Analogs Structure and Synthetic Efforts

Daliavalie S, Merlini L (2005) In Fattorasso E, Taglialatela-Scafati O (eds) Modem alkaloids. Wiley, Weinheim (Camptothecin and Analogs Structure and Synthetic Efforts)... 

The interest in azacyclooctatetraenes is mainly due to their structural similarity to cycloocta-tetraene.1 3 Most synthetic efforts have concentrated on a comparison of the unusual chemical and physical properties of cyclooctatetraene with its aza analogs. Besides studies concerning the aromaticity, the primary focus of much work has concerned the stability of the eight-membered ring and its valence isomerization. 

In studies of analogs of the redox cofactor pyrroloquinoline quinone (PQQ), synthetic efforts have focused initially on isosteric, isomeric structures that reflect on important mechanisms of electron-transfer catalysis mediated by PQQ. These studies provide insight into the choice of PQQ as an electron-transfer catalyst in nature, and bear directly on pharmaceutical applications of this vitamin-like nutritional factor. 

Many other variations of the basic structure 10 have been explored, including an-hydro sugars and carbocyclic analogs, the latter derived from quinic acid 13 [23-26]. In summary, the preparation of these materials (e.g. 14-16) requires more synthetic effort than the fructose-derived ketone 10. Occasionally, e.g. when using 14, catalyst loadings can be reduced to 5% relative to the substrate olefin, and epoxide yields and selectivity remain comparable with those obtained by use of the fructose-derived ketone 10. Alternative ex-chiral pool ketone catalysts were reported by Adam et al. The ketones 17 and 18 are derived from D-mannitol and tartaric acid, respectively [27]. Enantiomeric excesses up to 81% were achieved in the epox-idation of l,2-(E)-disubstituted and trisubstituted olefins. 

Ultimate progress in the control of the primary structure of synthetic macromolecules might be expected if it were possible to develop a template type synthesis, in analogy to the polymerase chain reaction [27]. In spite of many efforts, no successful concept has yet been developed, which is no surprise regarding the complicated supramolecular interactions involved in the necessary steps, i.e. preorganization of the template, binding of the monomer, initiation and termination of the polymerization, and the release of the formed raacromolecule from the template [28,29]. 

Synthetic efforts focus on the molecular engineering of sensitisers that enhance charge separation at the oxide solution interface. The structural features of the dye should match the requirements for current rectification by analogy to the photofield effect in transistors, the gate for unidirectional electron flow from the electrolyte through the junction and into the oxide is opened by the photoexcitation of the sensitiser. The reverse charge flow, i.e. recapture of the electron by the electrolyte, could be impaired by judicious design of the sensitiser. The latter should form a... 

Spiroproline derivatives are of interest in biological studies as an inhibitor and mechanistic probe of prolyl-4-hydroxylase. To develop potent inhibitors of angiotensinconverting enzyme (ACE), lipophilic and sterically hindered spiroproline derivatives have been substituted in the structural framework of peptides. In addition, spiroprolines could offer interesting scaffold precursors, particularly in synthesis of combinatorial libraries of peptides. Earlier synthetic efforts aimed at spiroproline analogs involved building the proline nucleus on the structural backbone of the alicyclic system followed by resolution. We decided to try to expand the potential of our synthesis of spirocyclic compounds to pro-line derivatives, with the hitherto unknown 2-aza-spiro[4.4]-nonane carboxylic acid (124) derivative as the target. 

In this review, we briefly describe the structure and properties of natural nucleic acids before describing the efforts to modify and mimic their physical characteristics and hybridization self-assembly motif. Examples of analogs of nucleobase and backbone are presented as potential synthetic alternatives to the natural biopolymers. These analogs have the capacity to introduce new and innovative functionalities into natural systems or even create completely synthetic supramolecular complexes. 

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