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Both leucovorin and folic acid can be transformed by different enzymes into 5-methyl-tetrahydro-folate, which efficiently crosses the BBB using the folate receptor alpha (FR) transporter, and is thought to be the main active folate in the CNS 99,100

Following the above general procedure F, A and B respectively and starting from the commercially available 4-chloro-3-nitrobenzoic acid (Scheme 4), the crude reaction mixture was purified by column chromatography (dichloromethane:methanol=40:1) to provide the desired tert-butyl 3-amino-4-(2-adamantylamino)-benzoate (SRS16-82, Scheme 4) (700 mg, 2.046 mmol, 88% (3 steps)

The injection sites heal quickly, and any initial tenderness or swelling subsides fast

iScience 14 , 210225 (2019)