Stereochemical course

H -ATPase catalyzes terminal transphosphorylation in ATP synthesis. The presence of phosphorylated intermediate in this reaction was suggested by kinetic analysis [103-105], and isolation of an acylphosphate phosphoenzyme in ion transporting ATPases, including Ca -ATPase [159], Na, K -ATPase [160] and plasma mem- 

The true substrate of FqFj is MgATP, rather than the free nucleotide. There is a strict stereochemical requirement for the structure of metal-nucleotide complexes in the phosphorylation reaction [161]. In the case of myosin ATPase, for example, the Sp diastereoisomer (A in Fig. 5.9) of ATP)8S is more rapidly hydrolyzed than its Rp diastereoisomer (B in Fig. 5.9) with Mg with an Sp/Rp ratio of 3000, while with 

Cd this ratio is only 0.2 [166]. On the other hand, the Rp diastereoisomer of ATP]8S is preferred by hexokinase when Mg is the cation (Sp/Rp ratio 0.002), and the ratio is reversed with Cd (Sp/Rp ratio, 30) [167]. As shown in Fig. 5.9, Mg prefers the O atom and Cd prefers the S atom as a ligand. Thus, it is reasonable that an enzyme should prefer only one geometrical arrangement. TF, is several times more active than EFj [88] and MFj [87] when Cd is used as the divalent cation. Therefore, the cation-dependent diastereoisomer preference of TF, was determined [164]. Mg(Sp)-ATP SS and Cd(Rp)-ATP 8S, which have the A-configuration, were better substrates than Mg(Rp)-ATP]8S and Cd(Sp)-ATP]8S, both of which have the A-chelate configuration (Fig. 5.9). The Sp/Rp ratios with Mg and Cd were 575 and 0.5, respectively. Both diastereoisomers of ATPaS were substrates for TF, and no metal-dependent diastereomeric selectivity was observed. These results suggest that TF, uses the A, ]8, y-bidentate nucleotide chelate as substrate [164]. This kind of experiment on other F, s was disturbed by the presence of tightly bound Mg and nucleotides. 

Since the Mg exchanges oxygen ligands such as ATP very rapidly, Cr , which forms a stable nucleotide chelate, was used to analyze the transition state on F, [169]. Both CrATP and CrADP interact with F, very much like the corresponding Mg nucleotide chelates. Incubation of F, with monodentate CrADP and P, resulted in the formation of Fj-P,CrADP, from which P,CrADP was isolated. Incubation of Fj with bidentate CrATP also resulted in the same product [169]. This suggests that the synthesis and hydrolysis of ATP-metal chelate takes place via the same transition state on F,. The 1 1 1 ADP-Mg-TF, complex [170] forms ATP-Mg-TF, P, solution. 

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When propene is polymerized under free radical conditions the polypropylene that results IS atactic Catalysts of the Ziegler-Natta type however permit the preparation of either isotactic or syndiotactic polypropylene We see here an example of how proper choice of experimental conditions can affect the stereochemical course of a chemical reaction to the extent that entirely new materials with unique properties result... 

The study of the stereochemical course of organic reactions often leads to detailed insight into reaction mechanisms. Mechanistic postulates ftequently make distinctive predictions about the stereochemical outcome of the reaction. Throughout the chapters dealing with specific types of reactions, consideration will be given to the stereochemistry of a reaction and its relationship to the reaction mechanism. As an example, the bromination of alkenes can be cited. A very simple mechanism for bromination is given below ... 

Studies of the stereochemical course of rmcleophilic substitution reactions are a powerful tool for investigation of the mechanisms of these reactions. Bimolecular direct displacement reactions by the limSj.j2 meohanism are expected to result in 100% inversion of configuration. The stereochemical outcome of the lirnSj l ionization mechanism is less predictable because it depends on whether reaction occurs via one of the ion-pair intermediates or through a completely dissociated ion. Borderline mechanisms may also show variable stereochemistry, depending upon the lifetime of the intermediates and the extent of internal return. It is important to dissect the overall stereochemical outcome into the various steps of such reactions. 

Table 5.16 Stereochemical Course of Nucleophilic Substitution Reactions...

In aqueous dioxane, the endo-anti isomer gave a product mixture consistent of alcohol N and the corresponding ester (derived from capture of the leaving group p-nitrobenzoate). The other isomers gave much more complex product mixtures which were not completely characterized. Explain the trend in rates and discuss the structural reason for the stereochemical course of the reaction in the case of the endo-anti isomer. 

The fundamental mechanistic concept by which the stereochemical course of the aldol addition under conditions of kinetic control has been analyzed involves a cyclic transition state in which both the carbonyl and enolate oxygens are coordinated to a Lewis... 

These are suprafacial sigmatropic shifts of order [1,5] and should occur with retention of configuration at the migrating carbon. This stereochemical course has been established for the 1,5-alkyl shift that converts 16 to 17. The product which is isolated, 18, results from a subsequent 1,5-hydrogen shift, but this does not alter the stereochemistry at the migrating... 

Thus, the transition state depicted on p. 777 for the concerted reaction correctly predicts the stereochemical course of the di-7c-methane rearrangement. 

