A conformationally restricted

In order to give useful information about an enzyme, a conformationally restricted active-site-directed analog inhibitor need not bind to the enzyme irreversibly. In a study of the enzyme fructose 1,6-diphosphatase from rabbit liver, Benkovic et al, have investigated the question of the reactive form of the fructose 1,6-diphosphate in the enzymatic process (104,105). Three likely forms are shown in structures 50, 51 and 52. 

To round out this group of drugs in which the piperazine ring appears to serve primarily as a basic spacer unit, or a conformationally restricted ethylene-diamine unit, reaction of N-phenylpiperazine (135) with acrylonitrile produces nitrile 136. Conversion... 

We examined the effect of restricted conformation on the activation entropy by kinetic studies at various temperatures [34]. Three kinds of substrates were subjected to the reaction phenylmalonic acid as the standard compound, ortho-chlorophenylmalonic acid as a substrate with an electron-withdrawing group, and indane-l,l-dicarboxylic acid as a conformationally restricted compound. The initial rates of the enzymatic decarboxylation reaction of three compounds were measured at several substrate concentrations at 15 °C, 25 °C, and 35 °C. The kcat and values at each temperature were obtained by a Lineweaver-Burk plot,... 

For determination of its configuration via a conformationally restricted cyclic derivative, A -allylamino alcohol derivative 475 was treated with tris(triphenylphosphine)rhodium(l) chloride to afford a 19 1 mixture of the C-2-epimeric tetrahydro-l,3-oxazines 476 and 477 by intramolecular trapping of the intermediate iminium species, in equilibrium with the enamine generated in the isomerization of the allyl double bond (Equation 52) <1997CC565>. 

Dihydromuscimol (49) is a conformationally restricted analogue of the physiologically important neurotransmitter y-aminobutyric acid (GABA) and has been prepared using the cycloaddition of dibromoformaldoxime to A-Boc-allylamine followed by N-deprotection with sodium hydroxide (Scheme 6.52) (278). The individual enantiomers of dihydromuscimol were obtained by reaction of the bromonitrile oxide with (5)-( + )-l,2-0-isopropylidene-3-butene-l,2-diol, followed by separation of the diastereoisomeric mixture (erythro/threo 76 24), hydrolysis of respective isomers, and transformation of the glycol moiety into an amino group (279). 

White, W. F., Zhao, D. (3R,4S)-3-[4-(4-Fluorophenyl)-4-hydroxypiperidin-1-yl]chroman-4,7-diol a conformationally restricted analoque of the NR2B subtype-selective NMD A antagonist (1S,2S)-1-(4-hydroxyphenol)-2-(4-hydroxy-4-phenylpiperidino)-1-propanol, J. Med. Chem. 1998, 41, 1172-1184. 

Lehn, J. M., Sauvage, J. P., Simon, J., etal, Synthesis and metal-complexes of a conformationally restricted quaterpyridine -crystal-structure of its dimeric dinuclear Cu (I) complex, [Cu2(pqp)2]2+. Nouv. J. Chim. - New J. Chem. 1983, 7, 413-420. 

Figure 4.3 Clonidine and its m,p-dichloro analogue. It is believed that the bulky chloro groups impose a conformation restriction on clonidine, which probably accounts for its greater activity...

Nitrosation at the 5-position of 3-methoxy-4,5,6,7-tetrahydroisoxazolo[4,5-c]pyridine (237) has been used as a method to block this basic nitrogen in the synthesis of compound (242) (Scheme 23), a conformationally restricted 7V-methyl-(/ )-aspartic acid analogue, for evaluation as a potential excitor of neurotransmitters in the mammalian central nervous system <82Mi 708-02, 86ACS(B)92>. Lithiation of the derivative (238) with n-butyllithium regiospecifically at the 4-position followed by C-alkylation with the addition of methyl chloroformate gave the 4-methoxycarbonyl derivative (239), albeit in a low 16% yield. The remainder of the synthetic sequence involves a stepwise deprotection sequence (239)-(242). 

Mullen G, Napier J, Balestra M, DeCory T, Hale G, et al. 2000. (-) -Spiro [ 1 -azabicyclo [2.2.2] octane-3,5 -oxazolidin-2 -one], a conformationally restricted analogue of acetylcholine, is a highly selective full agonist at the alpha-7 nicotinic acetylcholine receptor. J Med Chem 43 4045-4050. 

Barboni, L. Lambertucci, C. Ballini, R. Appendino, G. Bombardelli, E. Synthesis of a conformationally restricted analogue of paclitaxel. Tetrahedron Lett., 1998, 39 7177-7180. 

Photoprocesses in biliverdin dimethyl ester in ethanol have been studied by laser-induced optoacoustic spectroscopy." The picosecond kinetics of excited-state relaxation of this ester have also been reported." " Isophorcarubin is a conformationally restricted and highly fluorescent bilirubin." " The phototherapy for neonatal jaundice has stimulated investigations of configurational isomers of bilirubin" and of stereospecific and regioselective photoisomerization of bilirubin." ... 

Inhibition properties and the syntheses of a conformationally restricted probe for the mutase-catalysed UDP-galactose/furanose interconversion (237a) and of... 

Ichikawa, S, Shuto, S, Matsuda, A, The first synthesis of herbicidin B. Stereoselective construction of the tricyclic undecose moiety by a conformational restriction strategy using steric repulsion between adjacent bulky silyl protecting groups on a pyranose ring, J. Am. Chem. Soc., 121, 10270-10280, 1999. 

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