ABSTRACT
Three QS-21-based vaccine adjuvant candidates with a terminal-functionalized side chain incorporated in the west wing trisaccharide have been synthesized. The terminal polar functional group serves to increase the solubility of these analogues in water. Two of the synthetic analogues have been shown to have adjuvant activity comparable to that of GPI-0100. The stand-alone adjuvant activity of the new synthetic analogues again confirmed that it is a feasible way to develop new saponin-based vaccine adjuvants through derivatizing at the west wing branched trisaccharide domain. Inclusion of an additional polar functional group such as a carboxyl group (as in 3x) or a monosaccharide (as in 4x and 5x) is sufficient to increase the water solubility of the corresponding synthetic analogues to a level comparable to that of GPI-0100 and suitable for immunological studies and clinical application. The structure of the incorporated side chain has a significant impact on the adjuvant activity in terms of the magnitude and nature of the host's responses.
Subject(s)
Adjuvants, Immunologic/chemical synthesis , Saponins/chemistry , Trisaccharides/chemistry , Adjuvants, Immunologic/chemistry , Adjuvants, Immunologic/pharmacology , Animals , Antibody Formation/drug effects , Carbohydrate Sequence , Carbon-13 Magnetic Resonance Spectroscopy , Enzyme-Linked Immunosorbent Assay , Female , Mass Spectrometry/methods , Mice , Mice, Inbred BALB C , Proton Magnetic Resonance SpectroscopyABSTRACT
Two structurally simple photolabile protecting groups for releasing 1,2- and 1,3-diols have been developed. The diols can be protected in high yields and released from their corresponding acetals with high chemical efficiency.
ABSTRACT
The 3-(diethylamino)benzyl (DEABn) group has been studied for releasing primary, secondary, and tertiary amines by direct photochemical breaking of the benzylic C-N bond. While photochemical release of primary and secondary amines provides high yields in methanol, release of tertiary amines in MeCN/water can improve yields and reduce the undesired dealkylation side reaction.
ABSTRACT
Structurally simple benzyl-type photolabile protecting groups (PPGs) have been developed to release alcohols and carboxylic acids. Release of two substrates from one PPG chromophore has also been accomplished.
ABSTRACT
The HKR of racemic anti- or syn-3-substituted epoxy esters catalyzed by a Co(III)salen complex provides ready access to the corresponding enantioenriched 3,4-disubstituted γ-butyrolactones and 3-substituted epoxy esters. This strategy has been successfully employed in the formal synthesis of biologically active 3,4-disubstituted piperidine derivatives, (-)-paroxetine and Ro 67-8867 and a natural product, (+)-eldanolide.
