Core Ring Structures

It is generally understood that smectic liquid crystals are more likely to be formed in systems where the central core region has aromatic or heteroaromatic ring structures. Alicyclic ring systems, conversely, tend to disfavour smectic phase formation, see Fig. 15 for relative ordering, and in particular, they tend to depress tilted phases over orthogonal phases. 

For example, early work in the search for nematic materials for display devices resulted in development of the 4-substituted-phe-nyl benzoate unit as a suitable core for imparting mesogenic properties to a material 

Decreasing ability to form smectic phases Increasirtg preference for orthogonal phases 

Usually the core system in smectogens contains a linking group positioned either between two ring units or between a ring and an aliphatic chain. The linking group has been shown to have marked effects on 

Lateral substituents may be attached to the core system or located in the terminal aliphatic chain. By and large, lateral substituents positioned on the core or in the terminal chain(s) disfavour smectic mesophase formation. Smectic mesophase formation is principally depressed more by the steric bulk of the lateral group than by its polarity. Thus for example, fluoro substituents at the core or in the chain(s) are less effective at depressing smectic mesophase formation than is a methyl substituent [14, 31], nevertheless fluoro substitution still lowers transition temperatures of the phase transition to the smectic state in comparison to the unsubstituted analogue. 

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When grouped on the basis of similarities in their chemical structure, most antibiotics fall into the categories listed in Table 1.17. S-Lactams, which include penicillins and cephalosporins, exhibit a characteristic /i-lactam core ring structure (a four-atom cyclic amide) (Figure 1.14). They induce their bacteriocidal activity by inhibiting the synthesis of peptidoglycan, an essential component of the bacterial cell wall. 

Penicillins refer to a family of both natural and semi-synthetic antibiotics. Although all exhibit a 6-aminopenicillanic acid core ring structure (Figure 1.15), they differ in the structure of their side-chains. Naturally produced penicillins include penicillins G and V. Semi-synthetic penicillins can be manufactured by enzymatic removal of a natural penicillin side-chain (using... 

Tetracyclines are a family of antibiotics which display a characteristic 4-fused-core ring structure (Figure 1.16). They exhibit broad antimicrobial activity and induce their effect by inhibiting protein synthesis in sensitive microorganisms. Chlortetracycline was the first member of this family to be discovered (in 1948). Penicillin G and streptomycin were the only antibiotics in use at that time, and chlortetracycline was the first antibiotic employed therapeutically that retained its antimicrobial properties upon oral administration. Since then, a number of additional tetracyclines have been discovered (all produced by various strains of Streptomyces), and a variety of semi-synthetic derivatives have also been prepared (Table 1.18). 

Figure 3.24. Monosaccharides that commonly constitute the carbohydrate portion of glycoproteins. Refer to text for details. Note that individual hydrogen atoms attached to the core ring structure are omitted for clarity of presentation...

Figure 4 Core ring structures common among drugs and related molecules. From ref. 25.

Speed manufacturers need only look at the molecules and imagine them without those extra OHs or methylenedioxy ring structures attached to the benzene core. These particular pathways are, however, more uniquely suited for X precursor production because they take advantage of the hindrance that methylenedioxy ring structures and OHs provide on one side of the benzene core. This helps to better assure that mono chloromethylations or bro-minations will occur whereas di- and tri-substitutions are possible on a naked benzene molecule which speed chemists are going to be using (please don t ask). 

The Boger pyrrole synthesis based on a heterocyclic azadiene Diels-Alder strategy (1,2,4,5-tetrazine to 2,2-diazine to pyrrole) was employed by the author for the total synthesis of ningalin B . Thus a Diels-Alder reaction of the electron-rich acetylene 52 with the electron deficient 1,2,4,5-tetrazine 53 proceeded to give the desired diazine 54 which underwent subsequent ring contraction to afford the core pyrrole structure 55. 

Furthennore, resonance Raman studies of aconitase by Johnson et al. (53) demonstrated homologous spectra for both inactive and active aconitase. This suggests similar vibrational modes and thus similar core structures for the two forms. Finally, a cubane structure for the [3Fe-4S] cluster is supported by recent protein crystallographic studies of inactive aconitase by Robbins and Stout (54). (Recent results from Jensen s group (55) on the redetermination of the crystal structure of the Azotobacter ferredoxin I clearly show that the 3Fe cluster does not have a [3Fe-3S] ring structure, as originally determined (37), but has a [3Fe-4S] cubane structure.)... 

As can be observed, the group of thyroid hormone receptors (1 A) is represented by molecular scaffolds of low structural complexity, with at most a single ring in the core ring system. In this respect, the scaffold simplicity of the molecules annotated to this group contrasts with the wide diversity of scaffolds found in the other two nuclear receptor groups. For example. 

Ansamycins, like the macrolides, are synthesized by condensation of a number of acetate and propionate units. These antibiotics, which are produced by several genera of the Actinomy-cetales, display a characteristic core aromatic ring structure. Amongst the best-known family members are the rifamycins, which are particularly active against Gram-positive bacteria and mycobacteria. They have been used, for example, in the treatment of Mycobacterium tuberculosis. 

These BCAs chelate metal atoms by holding them in the center of their nitrogenous ring structure, in a manner similar to the chelation of iron at the core of a porphyrin prosthetic group. The excellent stability of this complex allows the use of DOTA, NOTA, and TETA conjugates in vivo with minimal potential for leaching and deleterious side effects. 

The search for improved methods for the formation of ring structures is and always has been at the core of organic chemistry research [19]. This drive has led to the extensive investigation of the RCM reaction and its acceptance as one of the most facile, flexible and selective cyclisation methodologies in the contemporary chemist s repertoire. (A scifinder 2002 search found over 1,400 pa-... 

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