Side Chain-Modified

Photochemical ting opening of 7-dehydrocholesterol derivatives which have ting A or the side chain modified (142,143). 

The Michael addidon of nitto compounds is a useful method for the preparadon of various naniral products The Michael kldidon of nittoalkanes to dehydroalanines gives ynitto-ct-amino acids, which provides a convenient synthesis of side-chain modified ct-amino acids fEq 4 114 " Transformadons of Y-nitto-ct-amino acid derivadves into ct-amino adds occur by... 

A variety of side-chain modified analogs of MDMA and MBDB have begun to be examined. Very early studies were of the a,a-dimethyl analog, 3,4-methylenedioxyphentermine (figure 8a) and its N-methyl derivative (figure 10). This latter compound proved to lack MDMA-like activity (Shulgin, unpublished). Interestingly, this compound also lacked the ability to stimulate the release of [ H] serotonin from prelabeled rat brain synaptosomes (Nichols et al. 1982). 

Tables 6.8-6.11 illustrate the wide range of C3 side-chain modified A -THC analogues that have been reported in the literature, together with associated in vitro and in vivo data. The affinity of classical cannabinoid analogues for the CBi receptor has been shown to correlate with depression of spontaneous activity and the production of antinociception, hypothermia and catalepsy in mice, and with psychomimetic activity in humans [93]. However, in some cases, there were unexplained differences between the observed trends in binding affinity and the trends in activity in mouse behavioural models. This may point to differences in efficacy among full agonists, partial agonists and antagonists/inverse agonists, or may reflect differences in in vivo metabolism or blood-brain barrier penetration or a combination of these factors.

Cannabidiol has low affinity for CBi and CB2 receptors and is not psychoactive, but has nevertheless shown a number of pharmacological activities of its own including anti-inflammatory and neuroprotective effects. Some side chain-modified cannabidiol derivatives have also been evaluated for can-nabinoid receptor affinity and these are shown in Table 6.15. 

Preferred Amino Acid Side Chain Modified Modifying Agent... 

Scheme 9. Synthesis of epothilone E and side-chain modified epothilones via RCM and Stille coupling, (a) 0.1 equiv of RuCl2(=CHPh)(PCy3)2 (3), CH2C12,0.004 M, 25°C, 20 h, 65% (41a 41b=1.8 l) (b) HF Py, THF,43 (84%) 44 (85%) (c) R13Sn(Aro), Pd(PPh3)4 or Pd(MeCN)2Cl2, 55-90% (d) H202, CH3CN, KHC03, 65%. Aro=aromatic (Nicolaou et al.) [20]...

The acylated Meldrum s acid approach has also been used by Shaefer et al. [57] and recently by Reverchon and coworkers [53] to prepare novel synthetic AT-(3-oxoacyl)-L-HSL derivatives with their acyl side-chain modified by introducing unsaturation, ramified alkyl, cycloalkyl 18 or aryl 19 substituents at the C-4 position. 

Table 1 Posttranslational modifications by amino acid side chain modified ...

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. 

Scheme 2 Side-Chain Modified Amino Acids...

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. 

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