Conformational flipping

In the absence of steric factors e.g. 5 ), the attack is antiparallel (A) (to the adjacent axial bond) and gives the axially substituted chair form (12). In the presence of steric hindrance to attack in the preferred fashion, approach is parallel (P), from the opposite side, and the true kinetic product is the axially substituted boat form (13). This normally undergoes an immediate conformational flip to the equatorial chair form (14) which is isolated as the kinetic product. The effect of such factors is exemplified in the behavior of 3-ketones. Thus, kinetically controlled bromination of 5a-cholestan-3-one (enol acetate) yields the 2a-epimer, (15), which is also the stable form. The presence of a 5a-substituent counteracts the steric effect of the 10-methyl group and results in the formation of the unstable 2l5-(axial)halo ketone... 

Kadirvel M, Arsic B, Freeman S, Bichenkova EV (2008) Exciplex and excimer molecular probes detection of conformational flip in a myo-inositol chair. Org Biomol Chem... 

Recently, two research groups have independently synthesized the conforma-tionally constrained neomycin derivatives, 74, with the 2 -NH2 group linked to the C-5" (Scheme 4.13). The information from X-ray crystallography has revealed a drastic conformational flipping of the 2-deoxystreptamine component between the binding sites of rRNA and ANT(40. ° Thus, it is proposed that an intramolecular link may obstruct the needed conformational change for ANT(4 )-catalyzed modification. Compound 74 shows lower activity against... 

Table 1. Coalescence Temperatures (Tc), Free Energies of Activation for the Conformational Flipping Process (AC ), and NMR Operating Frequencies for Measurement of Compounds 85, 89, 91-94. ...

Conformational flips can be used to assist catalytic activity. Concerted flips could be used to relay information (e.g., in cytochrome c). Here there are one tyrosine and one phenylalanine that seem to have concerted onset of motion. Such changes begin to look like second-order phase transitions and are obviously important in membranes. 

Cooke 17) has recently reported the synthesis of 18 in order to compare the steric interactions and rates of conformational flipping with other systems (2, 3, and 9). The synthesis of 18 has been accomplished in two ways, both involving the intermediate 2-thiapyridinophane one utilizes the Ramberg-Backlund rearrangement while the other depends on the Stevens rearrangement, as depicted in Scheme III. 

Pyridinoparacyclophane (30)23) exhibits a temperature-dependent H NMR spectrum in which 30 is certainly undergoing conformational flipping. The AG value for 30 is 10.7 kcal/mole and is significantly smaller than the value of 20.6 kcal/mole for the carbocyclic analog 31. 

In biological structures, the conformational flip-flop disorder will occur in the carbohydrates, the cyclodextrins, in water, or generally, in all systems where hydroxyl groups are involved. 

Fig. 3.9 Diagrams of molecular relaxation mechanisms (a) conformational flip of chlorohexane, (b) crankshaft rotation in polyethylene.

The racemate of 140 has been partially separated on a TAP A (772)-impregnated silicagel column The rate of racemization (k = 1.9 x 10" min ) and the half-life (tiy2 = 38 min at 210 °C) are of the same order as those of hexahelicene (t./j = 48 min at 205 °C). This means that the conformational flipping of the one helical part of the molecule is not strongly hindered by the other. An intermediate of this conformational process therefore should be the symmetrical meso form. 

IConresolvable dl mixture, each enantiomer is converted to its mirror image by a conformational flip. 

Conformation of Bound Inhibitor. Another area under investigation focuses on the conformations) of the substrate and an inhibitor (MTX) bound to DHFR. The form of the DHFR/MTX complex is known from the crystallographic studies of Kraut et al. (8-10). However, the orientation of the bound pterin ring in the reactive DHFR/DHF is known to differ dramatically from the MTX crystal structure (20). Basically, these differences arise because there are two possible orientations of the pterin ring in the active site one is flipped by 180° with respect to the other. Isotope labelling experiments on THF show that the reactive DHF must be bound in the conformation flipped from that observed by x-ray for MTX. In order to understand these differences, we ran simulation studies on altered forms of bound MTX and DHF to investigate the structural and energetic properties of these systems. 

An argument similar to that for the hydrolysis of D-gluconolactone leads us to 59 as the final product, wherein the label O18 has been incorporated. The transformation 57 —> 60 is not allowed for the lack of support by the requisite two stereoelectronic effects. Conformational ring flip from 57 to 61 is energy requiring. It may therefore be claimed not to compete with the fast cleavage of 57 to 58 because the latter is supported by two stereoelectronic effects. Let us see the turn of events assuming that the said conformational flip does compete and 61 is indeed formed. 

The conformational flip is in part influenced by the presence of bulky internal (C2-) substituents. A case in point is the exclusive formation of 215sf from a coupling between the diphenolic cuppedophane 186 and p-xylylene dibromide [Eq. (21)]. The presence of a bromine atom at the internal position is believed to be responsible for the flip of the phenolic rings, leading to the sole formation of 215sf. It has been previously observed in solid state structures of cuppedophanes [20] that a conformational flip of wall component rings occurs if the m-terphenyl unit bears internal bulky substituents (see Fig. 1). 

The formation of self-filled phanes in coupling reactions between diphenolic cuppedophanes and capping units (Scheme 31) could also be attributed to the nature and reactivity of the capping unit. For example, with p-xylylene dibromide as the capping unit, the rate of the second alkylation of the phenol was apparently faster than the rate of conformational flip, thus leading to the predominance of 208v. However that was not the case when the capping unit... 

Of interest in this connection is the fact that a /-l,2,5,6-tetracyanotricy-clo[4.2.0.0 ]octane gives exclusively the tcimcyano-cis trans-COD in the solid state with log = 15.6 - 34900/2.This reaction is about 4000 times slower than that of ring opening of l,4-dicyanobicyclo[2.2.0]hexane suggesting that crystal packing force retards the further conformational flip of a chair-like biradical to cleave to the COD (Scheme 9.93). ... 

Figure 11.5 A pH-triggered conformational flip in amphiphilic trans-3,4 bis(acyloxy)-hbenzylpiperidines (flipids) increases the separation of hydrocarbon chains.

Samoshin, V. V. (2014). Fliposomes stimuli-triggered conformational flip of novel amphiphiles causes an instant cargo release from liposomes, Biomolecular Concepts, 5,131-141. 

NMR studies have revealed that two dynamic processes occur in cyclooctate-traenes. One is a conformational flip ... 

Proton a is 5.8 ppm upheld of b, indicating the existence of an aromatic ring current. The ir-system also apparently contributes to imposing a high barrier to conformational flip of the saturated carbon ... 

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