Heuristic principle

Intermolecular recognition and self-assembly processes both in the solid, liquid, and gas phases are the result of the balanced action of steric and electronic factors related to shape complementarity, size compatibility, and specific anisotropic interactions. Rather than pursuing specific and definitive rules for recognition and self-assembly processes, we will afford some heuristic principles that can be used as guidelines in XB-based supramolecular chemistry. 

Ernest Rutherford, Frederick Soddy, and then Sir William Ramsay documented natural transformations of one element into another in 1902 and 1903. The artificial transmutation of one element into another, however, was first accomplished in 1919 by Rutherford, a physicist. Indeed, the field of nuclear physics has contributed the most to our understanding of the subatomic world since the 1920s. But the scientists who most advocated transmutation as a goal of research and a heuristic principle for understanding the nature of matter—the Nobel Prize winners Ramsay and Soddy, and, in a less prominent way, Sir William Crookes—were chemists, not physicists.1... 

Equation (104) offers a concise representation of metabolic networks that is more accurate than a usual linear approximation but still amendable to analytical treatment. Importantly, the parameters retain their biochemical interpretability and may thus be chosen according to heuristic principles. 

Similar to generalized mass-action models, lin-log kinetics provide a concise description of biochemical networks and are amenable to an analytic solution, albeit without sacrificing the interpretability of parameters. Note that lin-log kinetics are already written in term of a reference state v° and S°. To obtain an approximate kinetic model, it is thus sometimes suggested to choose the reference elasticities according to simple heuristic principles [85, 89]. For example, Visser et al. [85] report acceptable result also for the power-law formalism when setting the elasticities (kinetic orders) equal to the stoichiometric coefficients and fitting the values for allosteric effectors to experimental data. 

In the same way that syllogisms and theorems are the essence of analytical reasoning, the "heuristic principles" are the essence of synthetical reasoning. 

SYNTHETIC STRUCTURAL ANALYSIS. SIMPLIFICATION. HETEROLYTIC DISCONNECTIONS HEURISTIC PRINCIPLES... 

Another important "heuristic principle" regarding functional groups, refers to the necessity of examining all possible pairs of functional groups (HP-2) in order to detect ... 

According to these heuristic principles, a possible synthesis of prostaglandins that proceeds via an aldol condensation in the last step, would be in principle valid for synthesis of prostanoids of the A and the B series (26a or 26b). but not for those of the E series owing to the great unstability of the resulting aldol (P-hydroxyketone or 1,3-C system) under the reaction conditions [20] (Scheme 4.7). 

Finally, also in connection with functional groups, there is a set of heuristic principles" which refer to the stability of aromatic and conjugated systems, as well as to the relationship between more or less unsaturated cyclohexane rings and benzene rings ("HPs-6"). For instance, through a series of well known reactions, it is possible to establish a relationship between p-methylanisole and cyclohexane derivatives with different levels of unsaturation (Scheme 4.13) ... 

Finally, another important heuristic principle is to carry out the systematic disconnection of substituted nucleophilic heteroatoms (O, N, S) directly attached to the carbon skeleton, especially if they are attached to a primary sp carbon atom (HP-8) ... 

In the synthesis of cephalosporine C (4i) by Woodward [34], the application of this simple heuristic principle allowed the direct establishment of a valid synthetic scheme which starts from L-(+)-cysteine (42) (Scheme 4.17) ... 

In fact, this heuristic principle (HP-8), which refers to nucleophilic heteroatoms directly attached to sp carbon atoms, may be also applied to nucleophilic heteroatoms directly attached to sp olefinic carbon atoms. In such cases, however, rather than a "disconnection" we would have an "unri-elimination" which will afford the substituted heteroatom as the "nucleofuge" and a triple bond as the "electrofuge". 

Bifunctional systems In the case of bifunctional systems (or molecules) only two alternatives are possible the bifunctional relationships are either "consonant" or "dissonant" (apart from molecules or systems with functional groups of type A to which we have referred to as "assonant"). In the first case, the synthetic problem will have been solved, in principle, in applying the "heuristic principle" HP-2 that is to say, the molecule will be disconnected according to a retro-Claisen, a retro-aldol or a retro-Mannich condensation, or a retro-Michael addition, proceeding if necessary by a prior adjustment of the heteroatom oxidation level (FGI). 

