Subject: SUMMARY - Reaction Pathway Programs, Part II

From: [email-masked] (Joe Golab)
Date: Tue, 22 Jul 1997 08:30:27 -0500

Hi CCL:

Below is an updated summary of responses to the "retro-synthesis" question
I asked on 7/21.  Thanks to all who have responded.  I have edited some of
the answers and so I take full responsibility for any errors.  Some good
references are in the replies themselves, i.e. I did not bother to summarize
them.  If I get any more answers, I will re-post summary.

<<Tue Jul 22 08:24:32 CDT 1997>>

Execute Summary of Answers

  1) SYNGEN, Jim Hendrickson, Brandeis University
  2) CAMEO, Bill Jorgensen, Yale  (<-- Reaction Simulation)
  3) SYNTREE, Commerical Software, Vendor?
  4) SYNLIB, Dan Chodosh, may not exist anymore
  5) REACCS, MDL
  6) CAS's reaction data base
  7) Chiron, Steve Hannisan (spl?) of U. of Montreal.
  8) LAHSA, E.J. Corey, Harvard U.
  9) Unknown, Michael Mavrovouniotis, Northwestern
 10) Crossfile, Beilstein
 11) EROS, Dr. Johann Gasteiger, Erlangen University.
 12) ORAC, Pergamon.
 13) SECS W. Todd Wipke, University of California, Santa Cruz.
 14) WODCA, J. Gasteiger.
 15) IGOR/RAIN, Ugi
 16) PASCOP, Gerard Kaufmann, University of Strasbourg
 17) SYNCHEM, H. Gelernter U.S. Stony Brook

______________________________ Original Note __________________________________
Subject: CCL:Reaction Pathway Program
Author:  chemistry-request ([email-masked]) at unix,sh
Date:    7/14/97 4:43 PM

Dear CCL Member:

Do you know of any (engineering, chemistry, biological, etc) program that
given a compound would suggest any and all reaction pathways toward that
compound (no matter how outlandish from a thermodyanmic standpoint)?

For example, given tolune, the program would suggest:

 1) benzene + methane -> toluene
 2) methylcyclohexane -> toluene + H2
 3) methane + heat/pressure -> toluene + H2
 4) ETC.

Perhaps this is really a database that is part of a program.  Any leads
would be gratefully appreciated!  Thanks.

:Joe Golab, [email-masked]

_____________________________Reply Separator_________________________________
Subject: Re: CCL:Reaction Pathway Program
Author:  lchen ([email-masked]) at unix,mime
Date:    7/14/97 5:16 PM

Dear Joe:

Please check the following SYNGEN site:

http://syngen2.chem.brandeis.edu/syngen.html

you may find something interesting you.

-Lingran

**********************************************************
Lingran Chen, Ph.D.
Senior Scientific Programmer
MDL Information Systems, Inc.
14600 Catalina Street
San Leandro
CA 94577

Phone: (510) 895-1313, Ext. 1305
FAX:   (510) 614-3616

Email: [email-masked]
URL:   http://www.mdli.com
       http://syngen2.chem.brandeis.edu/~chen/lingran.html
**********************************************************

_____________________________Reply Separator_________________________________
Subject: Re: CCL:Reaction Pathway Program
Author:  eslone ([email-masked]) at unix,mime
Date:    7/14/97 6:32 PM

Talk to Jim Hendrickson at Brandeis University.  He has a program called
SynGen.
___________________________________________________________________

 J. Eric Slone
 Scientific Consulting Services
 5500 Holmes Run Parkway, Suite 501
 Alexandria, Virginia  22304-2851

 Phone:  (703) 461-7078                  mailto:[email-masked]
 Fax:    (703) 751-6639        http://www.patriot.net/users/eslone
___________________________________________________________________

_____________________________Reply Separator_________________________________
Subject: Re: CCL:Reaction Pathway Program
Author:  dsmith ([email-masked]) at unix,mime
Date:    7/14/97 9:12 PM

Joe:

I am not familiar with any program that will suggest ALL reaction
pathways... there are just way too many possibilities, which is why we
still have synthetic organic chemists.

You are probably familiar with Bill Jorgensen's CAMEO program (I hope I
have the name correct), which can suggest 'reasonable' synthetic routes to
various types of compounds and functionality.  There is also a commercial
program (not that Bill doesn't sell his programs, ;)) called SYNTREE (I
believe).  There were some papers about this at either the last ACS
National meeting in San Francisco or at the Midland, MI, ACS Regional
meeting in May.  I can look for more information if you wish, but I am at
home and just finishing up a vacation while I write this.

