Bodipy-Based Fluorescent Analog of the Molecular Vaccine Adjuvants Sulfavants

Recently, we described synthetic sulfolipids named Sulfavants (1-3) as a novel class of molecular vaccine adjuvants based on the sulfoquinovosyl-diacylglycerol skeleton.[1,2] These compounds induce maturation of human DCs by the up-regulation of phenotypic markers.[1,3] In particular, Sulfavant A (1), the prototype of this class of molecules, was proved to boost immune protection and to act as an adjuvant in mice in an experimental model of cancer vaccine against a murine B16F10 melanoma cell line, that is widely used for therapeutic evaluation. 

Therefore, the Sulfavants are ideal candidates to be used as vaccine adjuvants in relation to their efficiency properties accompanied by a low possibility of giving side effects.[1] Crucial steps for the pharmacological development of this class of adjuvants are certainly the elucidation of the biological mechanisms, the interactions between these compounds and their cellular targets, the monitoring of their metabolism and the mapping bio-distribution in cells and in vivo. With these purposes, the preparation of fluorescent analogs of Sulfavants is an essential factor for future biological studies. In this regard, we planned a chemical strategy for the synthesis of a Sulfavant fluorescent analog linked to the 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene moiety (BODIPY) named Sulfavant R-BODIPY (4). 

The preparation of the Sulfavant R-BODIPY (4) dye was achieved by a versatile diastereoselective synthesis based on the trichloroacetimidate method which opens a straightforward access to a wide class of fluorescent sulfolipids derivatives, essential tools for achieving a better comprehension of the biological mechanisms at the base of adjuvant activity of this class of molecules.