Bioresponsive polymeric nanoparticles have been extensively pursued for the development of tumor-targeted drug delivery. A novel redox-sensitive biodegradable polymer with "trimethyl-locked" benzoquinone was synthesized for the preparation of paclitaxel-incorporated nanoparticles. The synthesized redox-sensitive nanoparticles released paclitaxel in response to chemically triggered reduction.

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High exo-facial selectivity was observed in the selective monohydrolysis of a series of near-symmetric diesters that possess an exo-ester group and an endo-ester group attached on a norbornane or norbornene skeleton. The selectivities were found to be clear-cut, although the reaction center in these reactions is one covalent bond distant from the norbornane or norbornene ring, where the difference of the environment between the exo face and endo face is therefore expected to be negligible. The effect of the co-solvent we studied earlier for the selective monohydrolysis reaction was also confirmed and contributed to improvement of the yields of the half-esters.

Half-esters of malonic acid such as monomethyl malonate and monoethyl malonate are very important building blocks. They have been frequently applied to synthesis of a variety of significant pharmaceuticals and natural products. [2][3][4][5][6][7][8][9][10][11][12][13] However, their commercial availability is still limited and quite expensive, and they are more commonly available as the corresponding potassium salts. In particular, monomethyl malonate became commercially available only last year, but is expensive, or the purities are typically less than 99%, such as 96%. Therefore, development of a more efficient synthetic method for monoalkyl malonates on a large scale is essential.One method for preparation of half-esters is monosaponification of symmetric diesters, but successful distinction of the two identical ester groups remains challenging. In fact, monosaponification typically produces a dirty mixture of the starting diester, the corresponding halfester, and the diacid, even with the use of one equivalent of a base. In particular, the synthesis of half-esters of malonic acid is still difficult especially on a large scale, because of potential decarboxylation. Only a limited number of examples of monosaponification of dimethyl or diethyl malonate have been reported, [14][15][16] but they require a long time and more than one step. Some modified methods are reported applying Meldrum's acid, 17,18) but Meldrum's acid is costly and not suitable for large-scale production of monoalkyl malononate. The enzymatic monohydrolysis of dialkyl malonates reported utilizes an enzyme not commercially available. 19) Other methods by carbalkoxylation of malonic acid are also reported, but the yields are rather modest. 20)Herein we describe a large-scale synthesis of monomethyl malonate and monoethyl malonate applying the selective monohydrolysis of symmetric diesters we reported before. Earlier, we reported a selective monohydrolysis that enables a series of symmetric diesters with the use of an aqueous NaOH or KOH and a co-solvent such as tetrahydrofuran (THF) or CH 3 CN at 0°C (Chart 1).21) This reaction is practical, mild, and environmentally benign, and has been of interest in process chemistry, exhibiting the potential of scaling up. The selectivity of this reaction was initially found to be particularly high for cyclic 1,2-diesters with the two ester groups in close proximity, even with the use of almost 2 equivalents (or greater) of the base, producing the corresponding half-esters in near-quantitative yields. We reasoned that electrostatic attractive interaction between the two closely located carbonyl groups may play a role in this high selectivity. We recently modified the conditions of this reaction and applied them to monohydrolysis of a series of dialkyl malonates and their derivatives on the scale of 1.2 mmol. 22) They show that the yields are around 80% to near quantitative. Here we examined the possibility of scaling up this reaction, focusing on monomethyl malonate and monoethyl malonate, which are among...

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