Regardless, both of these programs use a combination (I believe) of data
bases and "expert" algorithms to select likely reactions.  I don't know of
anything that will give you all possible routes, except perhaps an
aggressive undergraduate who has just finished his/her organic final exam.

There was also SYNLIB that came from the late Dan Chodosh... I don't know
if anyone picked up that program so I can't tell you if it still exists.
This was purely data base based and matched based on user-defined
descriptors, if I remember correctly from my postdoc days.  MDL REACCS and
CAS's reaction data base are two others that come to mind.

I would also love to hear from anyone else about similar programs.  Please
post to CCL rather than just to Joe.

Doug Smith

--
Dr. Douglas A. Smith, President and CEO     |  voice: (814) 255-7859
The DASGroup, Inc.                          |    fax: (814) 255-3517
1732 Lyter Drive, 2nd Floor                 |  email: [email-masked]
Johnstown, PA 15905                         |    WWW: http://www.dasgroup.com

Contract R&D specialists in modeling, simulation, synthesis and risk
assessment for chemistry, materials science, and biotechnology.

_____________________________Reply Separator_________________________________
Subject: Re: CCL:Reaction Pathway Program
Author:  Willie ([email-masked]) at unix,mime
Date:    7/15/97 1:12 AM

Joe,

Two programs that can do retrosynthetic analysis,
1. Chiron, from Prof. Steve Hannisan (wrong spelling?) of U. of Montreal.
2. LAHSA, from prof. E.J. Corey of Harvard U.

--
Willie Cui, Ph.D.       voice 201-512-0486
MicroSimulations        fax:  201-512-0489
478 Green Mountain Rd.  email: [email-masked]
Mahwah, NJ 07430        URL:  http://www.microsimulations.com

_____________________________Reply Separator_________________________________
Subject: RE: Reaction Pathway Program
Author:  RICHEYFA ([email-masked]) at unix,mime
Date:    7/15/97 6:12 AM

Hi, Joe,

I had a similar question when looking for new routes to commodity
chemicals.  I found references to techniques for making expensive
[usually pharmaceutical] chemicals which would take a target structure
and elaborate[!] multistep pathways from known precursors.  I think one
was E.J. Corey's group's product.  At least one of these gave
synthetically viable guesses for transformations so probably weeded out
a lot of the thermodynamically infeasible routes.

I haven't pursued this very far but was left with the feeling that there
was a lot of work in the 80's and the only thing that has survived
outside academe has been the pharmaceutical part.  I may be wrong in
this.

I never did summarize my work but if you are interested I can send you
references with brief comments.

I wanted this approach to automate the cataloging of possible synthetic
routes including finding the ones that I'd overlook because of my
particular chemical background.

Forrest Richey

Union Carbide Corporation
Technical Center
Bldg 740 Room 4107
S. Charleston, WV 25303
(304)747-4964

Two things happen when you reach fifty, and if I could remember one, I
wouldn't worry about the other two.

_____________________________Reply Separator_________________________________
Subject: Reaction Pathways
Author:  burkhart ([email-masked]) at unix,mime
Date:    7/15/97 9:00 AM

Hi Joe,

If I'm not mistaken, Prof. Bill Jorgensen's group @Yale worked
on a program called CAMEO. As I remember it, they were trying
to use it as a reaction chemistry "assistant"--but I'm not
sure how far they got.

----------------------------------+------------------------------------
Papernet:  Craig W. Burkhart      | Baseball & summer--What could be
           Goodyear Research      | better? The birds are singing and
           142 Goodyear Blvd.     | the BATS are out!
           Akron, OH   44305      | Indians update: 48-37 (.564)
Mouthnet:  330.796.3163           | 'Best little .500 club' $60 mil
Faxnet:           .3304           | can buy... (swampland, anyone?)
Internet:  [email-masked] | Pitching REALLY Stinks!!! UGH!
----------------------------------+------------------------------------

_____________________________Reply Separator_________________________________
Subject: Re: CCL-Reaction Pathway Pro
Author:  mnliebman ([email-masked]) at unix,sh
Date:    7/15/97 9:59 AM

