Tetrahydroquinoline-based

Fig. 8. Thymidylate synthase inhibitors designed to fit into the A/, AJ -methylenetetrahydrofolate binding site. The best inhibitors from each class are the classical antifolate TS inhibitor (31), the naphthostyril-based lead compound (32), and the tetrahydroquinoline-based lead compound (33), iC values (in nAI)...

Figure 15.22 Stereoselective DOS approach to tetrahydroquinoline-based natural product-like polycydics by Arya et al. [58].

Figure 15.23 Tetrahydroquinoline-based p-amino acids synthesized by an asymmetric hetero-Michael approach.

Figure 15.25 Model studies regio and stereoselective hetero-Michael approach to tetrahydroquinoline-based polycyclics.

Figure 15.26 Stereocontrolled solid-phase synthesis of tetrahydroquinoline-based natural-product-like polycyclics.

Fig. 17.9 Modular solid phase approaches to obtain tetrahydroquinoline-based different tricyclic compounds containing macrocyclic rings, (a) (i) 4-pentenoic acid, DMAP, DIC (ii) 20% piperidine (iii) trans-crotonoyl...

As a final illustration, an unprecedented approach was discovered, wherein an in situ aza-Michael reaction was used that allowed the development of bridged tetrahydroquinoline-based tricyclic architectures under very mild reaction conditions [30]. In a typical example, enantio-enriched compound 52 (Figure 17.12) was converted to 53 in a series of steps. Following the acetonide and the N-Alloc removal, to our surprise there was no sign of the free amine derivative 54. Instead, compound 55 was obtained as single diastereomer. Under these mild reaction conditions, the in situ aza-Michael cyclization produced the bridged architectures. 

Fig. 17.11 Solution and solid phase approaches to obtain tetrahydroquinoline-based tricyclic compounds having medium sized unsaturated lactams, (a) (i) LiBH4, THF, RT (ii) Dess-Martin priodinane, RT (iii) ZnCl2, AllylMgBr, -78 °Q (iv) AcjO, DMAP, CHjClj, 0°C to RT.

Fig. 17.12 In situ bridged aza Michael approach in solution and on solid phase to obtain tetrahydroquinoline-based tricyclic compounds, (a) (i) acetic acid/THF/H20, RT (ii) TESOTf, pyridine, CH2CI2, -40°C (iii) Pd(PPh3)4, morpholine, CH2CI2, RT (c) Et3N, benzoyl chloride or cinnamoyl chloride, CH2CI2, O C to RT.

Yehia NAM, Polbom K, Muller TJJ (2002) A novel four component one-pot access to pyrindines and tetrahydroquinolines based upon a coupling-isomerization sequence. Tetrahedron Lett 43 6907-6910... 

Novel, tetrahydroquinoline-based A/,S-type ligands were prepared by the Krohnke pyridine synthesis and their... 

Despite the early recognition that heterocyclic azadiene systems are typically electron-deficient,1 little effort has been devoted to the exploration of the potential participation of electron-deficient oxazoles in inverse electron demand (LUMOdiene controlled) Diels-Alder reactions with electron-rich or simple olefinic dienophiles. One study has demonstrated the potential of such investigations (Table 10-1, entry 26).34 Breslow and coworkers have adapted the oxazole olefin Diels-Alder reaction for the preparation of a tetrahydroquinoline-based analog of pyridoxamine with the stereochemically defined placement of a catalytic group [Eq. (2)].37b... 

Arya, P. et al., Solution- and solid-phase synthesis of natural product-like tetrahydroquinoline-based... 

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