Since the stereochemical course of a catalytic hydrogenation is dependent on several factors, " an understanding of the mechanism of the reaction can help in the selection of optimal reaction conditions more reliably than mere copying of a published recipe . In the first section the factors which can influence the product stereochemistry will be discussed from a mechanistic viewpoint. In subsequent sections the hydrogenation of various functional groups in the steroid ring system will be considered. In these sections both mechanistic and empirical correlations will be utilized with the primary emphasis being placed on selective and stereospecific reactions. 

Stereochemical course of the reaction. This kind of information was critical in the elucidation of the SnI and Sn2 pathways for nucleophilic substitution at saturated carbon. 

The stereochemical course of reduction of imonium salts by Grignard reagents was found to depend on the structure of the reagent 714). Hydro-boration of enamines and oxidation with hydrogen peroxide led to amino-alcohols (7/5). While aluminum hydrogen dichloride reacted with enamines to yield mostly saturated amines and some olefins on hydrolysis, aluminum hydride gave predominantly the unsaturated products 716). 

The stereochemical course of the Beckmann rearrangement often allows for the prediction of the reaction product to be obtained in general the substituent R anti to either the hydroxy or the leaving group will migrate ... 

The stereochemical outcome of the reaction is determined by the geometry of the transition state for the Claisen rearrangement a chairlike conformation is preferred,and it proceeds strictly by an intramolecular pathway. It is therefore possible to predict the stereochemical course of the reaction, and thus the configuration of the stereogenic centers to be generated. This potential can be used for the planning of stereoselective syntheses e.g the synthesis of natural products. 

Evidence for that stereochemical course comes from the rearrangement of meso-3,4-dimethylhexa-1,5-diene 4, which yields the E.Z-configured diene 5 almost quantitatively. With a transition state of boatlike geometry, a Z,Z- or E,E-configured product would be formed." ... 

The addition usually takes place from the sterically less hindered side of the alkene. The stereochemical course of the addition can be controlled by suitably positioned oxygen center that can coordinate to the organozinc reagent. For example the reaction with 4-hydroxycyclopentene 6 as substrate exclusively yields the c -3-hydroxybicyclo [3.1.0] hexane 7 ... 

It would be reasonable to expect that the decomposition of the N,N-dimethylimino ester chlorides proceeds via a bimolecular mechanism already demonstrated for the thermal decomposition of simple imino ester salts (79). In the carbohydrate series, where an isolated secondary hydroxyl group is involved, such a process would result in chlorodeoxy sugar derivatives with overall inversion of configuration, provided that the approach of the chloride ion is not sterically hindered. Further experiments are in progress in this laboratory utilizing additional model substance to establish the scope and stereochemical course of the chlorination reaction. 

A sequence of straightforward functional group interconversions leads from 17 back to compound 20 via 18 and 19. In the synthetic direction, a base-induced intramolecular Michael addition reaction could create a new six-membered ring and two stereogenic centers. The transformation of intermediate 20 to 19 would likely be stereoselective substrate structural features inherent in 20 should control the stereochemical course of the intramolecular Michael addition reaction. Retrosynthetic disassembly of 20 by cleavage of the indicated bond provides precursors 21 and 22. In the forward sense, acylation of the nitrogen atom in 22 with the acid chloride 21 could afford amide 20. 

Schemes 3-7 describe the synthesis of cyanobromide 6, the A-D sector of vitamin Bi2. The synthesis commences with an alkylation of the magnesium salt of methoxydimethylindole 28 to give intermediate 29 (see Scheme 3a). The stereocenter created in this step plays a central role in directing the stereochemical course of the next reaction. Thus, exposure of 29 to methanol in the presence of BF3 and HgO results in the formation of tricyclic ketone 22 presumably through the intermediacy of the derived methyl enol ether 30. It is instructive to point out that the five-membered nitrogen-containing ring in 22, with its two adjacent methyl-bearing stereocenters, is destined to become ring A of vitamin Bi2. A classical resolution of racemic 22 with a-phenylethylisocyanate (31) furnishes tricyclic ketone 22 in enantiomerically pure form via diaster-eomer 32.

The issue of stereochemistry, on the other hand, is more ambiguous. A priori, an aldol condensation between compounds 3 and 4 could proceed with little or no selectivity for a particular aldol dia-stereoisomer. For the desired C-7 epimer (compound 2) to be produced preferentially, the crucial aldol condensation between compounds 3 and 4 would have to exhibit Cram-Felkin-Anh selectivity22 23 (see 3 + 4 - 2, Scheme 9). In light of observations made during the course of Kishi s lasalocid A synthesis,12 there was good reason to believe that the preferred stereochemical course for the projected aldol reaction between intermediates 3 and 4 would be consistent with a Cram-Felkin-Anh model. Thus, on the basis of the lasalocid A precedent, it was anticipated that compound 2 would emerge as the major product from an aldol coupling of intermediates 3 and 4. 

In this beautiful synthesis of periplanone B, Still demonstrated a classical aspect and use of total synthesis - the unambiguous establishment of the structure of a natural product. More impressively, he demonstrated the usefulness of the anionic oxy-Cope rearrangement in the construction of ten-membered rings and the feasibility of exploiting conformational preferences of these medium-sized rings to direct the stereochemical course of chemical reactions on such templates. 

In his original paper,2 Cram disclosed an alternative model that rationalizes the preferred stereochemical course of nucleophilic additions to chiral carbonyl compounds containing an a heteroatom that is capable of forming a complex with the organometallic reagent. This model, known as the Cram cyclic or Cram chelate model, has been extensively studied by Cram9 and by others,410... 

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