The global incidence of end-stage heart failure (HF) is increasing, and a prominent challenge facing heart transplantation as the preferred treatment for patients with end-stage HF is graft myocardial ischemia–reperfusion injury (IRI) [1], [2]. IRI causes the microvascular dysfunction, activation of pro-inflammatory, and pro-fibrotic processes, leading to myocardial damage, which is characterized by primary graft dysfunction at an early stage and progression to cardiac fibrosis and allograft vascular disease at a later stage [3]. Currently, there is no useful surgical method to avoid IRI during organ transplantation, and static cold storage (SCS) is the current standard method to reduce IRI during donor heart preservation, but its protection against IRI is limited [4]. Hypothermia has beneficial effects by delaying hypoxia-induced ATP decline and slowing subsequent organ damage. However, it also induce cell damage in a variety of cell types [5]. At present, the admitted safe preservation time of the currently available preservation solutions is 4∼6 h [6], and prolonged cold ischemia time can significantly reduce the success rate of transplantation [5]. Therefore, the discovery of new cardiomyocyte protective agents against cold ischemic injury is of great significance to prolong the preservation time of donor heart and improve the five-year survival rate of heart transplantation.

The Stachybotrys species are widely distributed in soil and various decaying plant substrates and well-known for the production of notorious toxins which caused numerous cases of livestock and human toxicoses [7]. Over the past few decades, a variety of bioactive and novel scondary metabolites, including trichothecene mycotoxins, isochromans, cochlioquinones, and the prenylated phenol derivatives, were discovered from fungi of this species [7], [8], [9], [10], [11]. These scondary metabolites exhibited a wide range of bioactivities including the inhibition of pancreatic cholesterol esterase, anti-complement and anti-viral activities, enhancers of fibrinolytic plasminogen, and control of Sclerotinia sclerotiorum [6], [7], [8], [9], [10]. The chemically novel and bioactive secondary metabolites of Stachybotry species have made them a research hotspot in the natural product chemistry-related fields.

Natural products have been and continue to be a huge reservoir for successful molecular exploration programs related to drug discovery [12]. Atranones represent an uncommon type of C-alkylated dolabellane diterpenoid derivatives that are defined by a typical 5-11-fused bicyclic carbon skeleton, and they comprise three types: C22, C23, and C24. Since the atranones were first isolated from S. chartarum in 1999 [13], hitherto only 30 atranones have been reported [13], [14], [15], [16], [17], [18], some of which showed antimicrobial activity, cytotoxicity, and enhancement neurite outgrowth capacities. In the course of our ongoing study to explore structurally related compounds, a series of C24 atranones possessing a unique hemiketal ring and a γ-butyrolactone moiety fused to both an 11-membered ring and a conjugated δ-valerolactone moiety were obtained. Herewith, we described the isolation, structural elucidation, and bioactivity evaluation of these compounds (Fig. 1).