First synthesis of 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol from 1‐ and 2‐naphthol derivatives

Abstract

Two new structurally isomeric, 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[h]chromen‐2‐yl)‐1‐naphthol (1) and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2H‐benzo[g]chromen‐2‐yl)‐2‐naphthol (3) have been synthesized from 2‐acetyl‐1‐naphthol and ethyl‐3‐hydroxy‐2‐naphthoate, respectively, involving Grignard reaction, dehydration of the corresponding tertiary alcohols, and hetero Diels–Alder dimerization. The two benzochromenes (1 and 3) have been fully characterized by IR, NMR, and HRESIMS data. Their structures are further supported by crystallography of their corresponding acetates (2 and 4). J. Heterocyclic Chem., (2011).

Inulavosin and its benzo‐derivatives, melanogenesis inhibitors, target the copper loading mechanism to the active site of tyrosinase

“…We applied them to the culture medium and observed their effects on cell pigmentation using B16 melanoma cells, as described previously (Fujita et al., ). The two structurally isomeric compounds, 2‐(2,4,4‐trimethyl‐3,4‐dihydro‐2 H ‐benzo[ h ]chromen‐2‐yl)‐1‐naphthol 2 and 3‐(2,4,4‐trimethyl‐3,4‐dihydro‐2 H ‐benzo[ g ]chromen‐2‐yl)‐2‐naphthol 4, and their corresponding acetates ( 3 and 5, respectively), (Menezes et al., ) effectively inhibited hyperpigmentation of the cells to the same extent as 1 (Figure B). However, the 2‐phenyl chroman 6 showed no inhibitory effects.…”

“…Inulavosin 1 (as racemic mixture) was synthesized by POLA Chemical Industries, Inc., Yokohama, Japan. Racemic compounds 2 – 5 were synthesized and characterized by procedures reported earlier (Menezes et al., ; Srinivasan et al., ). Compound 6 was synthesized by hetero‐Diels Alder reaction of 2‐hydroxybenzyl alcohol with styrene and characterized by NMR.…”

“…Here, to understand the structure–activity relationship in the inhibitory effect of 1 , we tested several racemic benzo‐derivatives ( 2 – 5 ; see Figure A) (Menezes et al., ) which share the 2‐phenyl chroman 6 structure with 1 . Based on the results obtained through biochemical experiments on compounds 2 – 5 and representative molecular docking simulations of 1 , 2, and 4 to tyrosinase, we propose a novel mechanism underlying the 1 and its derivatives‐induced lysosomal degradation of tyrosinase in melanocyte.…”

Nucleophilic Addition Reaction with Dearomatization of Naphthalene Ring

“…The selectivity for 1,2-and 1,4-additions changed depending on the type of organolithium species used (entries 8-10). Only 1,2-adducts were obtained in high yields when using MeLi and PhLi (entries 8 and 9), with combined yields of the corresponding ketones (9b 23) and 9c 24) ) and alcohols (10b 25) and 10c 26) ) of 94 and 86%, respectively. Meanwhile, the ratio of 1,2-and 1,4-additions using n-BuLi was about 1 : 1 (entry 1).…”