Analogs of viscosin and their uses

DETAILED DESCRIPTION OF THE INVENTION Viscosin is a peptide lactone composed of alternating D and L amino acids with a .
beta.
-D-hydroxydecanoyl dipeptide side chain.
This peptide has antibacterial, antiviral and antitrypanosomal activity against Tyrpanosoma cruzi, the pathogen involved in the South American Chagas' disease.
The synthesis by solid phase methods utilizing an acid sensitive resin and a combination of Fmoc/Boc amino protection is described in Example 1.
In an effort to develop antichagasic agents based on viscosin, a series of analogs were prepared which were synthetically more accessible.
One aspect of this invention involves alteration of the peptide side chain and ring junction.
Side chain analogs consist of a variety of linear alkyl amides while modifications in the ring junction involve replacing the D-allo-Thr with D-Thr.
Synthesis of these analogs is based on those techniques used to prepare viscosin itself, and rely on the novel use of activated esters of pentafluorophenol for the coupling of unprotected hydroxyl-bearing amino acids.
A second aspect of this invention addresses the rate of ion transport in viscosin's anticruzi activity and involves replacement of the peptide lactone ring with a crown ether.
In general, any crown ether that has ionophore properties may be substituted for the peptide lactone ring of viscosin.
Preferable crown ethers include benzo-15-crown-5 polyether, dibenzo-18-crown-6 polyether, dibenzo-24-crown-8 polyether, 2-hydroxymethyl-12-crown-4, 2-hydroxymethyl-15-crown-5 polyether, and 2-hydroxymethyl-18-crown-6 polyether.
A most preferable crown ether is benzo-15-crown-5 polyether.
These analogs may further differ from each other in the side chain R which are long chain alkylamides or simple peptides.
The viscosin analogs comprising crown ethers may be prepared according to the general methods of synthesis set forth in the examples section of the application.
For example, where the crown ether is fused to a benzene ring, it is possible to nitrate the ring with nitric acid, followed by reduction to give the amine followed by the condensation thereof with an appropriate side chain precursor to give the viscosin derivative