The invention discloses a preparation method of an antimicrobial compound Myrtucommulone J, an anticancer compound Myrtucommuacetalone and analogues of Myrtucommulone J and Myrtucommuacetalone. The method comprises the following steps: target products are prepared from unsaturated ketone compounds and monoacyl phloroglucinol compounds in a nonpolar solvent under the action of a trifluoroacetic acid, acetic acid or p-toluenesulfonic acid catalyst through a reaction. Biomimetic total synthesis is realized for the first time, the structure of Myrtucommulone J is further confirmed, and one efficient, reliable and economical preparation method is provided for abundant obtaining of Myrtucommulone J, Myrtucommuacetalone and the analogues of Myrtucommulone J and Myrtucommuacetalone as well as subsequent structure-function relationship and druggability based development and production.