Biomedical Engineering Reference
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more convenient solution was found based on a Ugi reaction followed by a
cyclization [51] .
One of the required starting materials for an Ugi-related synthesis strategy
to many of the members of the diketopiperazine library was the compound
known as DOPAL (3,4-dihydroxyphenylacetaldehyde). This compound could
not be purchased and the synthesis of DOPAL therefore became a primary
synthetic focus. A question arose as to whether the presence of a phenolic
group would interfere in the Ugi reaction [52]. This concern was greatly dimin-
ished by a contribution from ChemRefer, where an article reported that an
electron-withdrawing group on the aromatic ring is necessary for the phenol
to participate in the Ugi reaction [53]. Feedback from an expert in the fi eld
supported this assessment [54].
Synthetic methods to prepare DOPAL were discussed on the blog [55] and
the synthesis was fi nally solved in October 2006 [56]. Progress was slowed by
errors in the literature. However, a report [57] detailing these errors and
linking to the “failed experiments” that uncovered their discovery demon-
strated that ONS could be useful for providing more transparency in science
and saving time in the future for anyone attempting to repeat the synthesis.
Unfortunately, DOPAL and similar aldehydes proved to be too susceptible
to side reactions, and other more stable compounds were used to try to under-
stand the behavior and kinetics of the Ugi reaction fi rst [58, 59]. Research work
often has to deviate from initial plans due to unexpected problems. However,
the nature of those problems is not usually communicated in suffi cient detail
(or at all) via traditional channels. In a sense, making the details of these
problems easily indexed on major search engines is a type of collaboration
with future researchers who may run into similar problems and benefi t from
the details provided.
25.3.4 Cheminformatics: Collaborations Between
Chemists and Programmers
The representation, manipulation, and communication of chemical informa-
tion in an open-science environment is not a trivial challenge. One of the earli-
est cheminformatics tasks consisted of converting the format of the fi rst
malaria virtual library to one that was easier to share publicly. One of the
Find-A-Drug volunteers contributed by providing the library as a simplifi ed
molecular input line entry specifi cation (SMILES) list [60], a text-based format
consisting of a string of characters that can be easily manipulated in spread-
sheets [61]. The discovery of open-source software such as Open Babel [62]
would also prove to be critical for the cheminformatics needs of the project.
An ecosystem of open science related to cheminformatics evolved over time.
Projects with overlapping objectives naturally interlinked at a convenient
level. For example, the UsefulChem project had a presence on The Synaptic
Leap for the purpose of fi nding collaborators [63], including a suggestion for
a free docking program [64]. Several key individuals with overlapping interests
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