Page 19 - Advanced Organic Chemistry Part B - Reactions & Synthesis

xx out a 39-step synthesis. The early stages were done on a kilogram scale and the entire
effort provided 60 grams of the final product for preliminary clinical evaluation.
Introduction
CH 3 CH 3 CH 3 24
8
HO 15 17
9 CH
H 3 21
O O CH OH OCONH 2
1 5 CH 3 11 3
HO
CH 3 CH 3
OH (+)–Discodermolide

There is no synthetic path that is uniquely “correct,” but there may be factors
that recommend particular pathways. The design of a synthesis involves applying
one’s knowledge about reactions. Is the reaction applicable to the particular steric
and electronic environment under consideration? Is the reaction compatible with other
functional groups and structures that are present elsewhere in the molecule? Will the
reaction meet the regio- and stereochemical requirements that apply? Chemists rely
on mechanistic considerations and the precedent of related reactions to make these
judgments. Other considerations may come into play as well, such as availability and/or
cost of starting materials, and safety and environmental issues might make one reaction
preferable to another. These are critical concerns in synthesis on a production scale.
Certain types of molecules, especially polypeptides and polynucleotides, lend
themselves to synthesis on solid supports. In such syntheses, the starting material is
attached to a small particle (bead) or a surface and the molecule remains attached
during the course of the synthetic sequence. Solid phase synthesis also plays a key role
in creation of combinatorial libraries, that is, collections of many molecules synthesized
by a sequence of reactions in which the subunits are systematically varied to create a
range of structures (molecular diversity).
There is a vast amount of knowledge about reactions and how to use them in
synthesis. The primary source for this information is the published chemical liter-
ature that is available in numerous journals, and additional information can be found
in patents, theses and dissertations, and technical reports of industrial and govern-
mental organizations. There are several means of gaining access to information about
specific reactions. The series Organic Syntheses provides examples of specific trans-
formations with detailed experimental procedures. Another series, Organic Reactions,
provides fundamental information about the scope and mechanism as well as compre-
hensive literature references to many examples of a specific reaction type. Various
review journals, including Accounts of Chemical Research and Chemical Reviews,
provide overviews of particular reactions. A traditional system of organization is based
on named reactions. Many important reactions bear well-recognized names of the
chemists involved in their discovery or development. Other names such as dehydration,
epoxidation, enolate alkylation, etc., are succinct descriptions of the structural changes
associated with the reaction. This vocabulary is an important tool for accessing infor-
mation about organic reactions. There are large computerized databases of organic
reactions, most notably those of Chemical Abstracts and Beilstein. Chemical structures
can be uniquely described and these databases can be searched for complete or partial
structures. Systematic ways of searching for reactions are also incorporated into the
databases. Another database, Science Citation Index, allows search for subsequent
citations of published work.