Sidechains

Fig. XV-16. A schematic drawing of the arrangement of polyglutamates having alkyl side chains in an LB film. The circles represent the rodlike polyglutamate backbone oriented perpendicular to the page the wiggly lines are the alkyl sidechains. (From Ref. 182.)...

Conformational free energy simulations are being widely used in modeling of complex molecular systems [1]. Recent examples of applications include study of torsions in n-butane [2] and peptide sidechains [3, 4], as well as aggregation of methane [5] and a helix bundle protein in water [6]. Calculating free energy differences between molecular states is valuable because they are observable thermodynamic quantities, related to equilibrium constants and... 

Rhamsan Gum. Rhamsan gum, produced y lcaligenes strain (ATCC 31961) (91), has the same backbone as geUan and welan gums, but it carries a disaccharide sidechain (92). 

Penicillins are also degraded by aqueous acids via initial reaction of the sidechain carbonyl group with the P-lactam. PeniciEenic acids (33) are obtained when hydrolysis is carried out at pH 4, penillic acids (34) at pH 2. 

The widespread use of cinnamic derivatives has led to the pursuit of reUable methods for thek dkect synthesis. Commercial processes have focused on condensation reactions between ben2aldehyde and a number of active methylene compounds for assembly of the requisite carbon skeleton. The presence of a disubstituted carbon—carbon double bond in the sidechain of these chemicals also gives rise to the existence of two distinct stereoisomers, the cis or (Z)- and trans or (E)- isomers ... 

This is a term introduced by Gokel and co-workers only very recently. The compounds included in this class are those which have single macrorings like crowns but additional pendant donor groups which make them similar in some respects to crytands. The presumption from which the name derives is that a complexed cation will be bound by both the macroring and the sidechain in much the same fashion as a lasso binds an animal. The compounds are named as simple crown derivatives and are illustrated as 16 a 17 below. 

The 20 natural amino acids differ from each other by the nature of their sidechains. Differences involve overall size, hydrophobic or hydrophilic character and, perhaps most importantly, ionization state. While the sidechains are normally written in terms of neutral structures, some may also exist in either protonated or deprotonated forms depending on pH. 

Quazepam (88) has a highly fluorinated sidechain so as to make this tranquilizer resistant to dealkylation. It also incorporates a lipid-solubilizing 2-thione moiety. The synthesis begins with bi aryl ketone derivative by ] -al kylation with 2,2,2-trifluoroethyltriclate to give 86. 

Rezeptor, m. receptor, receiver. Rezeptorenseitenkette, /. receptor sidechain. Rezeptur, /. dispensing (of medicines) recipe ... 

By the use of nuclear magnetic double (and triple) resonance, the configuration (34) of pseudo-talose was established, confirming chemical evidence, and the sidechain-equatorial conformation (38) was also... 

Palladium-mediated catalysis has only been exploited relatively recently in the synthesis of substituted PPV derivatives. The use of aryl dibromides as monomers is particularly useful as it allows the synthesis of PPVs substituted with alkyl rather than alkoxy sidechains. The Suzuki [53, 54], Heck [55], and Stille [56] reactions have been used in the synthesis of new PPV derivatives, but attaining high molecular weight PPV derivatives by these methodologies has proved problematic. A phenyl-subslilutcd PPV material PPPV 31 was synthesized by a Suzuki coupling (Scheme 1-10) of dibromoethene and fo/.v-boronic acid 30. Its absorption (2ni ix=385 nm) and emission (2max=475 nm) maxima were strongly... 

Fig. 1.6 A comparison of the CD spectra of oligopeptoids with achiral Npm side chains (1) and with a-chiral, aromatic sidechains of S and R chirality (2 and 6, respectively). Sample concentration was 60 j,M in acetonitrile. Spectra were acquired at room temperature. Npm = (N-[l-phenylmethyljglycine) Nspe= (S)-N-(l -phenylethyl)glycine Nrpe= (R)-N-(l -phenylethyl)glycine...

Table 14 Maximum conductivity of the polyphosphazenes with branched ethyleneoxy sidechains/hthium triflate systems at 25 °C...

Figure 1. Most cx)mmon (consensus) sequences of the two types of sea anemone toxins. Bold letters represent residues which both toxin types have in common. Letters above each sequence are nonconservative substitutions, while letters below each sequence are conservative substitutions. A nonconservative substitution was defined as one in which (a) electronic charge changed, (b) a hydrogen-bonding group was introduced or removed, (c) the molecular size of the sidechain was changed by at least 50%, or (d) the secondary structure propensity was changed drastically from b to h or vice versa (Ref.

Sidechain conservatism may be split up into at least two kinds 1) substitutions which conserve sidechain bonding forces - providing similar electrostatic, hydrophilic, or hydrogen bonding interactions, and 2) substitutions conserving secondary structure propensity. For instance, substitution of glutamic acid with aspartic acid conserves charge, but this could have a considerable effect upon the secondary structure propensity of the peptide. 

Some chemical modification studies on the sea anemone toxins have unfortunately been less than rigorous in analyzing the reaction products. Consequently, results from many of these studies can only provide suggestions, rather than firm conclusions, regarding the importance of particular sidechains. Many such studies also have failed to determine if the secondary and tertiary structures of the toxin products were affected by chemical modification. 

Investigation of a related indole template, however, yielded potent compounds, as exemplified by the sulphonamide derivative (33). Activity was improved further by introducing steric constraints to the sidechain and introduction of a 7-methyl substituent on the indole ring, leading to compound (34) [82]. Derivatives generally possessed only moderate pharmacokinetic properties however (clearance 25-45 ml/min/kg in dog), which was attributed to metabolic vulnerability of the indole (C2-C3) double bond. Attempts to block metabolism by C2, C3 di-methyl substitution resulted in the loss of oxytocin activity. 

This process, or simple variants of it, is used to prepare many drugs. For example, one method for the synthesis of fenoterol (6), a bronchodilator, starts with sidechain bromination of m-diacetoxy-... 

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