RE>CCL:Reaction Pathway Program              7/15/97

Joe
try contactine Michael Mavrovouniotis at Northwestern- [email-masked] I
think
Michael
271 7190
_____________________________Reply Separator_________________________________
Subject: Your e-mail to CCL
Author:  pierre ([email-masked]) at unix,mime
Date:    7/15/97 10:14 AM

Dear Joe,

I received a copy of your e-mail attached at the end of my reply. You may
remember that we talked on the phone a few month ago. Although my answer is
obviously biased by the fact that I work for MDL, my experience after 9
years working with the large pharma and chemical industries in Europe and in
the US is that there seems to be no good way to have a prediction program. A
lot of companies have tried, and they have ended up licensing our databases
or other  (like Beilstein Crossfire). The advantage they have found in our
system, compared to other database systems, (especially since we introduced
ISIS, the client server system we provide now) is the flexibility of our
querying interface. You can search not only on exact reactions, but also on
things like " find an example of a reaction where this fragment is formed".
Or "find an example of a reaction using these conditions where a fragment is
unaltered".

As an example, to address your query below, we would draw the toluene, and
define it as a product, and then we would perform a search known as
"structure as product not as reactant, or "sub-structure as product, not as
reactant". Which basically defines that the toluene has to be formed during
the reaction. You could also refine the query by specifying certain classes
of reactions you do not want (list catalysts that are expensive etc).

Running the query you use as an example on our databases leaded to 113
reactions out of 107 publications. The query was exclusively dealing with
the toluene as product, no substituted toluene was allowed. In some of these
reactions the benzene is a by product, and probably a lot of them are
dealing with cleavage from a larger structure, but these reactions could
still be of interest, you would have to judge.

>> [Parts of Original Message Edited/Deleted] <<

Sincerely

Pierre Allemand Ph.D.
Senior Account Manager

_____________________________Reply Separator_________________________________
Subject: Re: CCL:Reaction Pathway Program
Author:  chamot ([email-masked]) at unix,sh
Date:    7/16/97 3:28 PM

Hi Joe,

I haven't heard anything about it for a while, but I think you want the
program:

o LHASA (Logic and Heuristics Applied to Synthetic Analysis) is a backward
chaining synthesis planning program which uses a database of specially coded
chemical reactions and definitions for strategic bonds to analyze potential
synthetic pathways for a molecule.  The target molecule is analyzed according
to the number of rules and likely synthetic pathways are produced for
examination. -- Alan Long (last contact I know of), Harvard University.

At the time, it seemed very systematic, and would develop a retrosynthetic tree
(basically, "unsynthesize" the compound), showing all precursors for all
reasonable reactions for however many reaction steps you cared to follow back.
You could control how focused it was by defining minimum expected yields, and
paring branches you didn't want it to follow, or you could let it go
unconstrained.

I don't know much about the following programs, from the list I keep on my web
site for reference, but you may be interested in one of them, too:

o CAMEO (Computer Assisted Mechanistic Evaluation of Organic Reactions) is a
forward chaining reaction prediction program.  Runs on VAX/VMS computer systems
and uses Tektronix graphics. -- William L. Jorgensen, Yale University.

o EROS (Elaboration of Reactions for Organic Synthesis) is a computer assisted
synthesis program developed by Gasteiger et.al. which uses a set of rules to
propose synthetic routes. -- Dr. Johann Gasteiger, Erlangen University.

o ORAC - (Organic Reaction Accessed by Computer) Computer Assisted Synthesis
-- Pergamon.

o SECS (Simulation and Evaluation of Chemical Synthesis) is a retro-synthesis
analysis program in much the same mold as LHASA and SYNCHEM.  The target
molecule is analyzed according to strategic reactions using a database of known
reactions as a guide for predicting single step transformations to simplified
compounds.  Several iterations of the procedure are required to develop a
synthesis plan. -- W. Todd Wipke, University of California, Santa Cruz.

o WODCA - Computer Assisted Synthesis -- J. Gasteiger.

