Conformation requirements

The compound shown is quite unreactive in Diels-Alder reactions Make a space filling model of it in the conformation required for the Diels-Alder reaction to see why... 

This chapter will deal exclusively with three-membered rings containing the hetero atoms O, S and N, and fused to the steroid skeleton. Because of the conformational requirements in steroids, not all of the usual methods of synthesis of three-membered rings are applicable to the fused ring system. For the synthesis of steroids to which an aziridine, oxirane or thiirane is attached either in the side chain or at a ring position but not directly fused to the nucleus, the methods discussed in this chapter, as well as others, are applicable. 

The lithium (or calcium) ammonia system apparently does not have severe conformational requirements, since a 17 -acetoxy-20-ketone reacts to give the... 

In this solvent the reaction is catalyzed by small amounts of trimethyl-amine and especially pyridine (cf. 9). The same effect occurs in the reaction of iV -methylaniline with 2-iV -methylanilino-4,6-dichloro-s-triazine. In benzene solution, the amine hydrochloride is so insoluble that the reaction could be followed by recovery. of the salt. However, this precluded study mider Bitter and Zollinger s conditions of catalysis by strong mineral acids in the sense of Banks (acid-base pre-equilibrium in solution). Instead, a new catalytic effect was revealed when the influence of organic acids was tested. This was assumed to depend on the bifunctional character of these catalysts, which act as both a proton donor and an acceptor in the transition state. In striking agreement with this conclusion, a-pyridone is very reactive and o-nitrophenol is not. Furthermore, since neither y-pyridone nor -nitrophenol are active, the structure of the catalyst must meet the conformational requirements for a cyclic transition state. Probably a concerted process involving structure 10 in the rate-determining step... 

Fig. 23. Space filling model of the Enniatin B—K + complex after the crystal structure 103). Since the carbonyl moieties coordinating the cation are similar for Enniatin B and Valinomycin, the difference in selectivities must arise due to the energetics of the conformations required to achieve coordination of the cation...

Fig. 2.27 The two types of extended /1-peptide strands with conformation requirements around the C(a)-C(/1) bonds. (A) Parallel and antiparallel polar sheets with antiperiplanar conformations around the C(a)-C fl) bond are promoted by unlike-fi -ami-no acids with alkyl side-chains. Antiperiplanar side-chains at C(a) and C(/3) occupy positions approximately perpendicular to the amide planes. (B) Extended strands formed by alternating +)-sc and (-)-sc conformations...

Schiller PW, DiMaio J. Opiate receptor subclasses differ in their conformational requirements. Nature (London) 1982 297 74-76. 

The E2 conformation requires very small dihedral angles between the hydrogen atoms on C-3 and C-4, as well as those on C-4 and C-5, and this is not verified by the values resulting from the corresponding coupling-constants. 

DeJong, A. P., Fesik, S. W., and Makriyannis, A. (1982) Conformational requirements for norepinephrine uptake by phenethylamines in brain synaptosomes. Effects of a-alkyl substitution. J. Med. Chem., 25 1438—1441. 

In another study concerning the conformational requirements of I-cyclopropyl-quinolones and their relationship to DNA gyrase inhibition, the conformation-ally constrained cyclopropane derivative (62), related to ofloxacin was prepared and evaluated in whole cells and for inhibition of DNA gyrase [95] the gem-dimethyl analogue (35), discussed earlier in the context of QSAR studies... 

More recent results have provided additional detail on the conformational requirements for bicyclo[1.1.0]butane formation from conjugated dienes158. Hopf and coworkers have shown that high yields of the isomeric bicyclobutane 78 are obtained from irradiation of... 

The formation of bicyclo[3.1.0]hex-2-enes is a common reaction of cyclic and acyclic cZt-l,3,5-trienes. While it has been frequently depicted as a [n4 + tt2]-cycloaddition and it often exhibits the stereochemistry expected of a concerted [zr4s + rr2a] process109, it is well known that it just as often does not. The stereochemistry, conformational requirements and scope of the reaction have been thoroughly studied by a number of workers, and have been extensively reviewed116,128,170 172. 

Ohfune and coworkers78 used Diels-Alder reactions between 2-trimethylsilyloxy-l,3-butadiene (63) and acrylate esters 64 to synthesize constrained L-glutamates which they intended to use for the determination of the conformational requirements of glutamate receptors. The reactions between 63 and acrylate esters 64a and 64b did not proceed. Changing the ethyl and methyl ester moieties into more electron-deficient ester moieties, however, led to formation of Diels-Alder adducts, the yields being moderate to good. In nearly all cases, the cycloadducts were obtained as single diastereomers, which is indicative of a complete facial selectivity (equation 22, Table 1). Other dienes, e.g. cyclopentadiene and isoprene, also showed a markedly enhanced reactivity toward acrylate 64g in comparison with acrylate 64a. 

In an analysis of stereochemical factors in narcotic analgesics, Portoghese considers that the conformational requirements for most of the 4-phenylpiperidine analgesics appear to be minimal [282]. His argument was based, in part upon (1) the fact that endo and exo isomeric azabicyclo [2,2,1] heptane analogues (LXXXII) of pethidine have similar orders of potency in mice (benzoquinone... 

Lactams are another interesting class of compounds that have been thoroughly explored by Zhang [25]. Methods that are typically used in the synthesis of nonracemic lactams involve C-N bond formation of substrates with preset chiral centers. The Alder-ene carbon-carbon bond forming strategy allows for chiral centers to be set without the use of other pre-existing chirality in the substrate. Initially, enynes with secondary amide tethers were studied but no cyclization was observed. Zhang reasoned that the favored transoid conformation of the secondary amide prevents the necessary conformation required for cyclization (Scheme 8.2). 

Chain flexibility also effects the ability of a polymer to crystallize. Excessive flexibility in a polymer chain as in polysiloxanes and natural rubber leads to an inability of the chains to pack. The chain conformations required for packing cannot be maintained because of the high flexibility of the chains. The flexibility in the cases of the polysiloxanes and natural rubber is due to the bulky Si—O and rxv-olelin groups, respectively. Such polymers remain as almost completely amorphous materials, which, however, show the important property of elastic behavior. 

Electron densities of ortho- and para-positions of biphenyl are higher than that of meta-posltions. Sterically non-controlled isopropylatlon of biphenyl at low temperature occurred predominantly at ortho and para-posltlons to give 2-and 4-IPBP because of the electrophilic nature of the alkylation. However, selective formation of 4-IPBP over HM is controlled by the sterlc restrictions depending on the elliptical pore of the zeolite and on the conformation of the transition state for the formation of products. The molecule 2-IPBP has approximately 0.75 nm of diameter In a twisted bulky conformation with an angle of 64°[8]. The formation of 2-IPBP is prevented over HM because the corresponding transition state with bulky conformation requires more space than is available at the acidic sites of HM. On the other hand, the formation of 4-IPBP proceeds unhindered because of its smaller transition state. The formation of 3-IPBP Is also less hindered because of flexible conformations at transition states In HM pore. 

Nevertheless, the inactivated vaccine approach suffers from several shortcomings. The process could inactivate not only the organism but also destroy the antigen conformation required to elicit protective immunity. Incomplete inactivation (e.g., virion aggregation resulting in poor exposure to the inactivating agent) could result in disease transmission or severe complica-... 

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