A stereocontrolled approach to substituted piperidones and piperidines: flavopiridol D-ring analogs

Author:

Gross Alexandre,Borcherding David R,Friedrich Dirk,Sabol Jeffrey S

Publisher

Elsevier BV

Subject

Organic Chemistry,Drug Discovery,Biochemistry

Reference9 articles.

1. Cyclin-Dependent Kinase Inhibitors:  Useful Targets in Cell Cycle Regulation

2. Sedlacek, H. H.; Czech, J.; Naik, R.; Kaur, G.; Worland, P.; Losiewicz, M.; Parker, B.; Carlson, B.; Smith, A. Int. J. Oncol. 1996, 9, 1143–1168.

3. Simple stereoselective version of the Claisen rearrangement leading to trans-trisubstituted olefinic bonds. Synthesis of squalene

4. STEREOCONTROLLED IODOLACTONIZATION OF ACYCLIC OLEFINIC ACIDS: THE trans AND cis ISOMERS OF 4,5-DIHYDRO-5-IODOMETHYL-4-PHENYL-2(3H)-FURANONE

5. Selected NMR data: 5 1H NMR (400 MHz, CDCl3): δ 6.15 s (2H; H-3′/H-5′), 4.80 ddd (J=9.5, 5.5, 3 Hz; H-4α), 3.82 s (3H; 4′-OMe), 3.80 s (6H; 2′-OMe/6′-OMe), 3.69 dd (J=11, 9.5 Hz; H-3β), 3.44 dd (J=13.5, 3 Hz; H-5), 3.33 dd (J=13.5, 5.5 Hz; H-5), 3.32 dq (J=11, 7 Hz; H-2α), significant NOE between H-2α and H-4α. 6 1H NMR (400 MHz, CDCl3): δ 6.18 s (2H; H-3′/H-5′), 5.86 brs (NH), 4.12 brs (4α-OH), 4.08 brs (H-4β), 3.82 s (9H; 2′-OMe/4′-OMe/6′-OMe), 3.72 dd (J=12, 1.5 Hz; H-3β), 3.50 brdd (J=12.5, 2.5 Hz; H-5β), 3.37 ddd (J=12.5, 3.5, 2.5 Hz; H-5α), 3.33 dq (J=12, 7 Hz; H-2α), 1.04 d (3H; J=7 Hz; H-6), NOEs between axial H-2α and 4α-OH, and between axial H-3β and H-5β. 10 1H NMR (500 MHz, CDCl3): δ 7.55 dd (J=8, 1.5 Hz; H-6″), 7.54 dd (J=7.5, 2 Hz; H-3″), 7.48 ddd (J=8, 7.5, 2 Hz; H-5″), 7.42 ddd (J=7.5, 7.5, 1.5 Hz; H-4″), 6.40 s (H-3′), 6.30 s (H-7′), 4.15 brs (H-3β), 3.16 dd (J=12, 1 Hz; H-4β), 3.09 brd (J=12 Hz; H-2α), 3.05 brd (J=11.5 Hz; H-6α), 2.85 dddq (J=12, 11, 4, 6.5 Hz; H-5α), 2.46 s (3H; N-CH3), 2.41 brd (J=12 Hz; H-2β), 1.94 dd (J=11.5, 11 Hz; H-6β), 0.65 d (3H; J=6.5 Hz; H-7). 11 1H NMR (300 MHz, CDCl3); δ 6.18 s (2H; H-3′/H-5′), 5.72 brs (NH), 4.16 brs (4α-OH), 3.97 ddd (J=13, 6, 1 Hz; H-3β), 3.82 s (6H; 2′-OMe/6′-OMe), 3.81 s (3H; 4′-OMe), 3.80 brs (H-4β), 3.65 brdq (J=2, 6.5 Hz; H-5β), 3.24 dd (J=18, 13 Hz; H-2α), 2.28 dd (J=18, 6 Hz; H-2β), 1.27 d (3H; J=6.5 Hz; H-6), NOEs between axial H-2α and 4α-OH, and between axial H-3β and H-5β. 12 1H NMR (500 MHz, CDCl3): δ 7.57 ddd (J=7.5, 2, 0.5 Hz; H-3″), 7.56 ddd (J=8, 1.5, 0.5 Hz; H-6″), 7.49 ddd (J=8, 7.5, 2 Hz; H-5″), 7.43 ddd (J=7.5, 7.5, 1.5 Hz; H-4″), 6.42 s (H-3′), 6.31 s (H-7′), 3.85 brs (H-3β), 3.63 ddd (J=13, 4.5, 1.5 Hz; H-4β), 3.08 m (H-6α), 2.58 m (H-5α), 2.45 brq (J=6.5 Hz; H-2β), 2.41 s (3H; N-CH3), 2.40 m (H-6β), 1.54 m (H-5β), 1.26 d (3H; J=6.5 Hz; H-7), NOEs between axial H-4β and axial H-2β, H-6β.

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