Stereochemical requirement

Given the following partial structure add a substituent X to C 1 so that It satisfies the indicated stereochemical requirement You may find it help ful to build a molecular model for reference... 

The reaction is reversible and its stereochemical requirements are so pronounced that neither the cis isomer of fumaric acid (maleic acid) nor the R enantiomer of malic acid can serve as a substrate for the fumarase catalyzed hydration-dehydration equilibrium... 

Efforts have been made to correlate electronic stmcture and biological activity in the tetracycline series (60,61). In both cases, the predicted activities are of the same order as observed in vitro with some exceptions. The most serious drawback to these calculations is the lack of carryover to in vivo antibacterial activity. Attempts have also been made (62) to correlate partition coefficients and antibacterial activity. The stereochemical requirements are somewhat better defined. Thus 4-epitetracycline and 5a-epitetracycline [65517-29-5] C22H24N20g, are inactive (63). The 6-epi compound [19369-52-9] is about one-half as active as the 6a (or natural) configuration. 

A classic diagnostic use of such stereochemical requirements, due to Ruzicka, is the ring contraction induced in natural products containing the 4,4-dimethyl-5a-3 -ol system (94). The epimeric, axial 3a-alcohols (95) dehydrate without ring contraction. Barton suggested that it is necessary for the four reacting centers (hydroxyl, C-3, C-4, C-5) to be coplanar for ring contraction to occur, and this is only the case with the 3)5-alcohol. 

As with other high coordination numbers, there seems to be little difference in energy between these structures. Factors such as the number of counter ions and the stereochemical requirements of chelating ligands are probably decisive and a priori arguments are unreliable in predicting... 

The thermolysis of xanthates derived from primary alcohols yields one olefin only. With xanthates from secondary alcohols (acyclic or alicyclic) regioisomeric products as well as fi/Z-isomers may be obtained see below. While acyclic substrates may give rise to a mixture of olefins, the formation of products from alicyclic substrates often is determined by the stereochemical requirements the /3-hydrogen and the xanthate moiety must be syn to each other in order to eliminate via a cyclic transition state. 

Restrictions for the substrates of the transketolase-catalyzed reaction only arise from the stereochemical requirements of the enzyme. The acceptor aldehyde must be formaldehyde9,20, glycolaldehydel6,17 or a (R)-2-hydroxyaldehyde10,17. The donor ketose must exhibit a (3(7,4 R) configuration10. The enzyme selectively adds the hydroxyacetyl moiety to the Re-face of the acceptor aldehyde leading to a 3(7 configuration of the products. 

The main utility of Peterson olefination lies in the contrasting stereochemical requirements (6) for elimination, use of base requiring a syn conformation whereas acid conditions demand an anti conformation, with complementary geometrical results ... 

The transition state of concerted Diels-Alder reactions has stringent regio- and stereochemical requirements and can assume settled configurations if the reaction is carried out in a molecular cavity. Cyclodextrins, porphyrin derivatives and cyclophanes are the supramolecular systems that have been most investigated. 

NeuA, has broad substrate specificity for aldoses while pyruvate was found to be irreplaceable. As a notable distinction, KdoA was also active on smaller acceptors such as glyceraldehyde. Preparative applications, for example, for the synthesis of KDO (enf-6) and its homologs or analogs (16)/(17), suffer from an unfavorable equilibrium constant of 13 in direction of synthesis [34]. The stereochemical course of aldol additions generally seems to adhere to a re-face attack on the aldehyde carbonyl, which is complementary to the stereoselectivity of NeuA. On the basis of the results published so far, it may be concluded that a (31 )-configuration is necessary (but not sufficient), and that stereochemical requirements at C-2 are less stringent [71]. 

Of added interest in this study was the finding that the enantiomeric ratios of a-terpineol also differ widely among populations. In southern populations and the population from the northwestern tip of the island, the amount of (+)-a-terpineol was shown to range from 92.3 to 97.0%, while this enantiomer made up 85.6% in the upper-middle population, but only 66.0% in the population from the southeastern tip of the island. It would be of interest to see if the enzymes responsible for the biosynthesis of a-terpineol have different stereochemical requirements in these populations, or whether some isomerization has occurred in the formation, preparation, or analyses of these oil samples. 

Like amine oxide elimination, selenoxide eliminations normally favor formation of the E-isomer in acyclic structures. In cyclic systems the stereochemical requirements of the cyclic TS govern the product composition. Section B of Scheme 6.21 gives some examples of selenoxide eliminations. 

Schiller PW, Nguyen TM-D, Weltrowska G, Wilkes BC, Marsden BJ, Lemieux C, Chung NN. Differential stereochemical requirements of p vs 6... 

Thus solvolysis of (+)C6HsCHMeCl, which can form a stabilised benzyl type carbocation (cf. p. 84), leads to 98% racemisation while (+)C6H13CHMeCl, where no comparable stabilisation can occur, leads to only 34% racemisation. Solvolysis of ( + )C6H5CHMeCl in 80 % acetone/20 % water leads to 98 % racemisation (above), but in the more nucleophilic water alone to only 80% racemisation. The same general considerations apply to nucleophilic displacement reactions by Nu as to solvolysis, except that R may persist a little further along the sequence because part at least of the solvent envelope has to be stripped away before Nu can get at R . It is important to notice that racemisation is clearly very much less of a stereochemical requirement for S l reactions than inversion was for SN2. 

Ketley, J. N., Schellenberg, K. A. Substrate stereochemical requirements in the reductive inactivation of uridine diphosphate galactose 4-epimerase by sugar and 5 -uridine monophosphate. Biochemistry 12, 315—320 (1973). 

Fig. 7.5. General formula summarizing the structural and stereochemical requirements, which an ester should meet to fit into the active site of pig liver esterase. A nucleophilic attack by the serine OH group seemingly occurs from this side B no or only small substituents allowed here C groups of small to medium size allowed in this area D space allowed in these areas for carbon chains, with polar substituents (e.g., another ester group) preferred in the upper part ...

The second step of the sphcing reaction is catalyzed within the same catalytic site as the first step [48, 140, 141]. Moreover, in the presence of Mg ions, both the reverse reaction of the first step and the forward reaction of the second step were inhibited with the l pS substrate [note that the pro-Rp oxygen at these steps corresponds to the pro-Sp oxygen in the forward reaction of the first step]. These observations indicate that the stereochemical requirements are the same in both reactions [123, 132, 142, 143]. Therefore, the mechanism of the second step is considered to be analogous to the mechanism of the first step [48]. 

---