Stereochemistry topological

Simulation and Evaluation of Chemical Synthesis (SECS) was developed by Wipke and uses heuristic methods similar to LHASA but puts special emphasis on stereochemistry, topology, and energy minimization [112]. 

Macromolecular synthesis involves the design of synthetic methodology for the formation of macromolecular architecture, including controlled molecular weight and molecular weight distribution, stereochemistry, topology (linear, branched, and cross-linked), block and graft copolymers, and... 

A proton can be (numerically) represented by a series of topological and physicochemical descriptors, which account for the influence of the neighborhood on its chemical shift. Fast empirical procedures for the calculation of physicochemical descriptors are now easily accessible [45. Geometric descriptors were added in the case of some rigid substructures, as well as for rr-systems, to account for stereochemistry and 3D effects. 

Up to this point, we have emphasized the stereochemical properties of molecules as objects, without concern for processes which affect the molecular shape. The term dynamic stereochemistry applies to die topology of processes which effect a structural change. The cases that are most important in organic chemistry are chemical reactions, conformational changes, and noncovalent complex formation. In order to understand the stereochemical aspects of a dynamic process, it is essential not only that the stereochemical relationship between starting and product states be established, but also that the spatial features of proposed intermediates and transition states must account for the observed stereochemical transformations. 

When topological strategies are used concurrently with other types of strategic guidance several benefits may result including (1) reduction of the time required to find excellent solutions (2) discovery of especially short or convergent synthetic routes (3) effective control of stereochemistry (4) orientational (regiochemical) selectivity (5) minimization of reactivity problems and (6) facilitation of crucial chemical steps. 

Not infrequently, when multiple FGI transforms must be used to establish the retron for a disconnective transform, as in the illustration shown just above, there may be alternative orderings of the FGI steps. Although the optimum ordering generally must be determined for each individual situation, it generally is dictated by considerations of topology, stereochemistry. 

Roseophilin (273), a deeply red-colored pentacyclic compound isolated from the culture broth of Streptomyces griseoviridis, is a novel antitumor antibiotic. Compound 273 possesses a topologically unique pentacyclic skeleton, consisting of a 13-membered macrocycle incorporated in an ansa-bridged azafulvene, which in turn is linked to a conjugated heterocyclic ring system. The absolute stereochemistry of roseophilin, as depicted in Fig. 9, was unknown until the first total synthesis published by Tius and Harrington in 2001 [125]. All syn-... 

The structure of (+)-phomactin A was determined using both NMR and crystallographic methods (Fig. 8.1). Although the crystal structure is of low quality, it clearly revealed the unusual ABCD-tetracyclic topology as well as the absolute stereochemistry. Subsequently, nine additional phomactins were isolated from various fungal sources with many of them displaying anti-PAF activity [3-5] B [3], B1 [3], B2 [3], C [3] (or Sch 47918 [6]), D [3], E [4], F [4], G [4], and finally, H [5] (Fig. 8.2). 

The field of stereochemistry serves as a unifying theme for the expanded definition and diversification of chemistry. The consequences of molecular and macromolecular shape and topology are central to issues of chemical reactivity, physical properties, and biological function. With that view, the importance of stereochemistry had never been greater, and it is hoped that this series will provide a forum for documentation of significant advances in all of these subdisciplines of chemistry. 

Our definitions of the stereoisomeric center, line, and plane all stipulate the existence of bonds between the ligating element and its ligands. The exclusive use of these elements limits our analysis to classical stereochemistry and thus does not encompass the so-called topological isomerism (47) of interlocked rings—catenanes (48)—or of knots. As there is no bond between the rings of the catenanes we cannot expect to handle such compounds with a system based on connectedness. At the present stage of development, this limitation in scope... 

Protein polymers based on Lys-25 were prepared by recombinant DNA (rDNA) technology and bacterial protein expression. The main advantage of this approach is the ability to directly produce high molecular weight polypeptides of exact amino acid sequence with high fidelity as required for this investigation. In contrast to conventional polymer synthesis, protein biosynthesis proceeds with near-absolute control of macromolecular architecture, i.e., size, composition, sequence, topology, and stereochemistry. Biosynthetic polyfa-amino acids) can be considered as model uniform polymers and may possess unique structures and, hence, materials properties, as a consequence of their sequence specificity [11]. Protein biosynthesis affords an opportunity to completely specify the primary structure of the polypeptide repeat and analyze the effect of sequence and structural uniformity on the properties of the protein network. 

OP—OR). Thus, chiral analogs of ATP can be utilized to study enzyme stereochemistry. Similarly, chiral sul-fones and sulfoxides have proved useful in assessing the topology of a protein s active site. 

With regard to fundamental principles I have shown the relation as well as the differences between the stereochemical treatment of low molecular weight and that of macromolecular compounds. If some confusion has resulted in the past, it is due to the improper use of concepts and of methods outside their proper held. Macromolecular stereochemistry can be subjected to physico-math-ematical approaches based on concepts of system and structure and on topological principles. Interesting developments in this regard were recently published by Danusso and co-workers (411-413). 

Stereospecificity is a hallmark of enzyme catalysis, so a knowledge of the basic principles of stereochemistry is essential for appreciating enzyme mechanisms. Stereochemical evidence can provide important information about the topology of enzyme-substrate complexes. In particular, the positions of catalytic groups on the enzyme relative to the substrate may often be indicated, as may be the conformation or configuration of a substrate or intermediate during the reaction. Further, comparison of the stereochemistry of the substrates and products may reveal the likelihood of intermediates during the reaction. 

The cis stereochemistry of spiro-(3-lactams 221 was established by NOE experiments and X-ray diffraction analysis. These spiro-(3-lactams would serve as important heterocyclic compounds possessing diverse scaffolds to which different functional groups could be fixed in a stereodefined 3D topological arrangement. 

Simon, J. Proc. Symp. Appl. Math. 1992,45, 97. Simon, J. A Topological Approach to the Stereochemistry ofNonrigid Molecules, in King, R. B. Rouvray, D. H. Eds., Graph Theory and Topology in Chemistry, Elsevier Amsterdam, 1987, pp. 43-75. 

A. Topological Stereochemistry Catenanes and Knots, the Topological Link... 

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