Synthesis plans

Program systems for computer-assisted organic synthesis (CAOS) have been under development since the early 1970s [27]. The program systems for computer-assisted synthesis planning can be subdivided into two groups information-oriented and logic-oriented systems [28]. 

The retrosynthetic analysis of a target compound is a systematic approach in developing a synthesis plan starting with the target structure and working backward to available starting materials. 

A chemist requires a large amount of l-bromo-2-pentene as starting material for a synthesis and decides to carry out an NBS allylic broinination reaction. What is wrong with the following synthesis plan What side products would form in addition to the desired product ... 

The polyene macrolide filipin was isolated in 1955 from the cell culture filtrates of Sterptomyces filipinensis, and was later shown to be a mixture of four components [36]. Although too toxic for therapeutic use, the filipin complex has found widespread use as a histochemical stain for cholesterol and has even been used to quantitate cholesterol in cell membranes [37]. The flat structure of filipin III, the major component of the filipin complex, was assigned from a series of degradation studies [38]. Rychnovsky completed the structure determination by elucidating the relative and absolute stereochemistry [39]. The total synthesis plan for filipin III relied heavily on the cyanohydrin acetonide methodology discussed above. 

Application of Green Metrics Analysis to Chemical Reactions and Synthesis Plans... 

Over the last decade there has been a vigorous attempt to answer quantitatively the simple question is a given reaction or synthesis plan green using the so-called green metrics . 

Experimental protocol is built into the construction of tree diagrams so that intermediates that are isolated are distinguishable from those that are made in situ, and the order of input dots matches the order of addition of reagents used in the synthesis plan. 

The required masses and raw material costs of any starting material or intermediate in a plan, including the final target product, may be determined by inspection. Overall kernel RME is shown to trump overall yield as the key metric to rank material efficiency of a synthesis plan. 

As an illustrated example of these ideas presented thus far we show in Scheme 4.8 and Figure 4.14 the conventional synthesis plan for triclosan and its corresponding synthesis tree diagram. 

Scheme 4.8 Convergent synthesis plan fortriclosan. Reaction conditions (i) acetyl chloride, AICI3 catalyst (ei = 94.3%) (i) 2CI2 (ef = 81 %) (ii) I/2K2CO3, CuCI catalyst, xylenes (s2 = 48.3%) (iii) 62.5% H2O2, 1/2 maleic anhydride, CH2CI2 ( 3 = 91.3%) (iv) MeOH, 35% HCI catalyst ( 4 = 94.5%). Molecular weights in g/mol are given in parentheses.

Figure 4.14 Synthesis tree for triclosan synthesis plan shown in Scheme 4.8. Molecular weights for each species are shown within parentheses.

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