Self-immolative

It may be of interest to note that the stereospecific transformation shown in equation 15 has been cited as the first reported observation of an 1 - 3 chirality transfer. It is evident that on rearrangement of optically active 6d to 7d, the chiral center at C-a is eliminated and a new one created at C-y. The term self-immolative asymmetric synthesis has also been used to describe syntheses of this kind. As pointed out by Hoffmann , quantitative 1 - 3 chirality transfer will follow from the suprafacial - course of rearrangement, provided the reactant has a uniform configuration at the j8, y-double bond. This stereochemical prediction has also been confirmed by the results obtained in several other [2,3]sigmatropic rearrangements, subsequently reported " . 

FIGURE 5.42 Chemical structures of first-generation (42) and second-generation (43) self-immolative, receiver-amplifier dendritic molecules with an enzymatic trigger (blue), cleaved by PGA and 6-aminoquinoline (red) reporter groups. 

SELF-IMMOLATIVE DENDRIMERS BASED ON QUINONE METHIDES... 

FIGURE 5.1 Graphical structure of a tripartite prodrug with self-immolative linker. (See the color version of this figure in Color Plates section.)... 

FIGURE 5.3 Disassembly mechanism of a self-immolative AB3 dendritic adaptor. 

FIGURE 5.4 Disassembly mechanism of first-generation self-immolative dendron. 

FIGURE 5.5 Chemical structures of first- and second-generation self-immolative dendrons. 

ELIMINATION-BASED AB3 SELF-IMMOLATIVE DENDRITIC AMPLIFIER... 

FIGURE 5.8 Disassembly mechanism of AB3 self-immolative dendritic molecule 13. 

FIGURE 5.10 Chemical structures of AB3 self-immolative dendritic molecules with tryptophan tail units and a trigger that is activated by PGA. 

FIGURE 5.16 AB3 self-immolative dendritic system with diphenylalanine end units and a trigger designed for activation by PGA. 

FIGURE 5.21 Molecular structure of a single-triggered AB6 self-immolative dendritic... 

FIGURE 5.22 Disassembly mechanism of AB6 self-immolative dendron 27. 

Molecular structure of a self-immolative AB6 dendron with aminomethyl-pyrene reporter units and a Boc protecting group as a trigger. 

We also wanted to evaluate the disassembly of our dendritic system under physiological conditions. Thus, we synthesized a self-immolative AB6 dendron 32 with water-soluble tryptophan tail units and a phenylacetamide head as a trigger (Fig. 5.26) to evaluate disassembly in aqueous conditions. The phenylacetamide is selectively cleaved by the bacterial enzyme penicillin G amidase (PGA). The trigger was designed to disassemble through azaquinone methide rearrangement and cyclic dimethylurea elimination to release a phenol intermediate that will undergo six quinone methide elimination reactions to release the tryptophan tail units. 

ENZYMATIC ACTIVATION OF SECOND-GENERATION SELF-IMMOLATIVE DENDRIMERS... 

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