Sunday, May 6, 2012

ROBIA and Dolabriferol

Currie, R. H.; Goodman, J. M. Angew. Chem. Int. Ed. 2012, 51, 4695-4697: "In Silico Inspired Total Synthesis of (-)-Dolabriferol"
Socorro, I. M.; Goodman, J. M. J. Chem. Inf. Model. 2006, 46, 606-614: "The ROBIA Program for Predicting Organic Reactivity"
Socorro, I. M.; Taylor, K.; Goodman, J. M. Org. Lett. 2005, 7, 3541-3544: "ROBIA: A Reaction Prediction Program"

In 2005, Goodman and co-workers introduced the ROBIA (Reaction Outcome By Informatics Analysis) program for predicting the possible products of organic reactions and assessing the kinetic and/or thermodynamic feasibility of product formation. This program combines a series of rules based on typical reactivity patterns of certain organic functional groups with molecular mechanics and/or quantum chemical energy calculations on predicted products and/or transition state structures for possible reactions. Using this program, Goodman and co-workers predicted that (-)-dolabriferol might be formed - both biosynthetically and possibly synthetically - by a retro-Claisen reaction of a polyketide-derived precursor, i.e., they predicted that dolabriferol would likely be one of the major thermodynamic products of such a reaction. Now, Goodman and co-workers describe in ACIE a laboratory synthesis of (-)-dolabriferol that involves just such a (biomimetic) reaction (of a suitably protected precursor). This report not only showcases the utility of their modeling approach in the context of synthesis design, but also provides support for its utility in assessing the feasibility of biosynthetic proposals.