RE: [chemweb] ORGLIST: SMILES List of Cheap Starting Materials? (fwdfrom yadavm@scripps.edu) (fwd from rscoffin@cambridgesoft.com)

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From: Eugen Leitl (eugen$##$leitl.org)
Date: Mon Dec 06 2004 - 07:24:08 EST


----- Forwarded message from Rob Scoffin <rscoffin$##$cambridgesoft.com> -----

From: "Rob Scoffin" <rscoffin$##$cambridgesoft.com>
Date: Mon, 6 Dec 2004 11:37:20 -0000
To: "'Eugen Leitl'" <eugen$##$leitl.org>, <yadavm$##$scripps.edu>
Subject: RE: [chemweb] ORGLIST: SMILES List of Cheap Starting Materials? (fwdfrom yadavm$##$scripps.edu)
Reply-To: <rscoffin$##$cambridgesoft.com>
Organization: CambridgeSoft Corporation
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Maneesh,

Interesting idea!

The best source of cheap chemicals would either be to use the "High
Production Volume" chemicals or HPV list - see
http://www.epa.gov/opptintr/chemrtk/hpvchmlt.htm for example.

Alternatively search in the CambridgeSoft ChemACX database for compounds and
calculate a cost per Kg based on the manufacturers pricing tables - this
requires a little bit of work in MS Access to get the normalised pricing.

The CambridgeSoft ChemFinder desktop database or Oracle Chemistry Cartridge,
in conjunction with ChemDraw, can be used to develop automatic reaction
analysis tools - we support automatic mapping using an algorithm based on
"minimum chemical distance" i.e. minimise the number of bonds made/broken in
the reaction to generate a sensible automatic map.

Putting the compounds and reactions together could be done using a CombiChem
toolkit.

Be aware that the combinatorics of taking say 100 cheap compounds and then
reacting them in 5 steps where each step can use one of 20 reactions would
give you more than 100 * 20^5 == 320 x 10^6 possible molecules !

Rob
===

Dr. Robert Scoffin
Executive Director, European Operations

CambridgeSoft t: +44 (0)1223 358080
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> -----Original Message-----
> From: chemweb-bounces$##$imperial.ac.uk
> [mailto:chemweb-bounces$##$imperial.ac.uk] On Behalf Of Eugen Leitl
> Sent: 06 December 2004 11:13
> To: chemweb$##$imperial.ac.uk
> Subject: [chemweb] ORGLIST: SMILES List of Cheap Starting
> Materials? (fwdfrom yadavm$##$scripps.edu)
>
> ----- Forwarded message from Maneesh Yadav <yadavm$##$scripps.edu> -----
>
> From: "Maneesh Yadav" <yadavm$##$scripps.edu>
> Date: Sat, 4 Dec 2004 20:48:39 -0800
> To: <everybody$##$orglist.net>
> Subject: ORGLIST: SMILES List of Cheap Starting Materials?
>
> Dear ORGLIST/CHEMINF readers,
>
> I recently found myself synthesizing a simple molecule which
> can be used as a photoacid, namely,
> 4-formyl-6-methoxy-3-nitrophenoxyacetic acid, accessible in
> two simple steps from vanillin*1.
>
> I am always surprised when I can make such interesting and
> useful molecules so darn easily and cheaply, I am interested
> in a method where I could produce an exhaustive list of all
> such molecules, i.e. every small molecule that is
> synthetically accessible in under five steps from the pool of
> cheap starting materials, using only "easy" reactions.
>
> I have a few questions, and wanted to subject myself to some
> critisism/comment, I try to detail my idea below.
>
> What Are Cheap Starting Materials?
> Naturally the definition of "cheap" depends on supply and
> demand (which also drives discovery of new chemical
> knowledge); but I think a good criteria would be anything I
> could buy on the gram scale for under $100. This list would
> include things like vanillin, citronellal, carvone,
> industrial dyes, natural amino acids, common acids/bases
> (sulphuric acid, sodium hydroxide), cyclopentadiene, benzene,
> acetone, ethanol, methanol etc. I think you get the idea.
>
> It is surprisingly difficult to construct such a list of
> starting materials (in the form of a list of SMILES strings).
> Aldrich does not seem to have the ability to query by price
> in their internal database system (that is what they tell me
> at least). If anyone can think of a better way to do this
> than burning me eyes out in front of Chemdraw and an Aldrich
> catalog for a few weekends, please let me know. I think 1000
> compounds would be a good place to start. I'd put up a
> wiki/database system linked to suppliers if anyone else would
> find value in such a list.
>
> What Are Easy Reactions?
> Sharpless et. al define the notion of "Click Chemistry"*2 as
> a set of reactions which been demonstrated to posses very
> favorable exergonicities in multiple contexts (among a few
> other qualifiers). The basic idea is that the these reactions
> tend to "just work" and include reactions like Diels-Alder,
> acetylene-azide dipolar cycloaddition and epoxide
> formation/opening. While I wouldn't necessarily limit myself
> strictly to "click" reactions, the idea is to limit the
> number of reactions that will be applied to good easy ones.
>
> I haven't run across an elegant way to specify chemical
> reactions in detail. I am collaborating with Gabriel
> Valiente, who has implemented a basic reaction facility to
> PerlMol. He has also wondered if there is some sort of
> algebra by which we can make smaller descriptions, specify
> branched outcomes etc. that take advantage of the fact the
> most reactions have very "natural" atom mappings, as opposed
> to the completely explicit mappings we are using right now.
> I know that Sertanty Inc. has something neat in the works,
> but given it is commercial, I don't have too much of an idea.
>
>
>
> What Good Would It Be?
>
> The final result would be to iteratively apply our easy
> reactions to our cheap starting materials (filtering
> conformationally implausible beasts, at each step) to
> generate a list of compounds and plausible synthetic routes
> to them. It'd be interesting to ask about the comparative
> molecular diversity of the final list, and statistical
> information about the synthetic routes.
>
>
>
> Again please let me know about any ideas about:
>
> a)How to get a large list of cheap compounds in the form of
> SMILES strings.
> b)A better way of specifying chemical reactions, rather than
> explicit atom mapping (software etc.).
>
>
> *1
> Biochim Biophys Acta. 1987 Dec 11;905(2):409-16.
> Proton concentration jumps and generation of transmembrane
> pH-gradients by photolysis of
> 4-formyl-6-methoxy-3-nitrophenoxyacetic acid.
> Janko K, Reichert J.
>
> *2
> Angew. Chem. Int. Ed. 2001, 40,2004--2021
>
>
>
>
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> ----- End forwarded message -----
> --
> Eugen* Leitl leitl
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----- End forwarded message -----

-- 
Eugen* Leitl leitl
______________________________________________________________
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