As we have seen in some of the examples already commented on in the preceding Chapters, the same "heuristic principles" which apply to acyclic compounds may also be applied, in principle, to cyclic compounds. The bond disconnections lead to acyclic systems or, at least, to a reduction in the cyclic order. 

In principle, the same "heuristic principles" which apply to carbocyclic compounds are also applicable to heterocyclic systems [29]. However, it must be kept in mind that ... 

Since in the synthesis of heterocyclic compounds the ring closure usually involves the formation of the carbon-heteroatom bond, in the retrosynthetic analysis the first bond to be disconnected is the carbon-heteroatom bond (Cf. heuristic principle HP-8), either directly or after the pertinent (FGI or FGA) functional group manipulation. For instance, compound 17 -which is the starting material for Stork s synthesis of Aspidosperma alkaloids [30]- may be disconnected as shown in Scheme 6.11. 

Up to now, we have seen how the "heuristic principles" can be applied to both linear and cyclic systems which we could call "normal systems". When some unusual structural features -such as quaternary carbon atoms, medium-sized rings or bridged systems- are found in the molecular structure under consideration, one may assume that they are derived either from a rearrangement or from an internal fragmentation [1]. 

The same "heuristic principles" which are applied to carbocyclic compounds also hold true for simple heterocyclic compounds containing one heteroatom. However, in the case of bridged heterocyclic molecules a modified strategic bond selection must be applied. Besides the strategic bonds which meet Corey s six rules, the bonds directly attached to nucleophilic heteroatoms -such as O, S and N-are also strategic Cf. heuristic principle HP-7), provided that they satisfy rules 2B, 4, 5 and 6. For instance, in compound 31a besides the five strategic bonds determined by rules 1-6 (cf. compound 26), the sixth darkened C-N bond in 31b is also a strategic bond. 

From an exhaustive retrosynthetic analysis and from the experimental work performed by Curran [29] [32], it was clear that the synthesis of modhephene required an elaborate strategy. In the first place, the tandem radical cyclisation should be conducted individually rather than just in one step since it allows more flexibility. In the second place, Curran s observation that the precursor of modhephene (54) could be the olefmic exocyclic derivative 55 allows the application of a series of heuristic principles already familiar to us, which greatly simplifies the retrosynthetic analysis and leads to diquinane and, finally, through a second radical retroannulation to the very simple cyclopentanone derivative (Scheme 7.24). 

The retrosynthetic analysis proceeds according to Scheme 13.4.1 and starts with the application of the heuristic principle number 8 (HP-8) i.e., performing the systematic disconnection of the nucleophilic heteroatom attached to the carbon backbone. Of the three bonds connecting the nitrogen atom, bond a is the most... 

The program CHAOS has been mainly developed as a didactic tool i.e., as a heuristic aid for designing organic syntheses in such a manner that the student may use it, at his own pace, at different levels following the heuristic principles and methodologies developed in the present book. Two versions of CHAOS, one for IBM PCs (or "fully compatible" PCs) with Windows 3.1 or later, and another one for Macintosh computers are available. A summary of some of the main improvements of the present versions follows ... 

The heuristic principles which have been implemented into the program are based in the fact that ... 

Some new examples to illustrate the heuristic principles have been incorporated (Chapter 4, for instance)... 

The choice of an optimal name for a given molecule is based on the heuristic principles of shortness and simplicity. 

However, by examining the adsorption behavior of polypeptides and proteins with comparable porous and nonporous particles in finite baths, packed columns and expanded or fluidized beds, an iterative simulation approach based on the heuristic principles described earlier and along the lines of the flow diagram shown in Fig. 32 can be developed, leading ultimately to the implementation of useful scale-up criteria. Along the way, computer simulations, generated from the analysis of the concentration-time... 

At this point Born argues that 20th century physics has celebrated its greatest triumphs by eliminating all concepts that are of no relevance for the observed phenomena. He points out that elimination of the concept of absolute space and time leads to the theory of relativity, and elimination of the concept of the possibility of simultaneous accurate measurement of conjugate dynamical variables leads to quantum mechanics. He calls this process of elimination the heuristic principle of physics . Following the heuristic principle, he demands the elimination of the concept of determinism as a physical concept even in classical mechanics and wonders what it might lead up to. 

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