheler, L. T.; Cordova, B.; Garber, S.; Reid, C.; Logue, K. A.; Gorey-Feret, L. J.; Lam, G. N.; Erickson-Vittanen, S.; Seitz, S. P. J. Med. Chem. 1997, 40, 1465-1474. (b) Patel, M.; Bacheler, L. T.; Rayner, M. M.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1998, 8, 823-828. For evalutation of P2/P2′ substituents, see: (c) Han, Q.; Chang, C.-H.; Li, R.; Ru, Y.; Jadhav, P. K.; Lam, P. Y. S. J. Med. Chem. 1998, 41, 2019-2028. (d) Rodgers, J. D.; Johnson, B. L.; Wang, H.; Erickson-Viitanen, S.; Klabe, R. M.; Bacheler, L.; Cordova, B. C.; Chang, C.-H. Bioorg. Med. Chem. Lett. 1998, 8, 715-720.
31. For evalutation of P1/P1′ substituents, see: (a) Nugiel, D. A.; Jacobs, K.; Cornelius, L.; Chang, C.-H.; Jadhav, P. K.; Holler, E. R.; Klabe, R. M.; Bacheler, L. T.; Cordova, B.; Garber, S.; Reid, C.; Logue, K. A.; Gorey-Feret, L. J.; Lam, G. N.; Erickson-Vittanen, S.; Seitz, S. P. J. Med. Chem. 1997, 40, 1465-1474. (b) Patel, M.; Bacheler, L. T.; Rayner, M. M.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1998, 8, 823-828. For evalutation of P2/P2′ substituents, see: (c) Han, Q.; Chang, C.-H.; Li, R.; Ru, Y.; Jadhav, P. K.; Lam, P. Y. S. J. Med. Chem. 1998, 41, 2019-2028. (d) Rodgers, J. D.; Johnson, B. L.; Wang, H.; Erickson-Viitanen, S.; Klabe, R. M.; Bacheler, L.; Cordova, B. C.; Chang, C.-H. Bioorg. Med. Chem. Lett. 1998, 8, 715-720.
32. For evalutation of P1/P1′ substituents, see: (a) Nugiel, D. A.; Jacobs, K.; Cornelius, L.; Chang, C.-H.; Jadhav, P. K.; Holler, E. R.; Klabe, R. M.; Bacheler, L. T.; Cordova, B.; Garber, S.; Reid, C.; Logue, K. A.; Gorey-Feret, L. J.; Lam, G. N.; Erickson-Vittanen, S.; Seitz, S. P. J. Med. Chem. 1997, 40, 1465-1474. (b) Patel, M.; Bacheler, L. T.; Rayner, M. M.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1998, 8, 823-828. For evalutation of P2/P2′ substituents, see: (c) Han, Q.; Chang, C.-H.; Li, R.; Ru, Y.; Jadhav, P. K.; Lam, P. Y. S. J. Med. Chem. 1998, 41, 2019-2028. (d) Rodgers, J. D.; Johnson, B. L.; Wang, H.; Erickson-Viitanen, S.; Klabe, R. M.; Bacheler, L.; Cordova, B. C.; Chang, C.-H. Bioorg. Med. Chem. Lett. 1998, 8, 715-720.
33. i = 3.6 nM); see: Kaltenbach, R. F., III; Nugiel, D. A.; Lam, P. Y. S.; Klabe, R. M.; Seitz, S. P. J. Med. Chem. 1998, 41, 5113-5117.
34. De Lucca, G. V J. Org. Chem. 1998, 63, 4755-4766.
35. Hultén, J.; Bonham, N. M.; Nillroth, U.; Hansson, T.; Zuccarello, G.; Bouzide, A.; Åqvist, J.; Classon, B.; Danielson, U. H.; Karlén, A.; Kvarnström, I.; Samuelsson, B.; Hallberg, A. J. Med. Chem. 1997, 40, 885-897.
36. (b) Hultén, J.; Andersson, H. O.; Schaal, W.; Danielson, H. U.; Classon, B.; Kvarnström, I.; Karlén, A.; Unge, T.; Samuelsson, B.; Hallberg, A. J. Med. Chem. 1999, 42, 4054-4061.
37. Schaal, W.; Karlsson, A.; Ahlsen, G.; Lindberg, J.; Andersson, H. O.; Danielson, U. H.; Classon, B.; Unge, T.; Samuelsson, B.; Hultén, J.; Hallberg, A.; Karlén, A. J. Med. Chem. 2001, 44, 155-169.
