The synthetic path

A fundamental principle is that a synthetic path should be short, i.e. contain as few reaction steps as possible. It is also desirable that the path should be convergent, which means that larger parts of the target structure are prepared through separate paths and then joined together in a later coupling step. This is a consequence of the economy of yield (and time). 

As the number of known chemical reactions is very large and the number of known chemical compounds is even larger, the number of possible combinations of chemicals and reactions will be overwhelming. This points to a problem, viz. how to establish efficient paths to link available starting material to the desired target. Often more than one path can be conceived. The different paths will deftne the tree of available routes from the starting materials to the target shown in Fig. 1.3. 

It is in principle possible to plan multistep synthesis in two directions  

which can be nitro, cyano, keto, carboxylic ester. .. The actual precursors, i.e. 

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The first effective strategy is the introduction of axial assistant coordination ligands to the central metal atoms of Pcs [25-48]. The synthetic paths of this type of... 

Impressive, highly ordered centimetre-sized fibres are obtained whose synergistic growth mechanism based on the kinetic cross-coupling of a dynamical supramolecular self-assembly and a stabilizing silica mineralization may well be the basis of the synthetic paths used by Nature to obtain its materials with well-defined multiscale architectures in biological systems. 

Obviously the determination of nd can be of help in the synthetic path. It is interesting to note that the substitution of the central benzene ring in dendrimers of the type illustrated in Scheme 7 for a [Fe( 5-C5H5) (>76-C6R6)]+ group affords dendrimers of the type illustrated in Scheme 8.49... 

Schmidt 90) succeeded in 1968 in preparing S7, the first sulfur ring with an odd number of atoms. The synthetic path employed for preparing Sg and S12 does not provide high yields, thus a new method had to be found. The reaction... 

The synthetic paths of fluorinated porphyrins (fluorine atoms or fluoroalkyl chains) are numerous and depend on the fluorination site (periphery or meso position). These syntheses are performed through the use of fluoroalkylated pyrroles, through DAST fluorination, or through direct perfluoroalkylation. Some examples are given next. 

Similarly, the mixed homodetic/heterodetic bicyclic structures containing a disulfide bridge are preferably produced as monocyclic compounds that are then typically oxidized in solution adopting standard procedures as described in Section 6.1.1 (Scheme 23, path Bl). If even disulfide formation is performed on resin by the procedures reported in Section 6.1.2, an additional level of selective protection is required for the cysteine thiol functions. The synthetic paths Bl and B2 are also applicable for the synthesis of type II and III bicyclic peptides, independent of whether only lactam bridges are produced or mixtures of lactam/ disulfide bridges. 

Asymmetrical, Mixed Bisporphyrinates - The synthetic paths (paths — f, — j, k) preclude an easy synthesis of heterobimetallic complexes like RuOs(OEP)2. Such complexes were obtained in pure forms by stepwise metallation of H2(DPB) to RuOs(DPB) [232]. Separation of a mixture of [Ru(OEP)]2, [Ru(OETAP)]2, and Ru2(OETAPXOEP) was achieved by stepwise oxidation of these bis-metalloporphyrins using AgBF4 in toluene when first [Ru(OEP)]2BF4 and then [Ru2(OETAP)(OEP)]BF4 precipitated. The latter was then reduced with cobaltocene to give pure Ru2(OETAP)(OEP) [233]. 

As discussed in some detail on p. 202 of this review, the enantiomers (-)-HU-210 (which retains the stereochemistry present in THC) and (+)-HU-211 were originally prepared in order to establish whether the activity of the cannabinoids is stereospecific. The synthetic path is shown in Figure 5.2 [25], The intermediate ketones (5 and enantiomer) can be easily crystallized to absolute purity and therefore the final products HU-210 (3) and HU-211 (4) are obtained with e.e. higher than 98.8%. This was a central aim of our synthetic approach in order to make possible the eventual therapeutic use of the [35,4S] enantiomer (4), as the presence of traces of the highly psychotropic [3/J, 4/ ] enantiomer (3) could lead to undesirable side-effects. The enantiomeric purity of thrice recrystallized (3) and (4) was established by h.p.l.c. analysis of the diastereoisomeric bis(MIPA) esters obtained by reaction with (S)-(+)-a-methoxy-a-(trifluoromethyl)phenylacetyl (MTPA) chloride. As expected, we found that HU-211 (4) has no cannabimimetic activity [20-24], However, unexpectedly, we observed that it exhibits pharmacologi-... 

The synthetic path a of Fig. 153 makes it possible to obtain, by polyaddition, variously substituted polyenes (394, Fig. 154) starting from styrenic - or acrylic, mainly acrylamidic, monomers. In particular, the vinyl-P-aiylamino propiophenones are prepared from the corresponding Mannich base by amino group replacement and arc used in the synthesis of polymers 390 via copolymerization with styrene. Analogous derivatives are obtained by copolymerization with acrylamides. - " ... 

Trilostane blocks the synthetic path earlier (3p-hydroxysteroid dehydrogenase) and thus also inhibits aldosterone synthesis. 

Errors in pruning also cause significant problems. Omitted pruned paths generally resulted from our not using reaction rule constraints or nonselective and/or non-intelligent use of the rules. This is one reason why none of SYNLMA s paths represent published syntheses of Ibuprofen (15) in spite of the fact that the requisite rules were in the data base. On the positive side, the synthetic paths to Ibuprofen discovered by SYNLMA are straightforward and would probably work as shown. 

Compare the synthetic paths leading from acetyl CoA to mevalonate and to the ketone bodies. Note the role of 3-hydroxy-3-methylglutaryl CoA reductase (HMG CoA reductase) as the major regulatory enzyme in cholesterol biosynthesis. 

The synthetic path to the IHPS thus consists of introducing intramole-cularly a large number of rigid crosslinks between the different repeat units of a single linear polymeric chain taken in the form of a coil in a dilute solution. In this way one can expect to arrive at a hypercrosslinked structure on a (macro)molecular level. 

This section will describe some of the synthetic methods of selected PTs and PSTs. Examples of the different synthetic routes that are used to aehieve thiophene-based polymers with variable properties will be noted. The latter examples will also include monomer synthesis as this leads into the synthetic path chosen in many of the cases. The experimental procedures and characterization details will be included. 

There has been much recent interest in the preparation of various inorgairic solids (notably aluminium phosphates) with controlled porosity in the microporous and mesoporous range [1], in ways analogous to that used in the synthesis of aluminosilicate zeolites. For the synthesis of mesoporous solids, the synthetic paths make use of long chain surfactant molecules. At the University of Cyprus there is a long-standing interest in the synthesis and study of porous ceria [2-4], because of the importance of that solid in several catalytic applications, and notably in automobile exhaust catalysts. In this presentation we discuss the use of aniline as the precipitating base instead of ammonia, which has hitherto been used. 

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