Problems with Literature Reporting of Synthesis Plans

The following pairwise examples of graphical depictions of chemical reactions illustrate item (f). 

The reader will find that the second entry in each example is far clearer than the first 

There are still other problems. There is a bias, even contempt, toward the use of any numerical analysis in the world of organic synthesis beyond the determination of percent reaction yield. Following are some reviewer comments that reflect this sentiment. As expected, the anonymous academic referee is more vitriolic than the industrial chemist. 

I strongly suggest the editors of Molecules not to accept this manuscript as the journal would endanger its seriousness within the community of chemists interested in total synthesis on a higher academic level.  

In this regard there is the humility factor associated with ranking. Many claims of conciseness, efficiency, or greenness are made on the basis of one or two criteria like overall yield, or step count, or one of the 12 green principles. Thorough metrics analyses often diminish claims made by authors that are based on a narrow view. 

---

Problems with Literature Reporting of Synthesis Plans... 

From the point of view of synthetic effort, preparation of combinatorial mixtures is by far the most economical approach. It can be done with ordinary laboratory equipment and does not take more time than the synthesis of any one of the individual components of the library. This simplicity, however, has its price firstly, the more components a mixture contains the more difficult it becomes to follow the reaction analytically and to determine the actual composition of the reaction product. Secondly, if hits are found in a biological assay, deconvolution is required. In most cases this is done via resynthesis either of the individual components or of subsets of the mixture. If the composition of the initial mixtures was carefully planned it may be possible to identify the active component(s) by simply comparing the composition of the active mixtures with those of the inactive ones. Corresponding procedures have been reported in the literature (e.g., the techniques of indexed [1,2] and orthogonal [3] chemical libraries have been used in solution-phase synthesis). However, the biological effect of a mixture may also be due to a combined action of several weakly active members, with the result that deconvolution does not identify a significantly active compound. Finally, the problem of impurities multiplies with the complexity of the mixtures. 

---