Cyclohexene scaffold

An example is provided by a series of neuraminidase inhibitors leading to the design of the avian flu agent tamiflu. These compounds result from a cyclohexene scaffold containing lipophilic side-chains. ... 

A Sialidase Inhibitor Based on a Cyclohexene Scaffold The Development of Oseltamivir... 

As shown in the scheme above, cyclohexene scaffolds are easily produced in MBFTs with the aid of the three-component approach. Hong and coworkers, however, managed the generation of the very similar cyclohexadiene scaffold by using only one starting material [15]. The asymmetric dimerization reaction is facilitated by proline in another enamine/iminium approach, but now in repeat (Scheme 14.7). This enantioselective Robinson annulation approach provides the opportunity to explore a new route to (-l-)-palitantin, an antiprotozoal and antifungal agent [16]. 

Whereas cyclohexene or benzene ring systems are intuitively apparent mimics of Neu5Ac2en and related inhibitors, it is less obvious that five-membered ring systems can play the same role. However, it has been demonstrated that compounds based on different five-membered cyclic scaffolds can engage each of the identified subsites (S1-S5) of influenza virus NA, affording potent inhibitory activity. 

Figure 8.8 Scaffold (cyclohexene) hierarchy derived from mutagenicity dataP8] The proportion of Ames negative to Ames positive counts is qualitatively indicated below each scaffold. The confidence interval of the proportions is shown on the right of the scaffolds. Data taken from Kho et al.[3 I...

This process is an important tool in synthetic organic photochemistry for the preparation of small rings. The difficulties in the preparation of medium-size and larger cyclic compounds, caused by entropic factors, have been circumvented by the presence of a rigid molecular scaffold (cyclopropanes, aromatic rings, cyclohexenes and cis-alkenes), which prevents hydrogen abstraction from positions close to the carbonyl group (Scheme 9.39) [64—66]. 

Construction of the Dolby model system began with epoxidation of cyclohexene 209 employing mCPBA in chloroform. The epoxide product was then subjected to a base-promoted cyclization via amide deprotonation and oxirane opening to provide benzamide 210 (Scheme 23). Hydroxyl oxidation using the Jones conditions next furnished cyclohexanone 211. A Fischer indole synthesis on this scaffold, followed by amine deprotection using sodium hydroxide, led to the desired l,3-(iminoethano)carbazole 83. While the yield of this route was low, it was the first example of a method to fashion the 2-azabicyclo[3.3.1]nonan-8-one system 211, and importantly demonstrated that indoHzation on such a scaffold was possible. 

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