Abstract: An improved and practical synthesis of racemic 11-demethylcalanolide A ［(±)-1］ was developed. This improved process involved Pechmann reaction on phloroglucinol with ethyl butyrylacetate to give 5,7,-dihydroxy-4-n-propylcoumarin (3). Poly phosphoric acid (PPA) catalyzed acylation of compound (3) with crotonic acid, then intramolecular cyclization was achieved simultaneously in one step to afford the key intermediate chromanone (4). A microwave assisted synthetic method preparing chromene (6) using chromenynation of chromanone (4) with 1,1-diethoxy-methyl-2-butene was conducted. Luche reduction of chromene (6) using NaBH₄ with CeCl₃·7H₂O preferably gave (±)-1. The overall yield of this four step synthesis of (±)-1 was around 32% increasing one fold more than that of the previous method. An in vitro investigation showed that (±)-1 exhibited inhibitory activities against both wild-type and drug-resistant HIV-1 in HIV-1 RT and cell culture assay, and significant synergistic effects in combination with AZT, T-20, and indinavir. Its LD₅₀ of acute toxicity in mice by intragastric administration and by intraperitoneal injection were 735.65 mg·kg^-1 and 525.10 mg·kg^-1, respectively. The C_max and AUC_0-∞ were 0.54 μg·mL^-1 and 1.08 (μg·mL^-1)·h, respectively. The dynamics study of the inhibition of mice sera on HIV-1 RT showed that mice treated with 100 mg·kg^-1 (±)-1 once intraperitoneally were similar to that of 5 mg·kg^-1 of known clinical effective anti-HIV-1 drug neverapine. The results suggested that further investigation of the anti-HIV candidate (±)-1 was warranted.