Computer‐assisted synthetic analysis. Quantitative assessment of transform utilities

Abstract

Abstract.A novel scheme for assigning initial, or substrate-independent, ratings for transforms (retroreactions) in the chemical knowledge base for the LHASA program for computer-assisted synthetic analysis is described. The new rating scheme is based on keyword scales defined for eight rating criteria. Initial ratings are calculated as weighted averages of the ratings in the eight categories. Various applications of initial ratings in LHASA are outlined.

Exploiting Enzymatic Dynamic Reductive Kinetic Resolution (DYRKR) in Stereocontrolled Synthesis

“…[16] [17] In fact, it is estimated that 10% of current drug syntheses rely on a biocatalytic step. [18] This underscores the need for the synthetic chemist to work from a set of retrosynthetic transformations that complements the traditional Corey-esque set [19] with a new set of biocatalytic transform arrows. Turner and coworkers refer to this complementary view as “biocatalytic retrosynthesis.” [20] …”

Reaction Databases and Synthesis PlanningCombined Application and Synergetic Effects

“…Synthesis planning tries to present or simulate possible reaction steps on the basis of special formalisms, facts, and rules. “Formalisms” can be formalized reactions, like transforms or synthons or mathematical models, “facts” are thermochemical or similar data, and finally “rules” can be mechanisms, heuristic algorithms, context descriptors, and so on. Synthesis planning makes suggestions about structural changes or transformations of educts into products, that is “what happens” and to some extent also “why it happens” but not about “how to do it”.…”

“…It has promoted thinking about strategy and tactics and the systematization and categorization of syntheses. Of course synthesis planning has gotten positive results in its own field: designing of new syntheses for target structures and successful reaction predictions (examples s ,,, ).…”

Using New Reasoning Technology in Chemical Information Systems

“…Numerical initial ratings were therefore replaced with a set of non-numerical statements about the different factors contributing to the utility of a reaction. 9 In the current version of LHASA, the transform writer grades factors such as typical yield, reliability (i.e., consistency of yield for different reactants), reputation (i.e., how often the reaction is reported in the literature), etc. on a scale of bad, poor, fair, good, very good, or excellent.…”