Fig. 2: Synthesis of para-aminobenzyl phenanthrene-ketol and its elimination characteristics and protection of medicinally relevant ortho-quinones as para-aminobenzyl ketols. | Nature Chemistry

Fig. 2: Synthesis of para-aminobenzyl phenanthrene-ketol and its elimination characteristics and protection of medicinally relevant ortho-quinones as para-aminobenzyl ketols.

From: Controlled masking and targeted release of redox-cycling ortho-quinones via a C–C bond-cleaving 1,6-elimination

Fig. 2

a, Sodium-dithionite-mediated reductive alkylation of PhQ, 4, with Boc-para-aminobenzyl bromide 5 in a two-phase water/THF system generates benzyl ketol product 6 in 60–70% yield. Upon deprotection of N-Boc, compound 7 is unstable and eliminates to release quinone 4 and a linker by-product via the hydroquinone intermediate 8. TBAB, tetrabutylammonium bromide. b, Kinetics of consumption of 7 and formation of 4 were measured by 1H NMR spectroscopy in moderately acidic solution (pH ≈ 6). Example 1H NMR aromatic region of 7 following 12 h at rt is shown, compared to freshly formed 7 and to 4. c, Elimination reaction followed by relative area of 1H NMR peaks over 30 h at rt. d, Structures of β-lapachone (BL) 1, 3-hydroxy-β-lapachone (HBL) 11, dunnione (DN) 12 and cryptotanshinone (CTN) 13. e, Protection of ortho-quinones 1, 11, 12 and 13 as benzyl ketol derivatives. Upon deprotection the derivatives eliminate to reform the quinones.

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