This review focuses on utilization of the excited state meta effect (ESME) in the development of photolabile protecting groups (PPGs). Structurally simple ESME-based PPGs for release of various functional groups (such as carbonyl, hydroxyl, carboxyl, amino and thiol groups) are discussed.Examples that demonstrate the appealing advantages of these new PPGs are provided, including their efficient release of "poor" leaving groups such as hydroxyl or amino group directly instead of in their respective carbonate or carbamate form. Applications of these PPGs in synthesis, release of biologically important molecules, materials science and biomedical engineering are also described.

VSA-2 is a recently developed semisynthetic saponin immunostimulant. It is prepared by incorporating a terminal-functionalized side chain to the branched trisaccharide domain at the C3 position of Momordica saponin II (MS II) isolated from the seeds of perennial Momordica cochinchinensis Spreng. Direct comparison of VSA-2 and the clinically proven saponin adjuvant QS-21 shows that VSA-2 is comparable to QS-21 in enhancing humoral and cellular immune responses. Structure− activity relationship studies show that structural changes in the side chain have a significant impact on saponins' adjuvant activity. However, with the VSA-2 molecular framework intact, the new VSA-2 analogues with various substitution(s) at the terminal benzyl group of the side chain retain the ability of potentiating antigen-specific humoral and cellular responses.