Consecutive synthesis

An example of a convergent synthesis used by Fuchs[2] for the synthesis of prostaglandin Ea (PGE2) is illustrated in Chart-2, while an example of consecutive synthesis used by Corey[3] for the synthesis of prostaglandin E2 (PGE2) is illustrated in Chart-3. 

Figure 25.14 illustrates the difference between a consecutive and a convergent synthesis. In the consecutive synthesis, a single starting material is... 

If there is 1.0 mol of starting material and the yield of each step in the consecutive synthesis is 90%, how many moles of the target will be obtained ... 

Each intermediate in retrosynthetic analysis is a new target molecule, and combination, in the last step, of the last two intermediates into the TM corresponds to highly convergent synthesis, the advantages of which, compared to consecutive synthesis, have been repeatedly discussed in textbooks on organic synthesis. 

In the conversion of methyl caffeate to 3-cyclohexylpropyl caffeate in the consecutive synthesis, therefore, the reverse reaction with methanol would occur easily to decrease the amount of the desired product. We tested the effect of methanol on Novozyme 435, and observed that methanol had an inhibitory effect on the production of 3-cyclohexylpropyl caffeate (Fig. 11). 

In the consecutive synthesis, the methyl caffeate was transesterified efficiently to 3-cyclohexylpropyl caffeate by Novozyme 435 with deactivation of chlorogenate hydrolase by taking advantage of the difference between the optimum temperatures for chlorogenate hydrolase (40°C, Fig. 4) and Novozyme 435 (80°C, Fig. 7). 

Clearly, for symmetry reasons, the reverse process should also be considered. In fact, early versions of our reaction prediction and synthesis design system EROS [21] contained the reaction schemes of Figures 3-13, 3-15, and 3-16 and the reverse of the scheme shown in Figure 3-16. These four reaction schemes and their combined application include the majority of reactions observed in organic chemistry. Figure 3-17 shows a consecutive application of the reaction schemes of Figures 3-16 and 3-13 to model the oxidation of thioethers to sulfoxides. 

The EROS (Elaboration of Reactions for Organic Synthesis) system [26] is a knowledge-based system which was created for the simulation of organic reactions. Given a certain set of starting materials, EROS investigates the potential reaction pathways. It produces sequences of simultaneous and consecutive reactions and attempts to predict the products that will be obtained in those reactions. 

FIGURE 11.1 The fundamental process of information transfer in cells. Information encoded in the nucleotide sequence of DNA is transcribed through synthesis of an RNA molecule whose sequence is dictated by the DNA sequence. As the sequence of this RNA is read (as groups of three consecutive nucleotides) by the protein synthesis machinery, it is translated into the sequence of amino acids in a protein. This information tmiisfer system is encapsulated in the dogma DNA RNA protein. 

A synthetic approach to the same tetracyclic y-carboline nucleus (235) is the consecutive Fischer indole and Bischler-Napieralski ring closure of o-acetamidoacetophenone methylphenyUiydrazone (234). The Bischler-Napieralski reaction has also been used in the synthesis of 3,4-benz-j8-carbolines (236) and 3,4-benz-3-carbolines, e.g. 237... 

The reaction of a cyclic ketone—e.g. cyclohexanone 1—with methyl vinyl ketone 2 resulting in a ring closure to yield a bicyclic a ,/3-unsaturated ketone 4, is called the Robinson annulation This reaction has found wide application in the synthesis of terpenes, and especially of steroids. Mechanistically the Robinson annulation consists of two consecutive reactions, a Michael addition followed by an Aldol reaction. Initially, upon treatment with a base, the cyclic ketone 1 is deprotonated to give an enolate, which undergoes a conjugate addition to the methyl vinyl ketone, i.e. a Michael addition, to give a 1,5-diketone 3 ... 

Consecutive Michael additions and alkylations can also be used for the diastereoselective synthesis of 5- and 6-membered ring systems. For instance when 6-iodo-2-hexenoates or 7-iodo-2-heptenoates are employed the enolate of the Michael adduct is stereoselectively quenched in situ to provide the cyclic compound with trans stereochemistry (>94 6 diastereomeric ratio). As the enolate geometry of the Michael donor can be controlled, high stereoselectivity can also be reached towards either the syn or anti configuration at the exocyclic... 

In contrast to the synthesis of carbocyclic rings, the Cope rearrangement has been used sparsely for generating azepinones. Recently, the enantioselectivity of the conversion of 2-aza-divinylcyclopropane 286 has been investigated. The synthesis started from the optically active cyclopropanecarboxylic acid (90% ee), which had been converted into the isocyanate 286 by initial azidation to 285 and a consecutive Curtius rearrangement. Furthermore, the conditions of the iso-... 

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