Chirality stereocenter

Due to their fermentative synthesis, natural PHAs are strictly isotactic, featuring exclusively (/ )-configuration at the chiral stereocenter in the main chain. However, PHAs vary in their mechanical properties and can be grouped into two subcategories ... 

The stereochemistry of step polymerization is considered now. Bond formation during step polymerization almost never results in the formation of a stereocenter. For example, neither the ester nor the amide groups in polyesters and polyamides, respectively, possess stereocenters. Stereoregular polymers are possible when there is a chiral stereocenter in the monomer(s) [Oishi and Kawakami, 2000 Orgueira and Varela, 2001 Vanhaecht et al., 2001], An example would be the polymerization of (R) or (S)-H2NCHRCOOH. Naturally occurring polypeptides are stereoregular polymers formed from optically active a-amino acids. 

It is also possible for a molecule to be chiral without having actual point chirality (stereocenters). Commonly encountered examples include l,r-bi-2-naphthol (BINOL) and 1,3-dichloro-allene which have axial chirality, and (E)-cyclooctene which has planar chirality. 

Ethyl-2-methyl-l,6-dioxaspiro[4.5]decane is a pheromone produced by two varieties of bees, Parvespula vulgaris L. and Andrena haemorrhoa F. The 27 , 57 , 77 -isomer (188) has been synthesized using 147, ultimately derived from ethyl L-lactate, to supply the chiral stereocenter at C-2 (Scheme 26) [19]. The second chiral intermediate 185 is derived from (5)-( — )-malic acid. 

R, S ) diastereomers with complete selectivity. Moreover, for the compounds containing three chiral stereocenters there was considerable stereoselectivity in favor of the (R, S )-anti diastereomer. For (56 X — AsPh), (R, S )-syn (R, S )-anti =5 4 for (56 X = PPh) and for (59), the corresponding ratios were 5 1 and 100 1 (no detection of minor diastereomer by NMR spectroscopy), respectively. The chelating (R, S ) diastereomers in each case were identified by preparing molyb-denum(O) carbonyl derivatives. The R, S )-syn diastereomers of the ligands gave fully coordinated /ac-tricarbonylmolybdenum complexes and the R, S )-anti forms the As2- or Pj-chelated cis-tetracarbonylmolybdenum complexes. 

If compounds have the same topology (constitution) but different topography (geometry), they are called stereoisomers. The configuration expresses the different positions of atoms around stereocenters, stereoaxes, and stereoplanes in 3D space, e.g., chiral structures (enantiomers, diastereomers, atropisomers, helicenes, etc.), or cisftrans (Z/E) configuration. If it is possible to interconvert stereoisomers by a rotation around a C-C single bond, they are called conformers. 

Antineoplastic Drugs. Cyclophosphamide (193) produces antineoplastic effects (see Chemotherapeutics, anticancer) via biochemical conversion to a highly reactive phosphoramide mustard (194) it is chiral owing to the tetrahedral phosphoms atom. The therapeutic index of the (3)-(-)-cyclophosphamide [50-18-0] (193) is twice that of the (+)-enantiomer due to increased antitumor activity the enantiomers are equally toxic (139). The effectiveness of the DNA intercalator dmgs adriamycin [57-22-7] (195) and daunomycin [20830-81-3] (196) is affected by changes in stereochemistry within the aglycon portions of these compounds. Inversion of the carbohydrate C-1 stereocenter provides compounds without activity. The carbohydrate C-4 epimer of adriamycin, epimbicin [56420-45-2] is as potent as its parent molecule, but is significandy less toxic (139). 

The example given above of the selection of deoxycholic acid as a SM for the synthesis of cortisol also illustrates the use of a chiral natural substance as synthetic precursor of a chiral TGT. Here the matching process involves a mapping of individual stereocenters as well as rings, functional groups, etc. The synthesis of helminthosporal (105) from (-i-)-carvone (106)21 and the synthesis of picrotoxinin (107) from (-)-carvone (108)22 amply demonstrate this approach employing terpenes as chiral SM s. 

Spatial and/or coordinative bias can be introduced into a reaction substrate by coupling it to an auxiliary or controller group, which may be achiral or chiral. The use of chiral controller groups is often used to generate enantioselectively the initial stereocenters in a multistep synthetic sequence leading to a stereochemically complex molecule. Some examples of the application of controller groups to achieve stereoselectivity are shown retrosynthetically in Chart 19. 

Enantioselective processes involving chiral catalysts or reagents can provide sufficient spatial bias and transition state organization to obviate the need for control by substrate stereochemistry. Since such reactions do not require substrate spatial control, the corresponding transforms are easier to apply antithetically. The stereochemical information in the retron is used to determine which of the enantiomeric catalysts or reagents are appropriate and the transform is finally evaluated for chemical feasibility. Of course, such transforms are powerful because of their predictability and effectiveness in removing stereocenters from a target. 

Identify segments of nCL stereocenters which in some degree map onto available chiral predecessors in order to generate a chiral S-goal. 

Chiral Controller. (Synonymous with Chiral Auxiliary). A chiral structural unit which when attached to a substrate enhances stereoselectivity in the formation of new stereocenter(s). 

The most valuable characteristic of the Patemo-Buchi reaction is the ability to set multiple stereocenters in one reaction and the development of diastereocontrolled reactions has been a major theme of research concerning this reaction. Stereocontrol can be envisioned to spring from either the carbonyl or the alkene and be controlled by either the substrate directly or by a chiral auxiliary. Little success has been achieved in substrate-induced selection by the carbonyl the most successful results were produced by... 

Ironically, auxiliary-induced control via the alkene failed to generate synthetically useful selectivities, but direct substrate-induced control did. In particular, chiral silyl enol ethers with stereocenters in the y-position allowed the synthesis of enantiomerically... 

Cleavage of the chiral auxiliary is effected in a three-step procedure commencing with quatemization of the nitrogen with methyl fluorosulfonate, methyl trlfluoromethanesulfonate, or trimethyloxonium tetrafluoroborate. Reduction of the corresponding iminium salt 19 with NaBH4 and acidic hydrolysis of the resulting product affords substituted aldehyde 5 without epimerization of either stereocenter. 

Oxathiane 101 is readily deprotonated using s-BuLi, and the resulting anion reacts with alkyl halides, ketones, and benzonitrile (85JOC657). The majority of work in this area, however, is due to Eliel and coworkers and has involved chiral 1,3-oxathianes as asymmetric acyl anion equivalents. In the earliest work it was demonstrated that the oxathianes 102 and 103, obtained in enantiomeri-cally pure form by a sequence involving resolution, could be deprotonated with butyllithium and added to benzaldehyde. The products were formed with poor selectivity at the new stereocenter, however, and oxidation followed by addition... 

Sinnlarly, f-i- -casuralme, a pentahydroxy pyrrolizidine alkaloid, is prepared by a tandem [4-i-3 /[3-i-3 cycloadchdon involving nitroalkene, chiral vinyl ether, and vinyl silane This process creates five of the six stereocenters present in this potent glycosidase inhibitor fScheme 8 35 ... 

The most common, although not the only, cause of chirality in an organic molecule is the presence of a carbon atom bonded to four different groups—for example, the central carbon atom in lactic acid. Such carbons are now referred to as chirality centers, although other terms such as stereocenter asymmetric center, and stereogenic center have also been used formerly. Note that chirality is a property of the entire molecule, whereas a chirality center is the cause of chirality. 

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