enamine catalysis, tandem iminium-enamine catalysis, and trienamine catalysis
[48a]. Furthermore, the introduction of chirality into the rotaxane catalyst could be
exploited in conjugate addition reactions giving improved enantioselectivities compared to non-interlocked catalysts [48d]. All these elegant rotaxane-type catalysts
provide a significant strategy for the construction of artificial switchable catalysts,
advancing rotaxanes toward functional smart catalysis.
11.3.3 Artificial Molecular Production Line
The performance of biological machines in crucial biological tasks within a complex
living organism inspired chemists to mimic this evolved biological machinery by
synthetic small molecules [32, 49]. Walking protein machines, called myosin,
kinesin, and dynein, are capable of “walking motion” powered by chemical energy
(the hydrolysis of adenosine triphosphate), performing like someone stepping forward with two feet. There have been reports on successful examples of DNA-based
molecular walkers that can move gold NPs or mediate multistep synthesis [50]. However, to build purely synthetic molecular walkers based on small molecules remained
a challenge until recently, when the group of Leigh designed and constructed the first
synthetic small-molecule walker using the Schiff base and disulfide dynamic covalent chemistry [32a]. Employing the versatile strategy of dynamic covalent bonding,
Leigh and co-workers also reported a synthetic small-molecule walker that accompanied with decreasing fluorescence change [32c]. More recently, the same group
reported a more advanced, completely synthetic small-molecule machine, involving
a robotic arm that could pick up, transport, and release molecular cargo [32f].
Rotaxanes can also perform as small-molecule walkers, and even as artificial
molecular production lines when the macrocycle moiety is walking along the thread,
which has been realized by Leigh and co-workers [51]. As shown in Fig. 7, [2]
rotaxane 23 consists of a sterically bulk stopper at one of the ends, a macrocycle
moiety, and a thread bearing three amino acid units in a specific order. In its initial
state, rotaxane 23 is stable due to the protecting groups present in the amino acids
and thiol group. The molecular production line does not work until the acidcatalyzed cleavage of the Boc and trityl protecting groups, in the presence of
CF 3 COOH. Upon exposure of the free primary amines and the thiol group, the
molecular walker was activated. Firstly, the thiolate catalyst was activated upon
deprotonation of the thiol by N, N-diisopropylethylamine, and then the first transacylation reaction (O-S acyl transfer) occurred between the thiolate group and the
first amino acid phenolate ester building block. The formed phenylalanine thioester
could further react and transfer the amino acid to the end of the growing peptide
chain and regenerate the catalytic thiol group through a 1,11-S, N acyl transfer
process. The first step of the molecular walker was finished, and then through
sequential transacylation reactions, amino acid transfers, and thiolate regenerations,
the macrocycle walker unit was able to pick up the amino acids from the track by
moving along the thread. Ultimately, the system was yielding a non-interlocked
thread and a macrocycle containing a peptide chain with four amino acids. Finally,
11 Functional Rotaxanes
291
[48a]. Furthermore, the introduction of chirality into the rotaxane catalyst could be
exploited in conjugate addition reactions giving improved enantioselectivities compared to non-interlocked catalysts [48d]. All these elegant rotaxane-type catalysts
provide a significant strategy for the construction of artificial switchable catalysts,
advancing rotaxanes toward functional smart catalysis.
11.3.3 Artificial Molecular Production Line
The performance of biological machines in crucial biological tasks within a complex
living organism inspired chemists to mimic this evolved biological machinery by
synthetic small molecules [32, 49]. Walking protein machines, called myosin,
kinesin, and dynein, are capable of “walking motion” powered by chemical energy
(the hydrolysis of adenosine triphosphate), performing like someone stepping forward with two feet. There have been reports on successful examples of DNA-based
molecular walkers that can move gold NPs or mediate multistep synthesis [50]. However, to build purely synthetic molecular walkers based on small molecules remained
a challenge until recently, when the group of Leigh designed and constructed the first
synthetic small-molecule walker using the Schiff base and disulfide dynamic covalent chemistry [32a]. Employing the versatile strategy of dynamic covalent bonding,
Leigh and co-workers also reported a synthetic small-molecule walker that accompanied with decreasing fluorescence change [32c]. More recently, the same group
reported a more advanced, completely synthetic small-molecule machine, involving
a robotic arm that could pick up, transport, and release molecular cargo [32f].
Rotaxanes can also perform as small-molecule walkers, and even as artificial
molecular production lines when the macrocycle moiety is walking along the thread,
which has been realized by Leigh and co-workers [51]. As shown in Fig. 7, [2]
rotaxane 23 consists of a sterically bulk stopper at one of the ends, a macrocycle
moiety, and a thread bearing three amino acid units in a specific order. In its initial
state, rotaxane 23 is stable due to the protecting groups present in the amino acids
and thiol group. The molecular production line does not work until the acidcatalyzed cleavage of the Boc and trityl protecting groups, in the presence of
CF 3 COOH. Upon exposure of the free primary amines and the thiol group, the
molecular walker was activated. Firstly, the thiolate catalyst was activated upon
deprotonation of the thiol by N, N-diisopropylethylamine, and then the first transacylation reaction (O-S acyl transfer) occurred between the thiolate group and the
first amino acid phenolate ester building block. The formed phenylalanine thioester
could further react and transfer the amino acid to the end of the growing peptide
chain and regenerate the catalytic thiol group through a 1,11-S, N acyl transfer
process. The first step of the molecular walker was finished, and then through
sequential transacylation reactions, amino acid transfers, and thiolate regenerations,
the macrocycle walker unit was able to pick up the amino acids from the track by
moving along the thread. Ultimately, the system was yielding a non-interlocked
thread and a macrocycle containing a peptide chain with four amino acids. Finally,
11 Functional Rotaxanes
291