Cyclic depsipeptides (CDPs) are a family of cyclic peptide-related compounds, of which the
ring is mainly composed of amino- and hydroxy acid residues joined by amide and ester bonds (at least
one), leading to a wide diversity of fascinating chemical structures. They differ in both their ring structure
and their side chains, especially by the nature of the unusual and non-amino acid building blocks.
To date, however, there is no overall uniform chemical classification system available for CDPs and
naming of the diverse family members is done rather arbitrarily. Therefore, a broad evaluation of different
CDP structures is done, i.e., 1348 naturally occurring CDPs were included, and a straightforward
chemical classification system using apparent chemical characteristics is proposed in order to organize
the currently scattered CDP data. The overall validity of the classification approach is verified and the
compounds categorized in the same groups are considered to be structurally related. This evaluation also
revealed that traditionally formed CDP subfamilies, like the dolastatins, might be misleading from a
chemical point of view given the structural differences in this subfamily. This up-to-date CDP overview
enables peptide and natural product scientists to study the wide diversity in CDP structures, their chemical
interrelationships and identification of existing and newly found CDPs. Together with the available
information on the species producing these CDPs and their reported biological activities, this paper provides
a useful tool to gain new insights into this diverse group of peptides.