Side-chain modified structure

In addition to analogs incorporating an olefinic double bond as a linker between the macrolactone ring and different types of heterocycles, we have also studied a new family of side-chain modified structures, which are characterized by rigidifica-tion of the entire side-chain manifold (exemplified for quinoline-based analogs 30 and 31). ... 

Hawker et al. 2001 Hawker and Wooley 2005). Recent developments in living radical polymerization allow the preparation of structurally well-defined block copolymers with low polydispersity. These polymerization methods include atom transfer free radical polymerization (Coessens et al. 2001), nitroxide-mediated polymerization (Hawker et al. 2001), and reversible addition fragmentation chain transfer polymerization (Chiefari et al. 1998). In addition to their ease of use, these approaches are generally more tolerant of various functionalities than anionic polymerization. However, direct polymerization of functional monomers is still problematic because of changes in the polymerization parameters upon monomer modification. As an alternative, functionalities can be incorporated into well-defined polymer backbones after polymerization by coupling a side chain modifier with tethered reactive sites (Shenhar et al. 2004 Carroll et al. 2005 Malkoch et al. 2005). The modification step requires a clean (i.e., free from side products) and quantitative reaction so that each site has the desired chemical structures. Otherwise it affords poor reproducibility of performance between different batches. 

This volume brings together most of these critical issues by highlighting recent advances in a number of core areas of peptidomimetic synthesis. Section 9 focuses on side-chain-modified peptides, Section 10 describes the preparation and use of a variety of peptide main-chain modifications. Combined side-chain- and main-chain-modified peptides are covered in Section 11. Finally, Section 12 provides chemistry leading to peptides incorporating secondary structure ((1- and y-turns, helices, p-sheets) mimetics and inducers. 

Fig. 4 Molecular structure of diblock copolymers and side-chain modified lipopolymers whose pressure-area isotherms are presented in Figs. 6 and 7, respectively. Diblock copolymers are poly(2-n-nonyl)-poly(2-methyl or 2-ethyl-2-oxazoline) (NxEy and NxMj,), where x and y denote the block sizes of the hydrophobic nonyl and hydrophilic oxazoline blocks. Side-chain modified lipopolymers, which contain short oligo-EG sidechains in each monomer of the lipopolymer to create a bottle-brush-like structure, are di-octadecanoyl-glycerol 2-(3 -methoxymonoethylene glycol)propyl-2-oxazoline (DiCigMEGOxn) and di-octadecanoyl-glycerol 2-(3 -methoxytiiethyleneglycol)propyl-2-oxazoline (DiCisTEGOxn) (adapted from [7,8])...

Fig. 6.4.8. Pairs of adjacent peptide planes can be used to define the backbone torsion angles. These peptide plane orientations are defined by a pair of dipolar interactions for each plane. Combinations of these diplanes leads to the development of an initial structure. In a similar way, initial side-chain conformations can be characterized from orientational constraints in the side-chain. (Modified version of figure from Ketchem et al. [27], reprinted with permission.)...

Much of the chemistry devoted to side-chain modified zanamivir analogues has been driven by a desire to prepare structurally simpler derivatives, especially from the viewpoint of easier chemical syntheses. Replacement of the glycerol side-chain of zanamivir with an achiral ether substituent has... 

Rathgeber S, Perlich J, KAhnlenz F, TArk S, Egbe DA, Hoppe H, et al. Correlation between polymer architecture, mesoscale structure and photovoltaic performance in side-chain-modified poly(p-arylene-ethynyl-ene)-alt-poly(p-arylene-vinylene) PCBM bulk-heterojunction solar cells. Polymer 2011 52(17) 3819-26. 

In a structure activity relationship study on polyether ionophore monensin 206, Still [44] prepared side-chain-modified analogues like compound 207 of the antibiotic by the orthoester rearrangement (Scheme 6.31). The stabihty of this complex polyether under the reaction conditions is worthy of note. 

In addition to these structures, other retinoids were synthesized with side chains modified by an oxygen functional group. When the C20 diol (490), a building block that is readily obtainable in an industrial synthesis of retinol (1) (Isler et al., 1949), was oxidized with manganese(IV) oxide, the ketoaldehyde (491) was obtained (Surmatis, 1972). 

Figure 24. Biomesogenic structures a) (Bio)meso-gens displaying order-disorder distributions in CPK-presentation (left to right and top to bottom) hexa-n-alkanoyl-oxybenzene discoid - Chandrasekar s first non-rodlike liquid crystal [28 a, 51c] enantiomeric cholesteric estradiol- and estrone-derivatives [ 17 a, c, d, 26 f, 51 a, s, u] Reinitzer s cholesterolbenzoate [21, 22] - together with the acetate the foundation stones of liquid crystal history [21, 22] Kelker s MBBA -first liquid crystal fluid at ambient temperature [ 13 f, g] Gray s cyanobiphenyl nematics for electrooptic displays [25 a, 51 e] lyotropic lecithin membrane component [7 a, 14, 27 d, 52 a] and valinomycin-K -membrane carrier [7 a, 35] thermotropic cholesteryl-side-chain-modified polysiloxanes with the combination of flexible main-chain and side-chain spacers [51 a, h] thermotropic azoxybenzene polymers with flexible main-chain spacers [51a] thermotropic cya-...

Ding, X., Vera, M.D., Liang, B., Zhao, Y., Leonard, M.S., and Joullie, M. M. (2001) Structure-activity relationships of side-chain modified didemnins. Bioorg. Med. Chem. Lett., 11,231-234. 

Cholesterol was isolated m the eighteenth century but its structure is so complex that Its correct constitution was not determined until 1932 and its stereochemistry not verified until 1955 Steroids are characterized by the tetracyclic ring system shown m Figure 26 9a As shown m Figure 26 9b cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C 3 a double bond at C 5 methyl groups at C 10 and C 13 and a C Hn side chain at C 17 Isoprene units may be discerned m var lous portions of the cholesterol molecule but the overall correspondence with the iso prene rule is far from perfect Indeed cholesterol has only 27 carbon atoms three too few for It to be classed as a tnterpene... 

Barhanin et al. (26) chemically modified the side chains of several residues to correlate structure and function in As II. Their results established the importance of charged residues for the function of the toxin. They showed that Arg-13 is essential for binding to the sodium channels as well as for toxicity, while the aspartate, glutamate, and lysine residues in the N-terminal segment of the protein are... 

Most relevant for the affinity for A9-THC and analogs to CB-receptors are the phenolic hydroxyl group at C-1, the kind of substitution at C-9, and the properties of the side chain at C-3. Relating to the structure-activity relationships (SAR) between cannabinoids and the CB-receptors, many different modified strucfures of fhis subsfance group were developed and fesfed. The most important variations include variations of the side chain at the olivetolic moiety of the molecules and different substitutions at positions C-11 and C-9. One of the most popular analogous compounds of A9-THC is HU-210 or (-)-trans-ll-OH-A8-THC-DMH, a cannabinoid with a F,l-dimethylheptyl side... 

In designing studies of the structure-activity relationships of MDMA and related substances, there are at least three areas for structural modification. First, the nature of the amine substituents can be varied other N-alkyls can be studied, or the nitrogen can be incorporated into a ring system. A second point for structural modification is the side chain. As already demonstrated, the alpha-methyl can be extended to an alpha-ethyl. Other modifications of the side chain would include incorporation into a variety of ring systems, or a,a-dialkylation. Finally, the nature and location of the ring substituents can be modified. 

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