EC
---
Ernest Chamot
Chamot Labs, Inc.
530 E. Hillside Rd.
Naperville, Illinois 60540
(630)637-1559
[email-masked]
http://www.chamotlabs.com/cl

_____________________________Reply Separator_________________________________
Subject: Re: CCL:Re: CCL:Reaction Pathway Program
Author:  chemistry-request ([email-masked]) at unix,mime
Date:    7/15/97 3:18 PM

Programs which perform exhaustive bond reordering for reaction prediction or
synthesis planning, or assemble reaction networks between speicified endpoints,
can do this.  Typically, these programs employ additional constraints to
prevent entering the outlandish domains, but these checks can be disabled :-),
and thus all reaction pathways generated.  Be warned: You quickly generate
truly enourmous numbers of pathways.  Example programs which could work in this
mode are EROS5 (Gasteiger) and IGOR/RAIN (Ugi).  For literature references and
an overview, see Angewandte Chemie, Int. Ed. 1995, 34, 2613-2633.

--
Dr. Wolf-D. Ihlenfeldt
Computer Chemistry Center, University of Erlangen-Nuernberg
Naegelsbachstrasse 25, D-91052 Erlangen (Germany)
Tel (+49)-(0)9131-85-6579  Fax (+49)-(0)9131-85-6566
---
The three proven methods for ultimate success and fame:
1) Nakanu nara koroshite shimae hototogisu
2) Nakanu nara nakasete miseyou hototogisu
3) Nakanu nara naku made matou hototogisu

_____________________________Reply Separator_________________________________
Subject: CCL:Re:CCL: Reaction Pathway Program
Author:  chemistry-request ([email-masked]) at unix,mime
Date:    7/16/97 4:09 AM

Douglas,

Pure and Appl. Chem. vol.62, 10, pp 1921 "Abstract- An interactive computer
program, CAMEO, has been developed to predict products of organic reactions
given the starting materials and conditions..."

At the beginning CAMEO was a reaction simulator, but is there a new module now
in CAMEO that " can suggest 'reasonable' synthetic routes to various types of
compounds and functionality"?

I don't know if they are all maintained and commercialized but a lots of
Computer Assisted Organic Synthesis (CAOS) programs that works in a
retrosynthetic way have been designed.  I suggest you to have a look at:

"Computer-assisted Solution of Chemical Problems - The historical Development
 and the Present State of the Art of a New discipline of Chemistry" by Ivar Ugi
 and al. in Angew. Chem. Int. Ed. Engl. 1993, 32, 201-227

It's a huge review on computer chemistry, but a good part of it deals with
CAOS.

Now if you want a quick answer on one of the commercial products, try
http://www.chem.leeds.ac.uk/LUK/

Hope it helps

Jean-Francois Marchaland

_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/
_/ Dr J.F. Marchaland           [email-masked]              _/
_/ ICAMS, School of Chemistry   UK: 0113 233 6567               _/
_/ University of Leeds          internat.: +44 113 233 6567     _/
_/ LS29JT LEEDS                 FAX: 6563                       _/
_/                                                              _/
_/ http://chem.leeds.ac.uk/ICAMS/people/jfm.html                _/
_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/

_____________________________Reply Separator_________________________________
Subject: Retrosynthesis analysis
Author:  jfm ([email-masked]) at unix,mime
Date:    7/17/97 12:36 PM

CAMEO does not do "retro-synthesis", but reaction simulation.

Besides you could add:

PASCOP: Gerard Kaufmann, University of Strasbourg
SYNCHEM: H. Gelernter U.S. Stony Brook
http://www.cs.sunysb.edu/~ors/Fall-1994/gelern-94.html
SECS: W.T. Wipke UC Santa-Cruz

regards

Jeff

_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/
_/ Dr J.F. Marchaland           [email-masked]              _/
_/ ICAMS, School of Chemistry   UK: 0113 233 6567               _/
_/ University of Leeds          internat.: +44 113 233 6567     _/
_/ LS29JT LEEDS                 FAX: 6563                       _/
_/                                                              _/
_/ http://chem.leeds.ac.uk/ICAMS/people/jfm.html                _/
_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/_/

_____________________________Reply Separator_________________________________
Subject: RE: CCL:SUMMARY - Reaction Pathway Programs
Author:  yvonne.c.martin ([email-masked]) at unix,mime
Date:    7/18/97 6:10 PM

There is also CESA from Peter Johnson @ Leeds.  ([email-masked])

>-- END Tue Jul 22 08:24:32 CDT 1997

-- 

:Joe
 [email-masked]
 (630) 961-7878  <SOCON 231 7878>

 +------------------------------------------------+
 | A man doesn't automatically get my respect.    |
 | He has to get down in the dirt and beg for it. |
 |                                  - Jack Handey |
 +------------------------------------------------+