As a novel and highly potent long-acting HIV capsid protein inhibitor, 1 lenacapavir (1, GS-6207, brand name: Sunlenca, Figure ) is able to reduce HIV infection by 96% and was very recently approved by the US Food and Drug Administration (FDA) as an antiretroviral drug for HIV treatment. 2 Due to its outstanding potency, low in vivo systemic clearance, slow release kinetics, and minimal cross-resistance with previously approved antiretroviral drugs, lenacapavir presents an excellent opportunity for the treatment of multi-drug resistant HIV. In light of the excellent efficacy, an efficient, sustainable, and selective synthesis of lenacapavir represents an essential goal for the advancement of global health, particularly in developing countries, and has thus captured the attention of philanthropic foundations in the public health domain. As a structurally complex small-molecule drug, lenacapavir features an unusual chiral 5/5/3 fused tricyclic fragment ((3bS,4aR)-2) possessing a cis-cyclopropane moiety. Gilead Biosciences' disclosed synthetic route towards this 5/5/3 fused tricyclic compound hinges on the use of chiral separation by preparative supercritical fluid chromatography (SFC) or employing chiral starting materials with somewhat reduced synthetic efficiency (Figure ). Therefore, alternative efficient and stereoselective routes based on catalytic asymmetric (bio)transformations could potentially streamline the production of this clinically significant drug.