Current Organic Chemistry, 2000, 4, 121-138
121
Synthetic Approaches to the Eudistomin Marine Alkaloids
J. McNulty*a and I.W.J. Still*b
a Department of Chemistry, Brock University, St. Catharines, Ontario, Canada L2S 3A1
bDepartment of Chemistry, University of Toronto at Mississauga, Mississauga, Ontario, Canada L5L 1C6
Abstract: The isolation, structure determination and biological evaluation of the eudistomin
alkaloids, isolated mainly from marine tunicates of the genus Eudistoma, is described. The
compounds are placed in a well defined unique structural class based upon biogenic
considerations. The methods which have been employed towards total synthesis of these
metabolites are reviewed in detail.
Introduction
source of nitrogenous secondary metabolites often of
unique structural types and endowed with biological
properties of interest [1]. In 1984, Rinehart and co-
workers reported the isolation of a new family of 17
compounds from the Caribbean tunicate Eudistoma
olivaceum [4-6] which were named eudistomins A
through Q. This work was followed by a profusion of
isolation studies from related Eudistoma sp. by several
groups around the world, resulting in the addition of a
further 19 compounds to the series [7-16]. While a
great number of structurally diverse compounds have
been isolated from tunicates [1], it is convenient to
group the eudistomin-eudistomidin class together on
biogenic considerations. Structural analysis reveals the
eudistomins to be biosynthetically derived from a
tryptophan
residue, often
ring-A
functionalized,
condensed with a second amino acid such as a
cysteinyl, glutamic acid or prolinyl, phenylalaninyl,
isoleucinyl, or C-1 unsubstituted (possibly glycine
derived) residue, Scheme 1. Subsequent metabolic
processes,
including oxidation,
dehydrogenation,
decarboxylation or methylation, may
then be
envisioned to give rise to all of the known eudistomin
structures. The only exception to this general pattern
appears to be the alkaloid named eudistomin U and
related analogs, isolated fr