The invention discloses a preparation method of monofunctionalized nonlinear
polyethylene glycol. The monofunctionalized nonlinear
polyethylene glycol has a nonlinear multivalent group U, one side ofthe nonlinear multivalent group is connected with a single functional
end group, and the other side of the nonlinear multivalent group is connected with at least two linear
polyethylene glycol chains.The preparation method includes the steps, first, a low molecular weight intermediate IM1 is obtained first, and the single functional
end group or a microvariant form is introduced; and the step only refers to an
organic reaction between low molecular weight reagents, the
controllability is good, the structure can be precisely controlled, selectable segregation patterns are diverse, and a high-purity intermediate can be obtained; and second, then a
polyethylene glycol component is introduced, and the monofunctional nonlinear
polyethylene glycol with a high substitution rate can be obtained directly or by simple
chemical modification of a terminal. When the monofunctionalized nonlinear
polyethylene glycol continues functionalized modification or is used as a reaction
raw material to construct a multistage branched
nonlinear structure, the reaction steric hindrance is small, and a relatively high substitution rate or a relatively high
grafting rate can also be obtained.