Cytosine-type bridged nucleoside amidite crystals and method for producing same
A cytosine-type bridged nucleoside amidite crystal represented by the following structural formula: in which R 1 and R 2 each represents a substituent, and R 3 represents a protecting group.
1 . A cytosine-type bridged nucleoside amidite crystal represented by the following structural formula:
in which R 1 is a benzamido group, R 2 is a methyl group, and R 3 is a dimethoxytrityl group, and the cytosine-type bridged nucleoside amidite crystal has any one of characteristic peak patterns of crystal A, crystal B, and crystal C shown below, as a diffraction angle (2θ) of powder X-ray diffraction using a Cu-Kα ray:
(Crystal A):
7.96±0.40, 8.94±0.45, 9.50±0.48, 10.49±0.52, 11.00±0.55, 11.12±0.56, 13.45±0.67, 13.82±0.69, 16.79±0.84, 17.76±0.89, 18.22±0.91, 19.14±0.96, 19.27±0.96, 19.84±0.99, 20.31±1.02, 20.60±1.03, 21.38±1.07, 22.65±1.13, 24.99±1.25, 25.33±1.27, 26.42±1.32 (°);
(Crystal B):
8.09±0.41, 10.28±0.51, 10.59±0.53, 11.07±0.55, 11.38±0.57, 12.93±0.65, 13.50±0.68, 15.01±0.75, 16.73±0.84, 16.92±0.85, 17.43±0.87, 17.74±0.89, 18.77±0.94, 19.71±0.99, 20.51±1.03, 21.50±1.08, 21.74±1.09, 22.00±1.10, 22.22±1.11, 22.72±1.14, 23.43±1.17, 23.80±1.19, 24.13±1.21, 24.78±1.24, 28.10±1.41 (°); and
(Crystal C):
8.06±0.40, 10.20±0.51, 10.52±0.53, 11.01±0.55, 11.35±0.57, 11.63±0.58, 12.92±0.65, 13.48±0.67, 14.93±0.75, 15.95±0.80, 16.68±0.83, 16.89±0.85, 17.33±0.87, 17.61±0.88, 18.50±0.93, 18.72±0.94, 19.70±0.99, 19.90±1.00, 20.49±1.02, 21.43±1.07, 21.85±1.09, 22.16±1.11, 22.57±1.13, 23.76±1.19, 27.96±1.40 (°).
2 . A method for producing the cytosine-type bridged nucleoside amidite crystals according to claim 1 , comprising a step of dissolving a cytosine-type bridged nucleoside amidite amorphous in a nitrile solvent to obtain precipitated crystals.
3 . A method for producing the cytosine-type bridged nucleoside amidite crystals according to claim 1 , comprising a step of dissolving a cytosine-type bridged nucleoside amidite amorphous in a readily soluble solvent and then adding an insoluble solvent.
4 . The method for producing the cytosine-type bridged nucleoside amidite crystals according to claim 3 , wherein the readily soluble solvent is one or more solvents selected from alcohol solvents, ketone solvents, halogen solvents, ester solvents, and ether solvents, and the insoluble solvent is a hydrocarbon solvent.