I. Gonzalez et al., SYNTHESIS OF DERIVATIVES OF (2S,4S)-4-HYDROXY-2,5-DIMETHYL-3-OXOHEXANOIC ACID, A CONSTITUENT OF THE DIDEMNINS, Journal of the Chemical Society. Perkin transactions. I, (12), 1996, pp. 1427-1433
The syntheses of the two protected derivatives 7 and 16 of (2S,4S)-4-h
ydroxy-2, 5-dimethyl-3-oxohexanoic acid, a constituent of the didemnin
family of antineoplastic macrocyclic depsipeptides are described, The
preparation of 7 was carried out by modification of a previously repo
rted synthetic route whereas the use of derivative 16 represents a nov
el approach to the management of this sub-unit, Removal of the carboxy
protecting groups from 7 or 16, followed by amide bond formation with
derivatives of(S)-leucine, and oxidation in the cases of compounds de
riving from 16, generates the diastereoisomeric intermediates 11, 22 a
nd 23, In each of these either of the protecting groups can be removed
in the presence of the other, allowing them to be elaborated further
at either terminus, Previous work indicates that diastereoisomeric mix
tures of such intermediates can, in principle, be used to obtain optic
ally pure didemnins.