The synthesis of organic molecules has long been a major
activity of organic chemistry, closely linked to biochemistry
for it involves the synthesis of natural products and or
test molecules for examining the parameters of biological
reactions. Nevertheless, it is astonishing how little we
know about the right way to design a synthesis of a new
molecule. It is easily shown that there are literally millions
of different routes possible, from different starting materials,
for the synthesis of any substance of interest, but there
has traditionally been no clear protocol to follow to design
the best one before going into the laboratory to try it.
We have been engaged for some years in creating a logic
for synthesis design, which has hitherto been only an art
in the midst of the otherwise systematic science of organic
chemistry. This has led to the creation of the computer
program SYNGEN which embodies logical principles to provide
the optimal synthetic sequences for any target molecule,
and has already had considerable success. This program of
computerizing organic chemistry logic welcomes young professionals
with an interest in combining the expertise of computers
with that of organic chemistry. Furthermore, it is of particular
interest also for those who wish to pursue the laboratory
execution of these syntheses, since they may expect to derive
especially short routes to molecules of biological or medical
interest from the computer and pursue these in the laboratory.
Parallel to the development of the SYNGEN program at the
computer, we have also a program in the laboratory for short
syntheses of various different natural products such as
morphine, lysergic acid, vitamin A, steroids, strychnine
and other indole alkaloids. For all of these we have created
synthetic routes notably shorter and more efficient that
those which have already been done, following our aim in
showing the importance of an optimal synthesis plan.
Selected Publications
Hendrickson, J.B., DeVries J.G. (1982). A Convergent Total
Synthesis of the Coenzyme Methoxatin. J. Org. Chem
47: 1148.
Hendrickson, J.B. Hussoin, Md.S. (1987). Seeking the Ideal
Dehydrating Agent. J. Org. Chem. 52: 4137.
Hendrickson, J.B. (1990). Organic Synthesis in the Age
of Computers. Angew. Chem. Intl. Ed. 29: 1286.
Hendrickson, J.B. (1992). Descriptions of Reactions: their
logic and applications. Rec. Trav. Chim. Pays-Bas
111: 323.
Hendrickson, J.B., Sander, T. (1995). COGNOS: A Beilstein-type
System for Organizing Organic Reactions. Eur. J. Chem.
1: 449.
Hendrickson, J.B.,Shih, I-L. (1997). A New Approach to
the Synthesis of Cortical Steroids, J. Chinese Chem.
Soc. 44: 133.
Hendrickson, J.B. (1997). Teaching Alternative Syntheses:
The Syngen Program," p. 214-231 in "Green Chemistry,"
ed. P. T. Anastas and T. C. Williamson, ACS Symposium Series
#626.
Hendrickson, J.B., Walker, M.A. (2000). A Two-Component
Pericyclic Reaction for Synthesis. Org. Letters 2:
2729-2731.
Hendrickson JB, Wang J. (2004) A new synthesis of lysergic
acid. Org Lett. 6:3-5.
Computer Programs:
WebReactions.net
Syngen2.chem.brandeis.edu
Last reviewed: April 4, 2005. E-mail comments or questions
to the webmaster.
