Synthetic consonance

In principle, the synthesis of a consonant molecule or a bifunctional relationship within a more complex polyfunctional molecule, does not offer too many difficulties. In fact, all the classical synthetic methods of carbon-carbon bond formation that utilise reactions which are essentially reversible, lead to consonant relationships. For instance, the book by H.O. House "Modem Synthetic Reactions" [22], after dealing, for almost 500 pages, with functional group manipulations, devotes the last 350 pages to carbon-carbon bond formation, all of which lead to consonant relationships. These methods can, actually, be reduced to the following four classical condensations (and their variants) Claisen condensation, aldol condensation, Mannich condensation and Michael addition (Table 2.5). 

Table 2.5. Classical synthetic methods leading to consonant relationships...

Keeping in mind "generalisation 3" concerning the priority of the carbon skeleton over the oxidation state of the functional groups (or even of the carbon chain itself), the synthesis of a consonant molecule (or system) with n bonds between the two functional groups has, in principle, n possible different synthetic pathways. For instance, the 1,3-amino-ketone,... 

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). 

In contrast, the so-called bis-nor-Wieland-Miescher ketone (2) is a more complex synthetic problem, since the molecule is a multidissonant system with two dissonant bifunctional group relationships (1,4-D and 1,6-D) and two dissonant cyclopentane rings, besides a 1,5-consonant bifunctional group relationship. Its synthesis was only accomplished 30 years after the synthesis of its consonant homologue [5],... 

Remember, however that CHAOS does not intend to be a database of "synthetic methods" presently available to organic chemists. CHAOS is aimed at finding the intermediate precursors of the "synthesis tree" by means of selected basic disconnections (either "consonant" or "dissonant"). In the author s view, it is of minor importance, for instance, how a "carbene" -resulting from a -(2 + 1) cycloelimination- is generated, or whether a double bond is the direct result of a Wittig reaction or the dehydration of an alcohol formed in a Grignard reaction. In... 

Process automatically the structure of the alkaloid porantherine, first with the "default-order" of disconnections and then giving priority to "consonant" over "rings" disconnections. In the latter case you should "Save" only the intermediate precursors leading to the same synthetic sequence and the same starting material (A) used in Corey s synthesis, which was actually found by LHASA (see ref. 19, Chapter 12). 

Age-adjusted mortality rates for cancer at different sites in U.S. males are shown in Figure 1. It is evident from these data that cancer of the lung has steadily increased in males since 1935 corresponding to an approximate 20-year lag period after cigarette smoking first became popular. In marked contrast to this, the incidence of cancers of the colon and rectum, breast and prostate have increased only at a low rate since 1940. We logically conclude that industrial pollution, food additives, synthetic chemical products, etc., the levels of which have increased dramatically in our environment, are not associated with the development of these three cancer types. On the other hand, the mode of cooking has remained similar over this period, and thus is consonant with the cancer incidence data. 

O-tnethyl oxime and 252A a hydroxy O-methyl oxime, as shown in Fig. 19. The configuration of the 0-methyloxime is not rigorously established, but it appears to be as shown for 236 and 252A (/5i). Reduction of 236 with sodium in butanol afforded a primary amine, consonant with the oxime structure of 236 (/5i). Reduction of synthetic nitropolyzonamine (see below) yields the same primary amine (K. Hutchinson, H. M. Gar-raffo, T. F. Spande, and J. W. Daly, unpublished). 

Finally the introduction of cyclopropane or vinylcyclopropane into organic compounds provides an opportunity to cross the odd/even manifolds in further synthetic steps aimed at the preparation of compounds of increased molecular complexity. Traditionally, any synthesis that involves intermediates with an odd number of atoms is more difficult because proper charge parity or consonance cannot be observed. A cyclopropane unit then functions as a topological operator in those cases where such crossover is desired. ... 

Although ESR data for chlorin and BPheo cation radicals provide clear evidence of macrocycle distortions consonant with crystallographic results for the parent compounds[21,33,34], it would obviously be more instructive to examine the solution properties of distorted porphyrins under conditions where the conformations observed in the crystalline state are maintained in solution. We have therefore examined a series of synthetic porphyrins in which different peripheral substituents were added in order to deliberately introduce steric crowding that would be maintained in solution[32,35,36]. An example of this approach is shown... 

---