Polysialic acids (PSAs) are polymers of N-acetylneuraminic acid. Depending on their glycosidic linkages, these sugar polymers exist in nature as a-2,8-, a-2,9-, and a-2,8/2,9-linked polysaccharides. [1] PSAs have been reported to demonstrate many important biological functions. [2] For example, a-2,8-PSA is mainly linked to the neural cell adhesion molecule (N-CAM). This homopolymer of sialic acid has been implicated in reducing N-CAM adhesion; removal of the PSA increases the adhesive capability of N-CAM. In addition, a-2,8-and a-2,9-PSAs are the capsular polysaccharides of, respectively, serogroups B and C of Neisseria meningitidis, a leading worldwide cause of meningitis and rapidly fatal sepsis in otherwise healthy individuals. Structural diversities of PSAs are even more complicated with the possibility of PSA lactonizations. For a-2,8-PSA, the C-2 carboxylic acid of one residue can condense with the C-9 hydroxyl group of an adjacent residue to generate a d-lactone under acidic conditions. Such d-lactonizations have also been complex 5 was also prepared using a one-pot procedure starting with tetrabutylammonium perrhenate and triphenylphosphane hydrochloride in dichloromethane (entry 4, Table ).
These examples illustrate a new strategy for labeling estradiol ligands with rhenium using a solid-supported hydrazine substrate, and this chemistry should also be successful for preparing technetium analogs. [12] The ability to use perrhenate and pertechnetate salts for labeling is particularly advantageous, since these species are obtained directly from the radionuclide generators. The efficiency and convenience of this approach can be extrapolated to a new generation of rhenium and technetium complexes for diagnostic and therapeutic applications in nuclear medicine. Further studies that are currently in progress involve evaluation of the receptor binding affinity and in vivo stability of these estradiol derivatives, and the extension of this technology to other low-capacity receptor systems.
Experimental Section
4: To a suspension of Tentagel Carboxy resin (1.0 g, 0.26 mmol) in dichloromethane (50 mL) was added PyBOP (405 mg, 0.78 mmol) followed by hydrazine 3 and diisopropylethylamine (0.3 mL). The resulting suspension was stirred at 25 8C for 20 h. The reaction product was filtered to give the yellow polymer support 4. FT-IR (KBr): n ร 3443, 2869, 1652, 1611, 1104 cm ร1 . 5: A suspension of 4 (110 mg, 0.0286 mmol), triphenylphosphane (7.5 mg, 0.0286 mmol), and [ReOCl 3 (PPh 3 ) 2 ] (23.8 mg, 0.0286 mmol) in dichloromethane (10 mL) was heated at 40 8C for 3 h. The reaction mixture was filtered, and washed thoroughly with dichloromethane. The combined organic layers were concentrated, and the product was precipitated from dichloromethane/hexanes and recrystallized to provide the complex 5 (28 mg, 82 %) as olive-green crystals containing CH 2 Cl 2 . Elemental analysis for C 62 H 57 Cl 3 NO 2 P 2 Re ยด0.5 CH 2 Cl 2 : calcd: C 60.23, H 4.61, N 1.12; found: C 60.29, H 4.66, N 1.50. Spectral data is provided in the Supporting Information.