Linker units hydrazones

Reflecting the high impact that using hydrazones as chiral auxiliaries has had on asymmetric synthesis, recent efforts have explored the use of chiral linker units in approaches toward solid-phase asymmetric synthesis (SPAS). Efforts thus far have concentrated on supported analogues of the chiral SAMP analogues (e.g.. Table 1.9, Entry 9), and while the reported ee s are acceptable, they have yet to match results obtained in the analogous solution-phase reactions. 

A recent trend is to design polymers with multiple functions including cationic units to bind nucleic acids as well as pH-sensitive carboxylic acids for endosomal dismption. Using a block copolymer architecture, comb-like polymers with cationic grafts were extended from aspartic acid units via a hydrazone linkers.The second block was composed of... 

MED-2220, which are attached to antibodies with lysines thiolated by 2-IT (2-iminothiolane, Trout s reagent Figure 7.12). The phenol in the open form of the CBI alkylating unit is protected as a carbamate of tV-methyl piperazine, which likely increases stability and adds solubility. The cyclopropane precursor contains a bromine instead of chlorine for undisclosed reasons. The linker is attached via an acyl hydrazone similar to the AcBut linker in several cali-cheamicin conjugates. The linker contains a short PEG unit that would also likely improve solubility. 

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