TARGET-ORIENTED AND DIVERSITY-ORIENTED ORGANIC SYNTHESIS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 531

another standard where the chemistry will necessitate additional investigation. The
examples shown in this chapter have highlighted some of the most powerful reactions
used in DOS, including multicomponent reactions, pericyclic processes, and
ruthenium-catalyzed metathesis. Such reactions have been chosen for the high degree
of structural complexity that can be generated in a single step, associated with a high
level of stereochemical control. Moreover, remodeling a molecular skeleton can be
achieved effectively under very mild reaction conditions, often resulting in structures
that would otherwise require less appealing multistep syntheses. However, these
chemical processes suffer from the lack of catalysts that can favor the controlled
formation of alternative structures by overriding the selectivity imposed by the
substrate. The development of novel catalysts is an important challenge that requires
tremendous efforts and the attention of the most expert chemist. Finally, the art of
diversity-oriented synthesis has laid down the foundation for the discovery of
important molecular probes such as uretupamine and secramine used to perturb
and elucidate biological processes, as well as small molecule drugs such as gemmacin
as a novel class of antibiotics. Often, these probes retain molecular frameworks
reminiscent of natural products (e.g., secramine), but some others are the pure product
of a creative mind (e.g., uretupamine, gemmacin). The question is no longer “What
starting materials and synthetic sequences will lead me to this target?” but
rather “What interesting targets can I make from these starting materials?” [61]. In
a sense, natural product chemistry is more straightforward because the molecule has
already been designed by Nature alleviating the task of chemical design and also
more appealing because the chemist already knows that the structure is inherently
accessible. On the other hand, processing novel structures and identifying an
effective method to create them in a selective manner may be more adventurous.
Nevertheless, target-oriented and diversity-oriented organic syntheses benefit one
another and tend to achieve complementary goals. Natural productsmay be used as a
model to imagine and create libraries of structural analogues or completely
unrelated structures that lead to the implementation of novel chemical reactions
and catalysts. There is no doubt that DOS holds great promise with regard to the
discovery of both selective catalysts and novel biologically active compounds, since
the fundamental principles have been established and the scope has been defined.
Nonetheless, the dialogue between chemists and biologists will be crucial to
identifying relevant structures to synthesize and the appropriate screening assays
to develop.
ABBREVIATIONS
Ac, acetyl; aq, aqueous; Ar, aryl (substituted aromatic ring); Boc, t -butoxycarbonyl;
Bs, 4-bromobenzenesulfonyl; Bz, benzoyl; cat., catalyst; con, conrotatory; Cy,
cyclohexyl; DBU, 1,8-diazabicyclo[5.4.0]undec-7-ene; de, diastereomeric excess;
DEAD, diethyl azodicarboxylate; DIAD, diisopropyl azodicarboxylate; DIPC, bis
(2,6-diisopropylphenyl)carbodiimide; DIPEA, diisopropylethylamine; dis, disrota-
tory; DMAP, N , N -4-dimethylaminopyridine; DMF, N , N -dimethylformamide; dr,
diastereomeric ratio; EDC, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide; ee,