Scheme 1

Synthesis of 1’-psoralen-conjugated deoxyribose phosphoramidite (12). Reagents and conditions: (i) trimethylsilyl cyanide (1.5 equiv), BF₃·Et₂O (0.3 equiv), CH₂Cl₂, RT, N₂, 1 d, 58% yield; (ii) 1. 28% NaOMe solution in Methanol (6 equiv), H₂O (3 equiv), Methanol, RT, 4 h; 2. strong acidic cation exchange resin No. 4 (8% cross-linking, 50-100 mesh, H type, 21 g), RT, 1 h, 68% yield; (iii) TBSCl (3 equiv), imidazole (3 equiv), CH₂Cl₂, RT, N₂, overnight, 71% yield; (iv) 1 M NaOH solution (1 equiv), MeOH/THF (1:1), RT, N₂, 0.5 h, 98% yield; (v) 5-aminopentanol (2 equiv), HBTU (2 equiv), triethylamine (4 equiv), CH₂Cl₂, RT, N₂, overnight, 76% yield; (vi) methanesulfonyl chloride (1.2 equiv), pyridine, RT, N₂, 3 h, 87% yield; (vii) 5-hydroxypsoralen (1.2 equiv), potassium carbonate (1.2 equiv), DMF, 60 ˚C, N₂, 3 h, 96% yield; (viii) 1 M solution of tetrabutylammonium fluoride in THF (2.4 equiv), THF, 60 ˚C, N₂, 2 h, 70% yield; (ix) 4, 4ʹ-dimethoxytrityl chloride (1.1 equiv), pyridine, RT, N₂, 1.5 h, 86% yield; (x) 1H-tetrazole (1.2 equiv), 2-cyanoethyl N,N,N’,N’-tetraisopropylphosphordiamidite (1.2 equiv), CH₂Cl₂, RT, N₂, 1.5 h, 87% yield.