Due to rarity of the raw materials and low yield of the active ingredient, total synthesis of the compound was devised in 1996.

As a result of the discovery of Calanolide A, Sarawak Medichem pharmaceuticals company was established as a joint venture between US-based MediChem Research Inc and Craun Research Sdn Bhd, a company owned by the Sarawak state government.

In September 1987, a botanist named John Burley went on a mission to collect plant samples from a swamp forest at Lundu, Sarawak, Malaysia.

He and his team routinely collected a kilogram of fruits, leaves, and twigs from each type of plant they encountered.

[1] On return trip to Sarawak in March 1992,[1] it was found that the tree had been cut down by local people most likely for fuel and building material.

The collectors then returned home with samples from other varieties of the Calophyllum lanigerum species, most of which failed to show any anti-HIV properties.

[2] Since the plant source is relatively rare, a method of total synthesis was developed in 1996 which showed same effectiveness against HIV virus when compared to the original compound.

Sarawak Forestry Department was in collaboration with University of Illinois at Chicago (UIC) for sustainable harvest of (-)-Calanolide B.

[1] In June 1993, The Calophyllum Species (Prohibition of Felling and Restriction of Export) Order was issued by the Sarawak state government to ensure adequate supply of the trees for medicinal purposes.

[1][6] In the same year, International Convention on Biological Diversity (CBD) treaty came into effect with 179 countries as its signatories.

[4] NCI also partnered with a small American pharmaceutical company named MediChem Research Inc[9] based in Lemont, Illinois to develop the Calanolide compound.

[4] The Sarawak government entered the joint venture through its wholly owned company named Craun Research Sdn Bhd.

[15] In 2019, Dr Annuar Rapaee, Sarawak Assistant Minister for Education, Science and Technological Research admitted the slow progress in developing and commercialising the drug.

[20] Besides, Calanolide A is also a partially competitive inhibitor of dNTP (deoxyribonucleotide triphosphate) binding site of the enzyme.

Calanolide A, Costatolide, and dihydrocostatolide can be used together with azidothymidine (AZT), indinavir, nelfinavir, and saquinavir for enhanced activity against the HIV-1 virus.

A Phase I clinical trial done in 2001 on 47 healthy subjects showed that the side effects were taste alteration, headache, belching, and nausea.