38. Unsymmetric DMP 323 derivatives are of particular interest due to their potential to exhibit different solubility and inhibitory profiles relative to their C2-symmetric counterparts; see: (a) Wilkerson, W. W.; Dax, S.; Cheatham, W. W. J. Med. Chem. 1997, 40, 4079-4088. (b) De Lucca, G. V.; Kim, U. T.; Liang, J.; Cordova, B.; Klabe, R. M.; Garber, S.; Bacheler, L. T.; Lam, G. N.; Wright, M. R.; Logue, K. A.; Erickson-Viitanen, S.; Ko, S. S.; Trainor, G. L. J. Med. Chem. 1998, 41, 2411-2423. (c) Patel, M.; Kaltenbach, R. F., III; Nugiel, D. A.; McHugh, R. J., Jr.; Jadhav, P. K.; Bacheler, L. T.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S.; Garber, S.; Reid, C.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1998, 8, 1077-1082.
39. Unsymmetric DMP 323 derivatives are of particular interest due to their potential to exhibit different solubility and inhibitory profiles relative to their C2-symmetric counterparts; see: (a) Wilkerson, W. W.; Dax, S.; Cheatham, W. W. J. Med. Chem. 1997, 40, 4079-4088. (b) De Lucca, G. V.; Kim, U. T.; Liang, J.; Cordova, B.; Klabe, R. M.; Garber, S.; Bacheler, L. T.; Lam, G. N.; Wright, M. R.; Logue, K. A.; Erickson-Viitanen, S.; Ko, S. S.; Trainor, G. L. J. Med. Chem. 1998, 41, 2411-2423. (c) Patel, M.; Kaltenbach, R. F., III; Nugiel, D. A.; McHugh, R. J., Jr.; Jadhav, P. K.; Bacheler, L. T.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S.; Garber, S.; Reid, C.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1998, 8, 1077-1082.
40. Unsymmetric DMP 323 derivatives are of particular interest due to their potential to exhibit different solubility and inhibitory profiles relative to their C2-symmetric counterparts; see: (a) Wilkerson, W. W.; Dax, S.; Cheatham, W. W. J. Med. Chem. 1997, 40, 4079-4088. (b) De Lucca, G. V.; Kim, U. T.; Liang, J.; Cordova, B.; Klabe, R. M.; Garber, S.; Bacheler, L. T.; Lam, G. N.; Wright, M. R.; Logue, K. A.; Erickson-Viitanen, S.; Ko, S. S.; Trainor, G. L. J. Med. Chem. 1998, 41, 2411-2423. (c) Patel, M.; Kaltenbach, R. F., III; Nugiel, D. A.; McHugh, R. J., Jr.; Jadhav, P. K.; Bacheler, L. T.; Cordova, B. C.; Klabe, R. M.; Erickson-Viitanen, S.; Garber, S.; Reid, C.; Seitz, S. P. Bioorg. Med. Chem. Lett. 1998, 8, 1077-1082.
41. We have developed a direct RCM route to both sulfamide and phosphonamide analogues of 6. For sulfamide derivative, see: Dougherty, J. M.; Probst, D. A.; Robinson, R. E.; Moore, J. D.; Klein, T. A.; Snelgrove, K. A.; Hanson, P. R. Tetrahedron 2000, 56, 9781-9790. For phosphonamide derivative, see ref 3c.
42. Since 4c was completely consumed during the course of this reaction, the low isolated yield of 8 could be attributed to competing oligomer formation: see: McCusker, J. E.; Grasso, C. A.; Main, A. D.; McElwee-White, L. Org. Lett. 1999, 1, 961-964.
43. 2 is a notoriously poor electrophile toward secondary amines; see: Barluenga, J.; Lopez-Ortiz, J. F.; Tomas, M.; Gotor, V. J. Chem. Soc., Perkin Trans. 1 1981, 1891-1895.
44. We postulate that the steric congestion of the 1,4-diamines 4c,e-g, as well as subtle steric and electronic differences in the electrophiles, contribute to the failure of this reaction. See refs 2e and 17.
45. For our direct RCM strategy to generate cyclic sulfamides analogous to 12 and related to 14, see ref 15.
46. We initially believed that the phosphonyl moiety could serve as a stereodirecting group to augment the inherent diastereofacial bias for dihydroxylation anti to the isopropyl group.
47. 31P NMR correlation experiment, as well as X-ray data for major-16c.
48. 2].
49. X-ray data for 1d can be found in the Supporting Information.
50. Preliminary molecular modeling experiments (SYBYL v. 6.8 using MMFF94 force field: see Supporting Information) suggest that N-substitution effects the orientation of the endocyclic isopropyl group in cyclic sulfamide 14, leading to diminished diastereoselectivity.
51. Molecular modeling experiments similar to those described in ref 24 suggest that significant conformational changes in the seven-membered ring may lead to the observed differences in diastereoselectivity between major-16a and minor-16a.
52. Dupau, P.; Epple, R.; Thomas, A. A.; Fokin, V. V.; Sharpless, K. B. Adv. Synth. Catal. 2002, 344, 421-433.