## 1 Introduction  
Agricultural pests are highly prevalent and have the potential to lead to decreases in production of over 30% in severe cases, resulting in annual economic losses of billions of dollars [1, 2]. Various strategies have been employed to prevent, reduce, or manage pests in economically important crops, with pesticide application being the predominant and most pervasive method [1]. The development of resistance in a diverse array of pests has resulted from the frequent and indiscriminate application of chemical insecticides in large quantities and excessive dosages [3]. As public concern regarding environmental ecology, health, and safety has increased, numerous high-risk chemical insecticides have been restricted or banned. The development of low-risk, high-efficiency insecticides derived from natural sources has garnered significant interest and progress in recent years [4, 5]. _Penicillium_ produces a wide variety of secondary metabolites that have been found to exhibit anti-bacterial, anti-cancer, anti-fungal, anti-inflammatory, and anti-insect properties, with possible applications in the control of invertebrate pests important in agriculture, animal and human health, and other fields [5; 6]. Indole alkaloid okaramines were initially discovered and characterized in _Penicillium_ (Okaramines A-G [7; 8; 9; 10] and N-R [11]). The congeners were subsequently isolated and identified in _Aspergillus_ (Okaramines H-I [12] and S-U [13]) and _Chrysosporium_ (Okaramine D, H-K, R and Chrokaramine A-E [14]). Okaramines A-D, G, and Q displayed various levels of insecticidal efficiency, with Okaramine B exhibiting the highest level (approximately 0.2 ug/g LD\({}_{50}\)) [15; 16; 17]. A previous study demonstrated that the insecticidal activity of Okaramine B occurs mainly through its interaction with the L-glutamate-gated chloride channel (GluCl), which is expressed abundantly in the insect central nervous system. Additionally, it has a specific preference for insects over humans on ligand-gated anion channel selectivity, making it serve as the lead for a new generation of compounds for use in crop protection [18; 19]. Moreover, in addition to activity, efficient synthesis plays a crucial role in determining the suitability of a molecule for further insecticide development. The extraction yield of Okaramine B from fermentation is limited to 11.2 mg per kilogram substance [17], whereas Okaramine A yields 15.3 mg [20]. However, the limited production of these compounds poses a challenge for further studies. The core biosynthetic gene cluster (_oka_) responsible for the production of Okaramine B in both _Penicillium_ and _Aspergillus_ species has been reported to be comprised of the non-ribosomal peptide synthetase gene _okaA_, the flush-dependent monooxygenase gene _okaB_, the dimethylallyltransferase gene _okaC_, the P450 monoxygenase gene _okaD_, the \(\alpha\)-ketoglutarate-dependent dioxygenase gene _okaE_. Furthermore, the methyltransferase gene _okaF_ and an additional P450 monoxygenase gene _okaG_ have been detected in _P. Orchroloron_ strain ATCC 90288 (formerly AK-40), which has been re-classified from _P. simplicissimum_ to _P. ochroloron_ ([[https://www.atcc.org/products/90288#product-references](https://www.atcc.org/products/90288#product-references)]([https://www.atcc.org/products/90288#product-references](https://www.atcc.org/products/90288#product-references)), accessed on 2 February 2024) [21; 22]. In contrast to the alternative gene clusters associated with secondary metabolite synthesis, the _oka_ gene cluster did not contain or flank any regulatory or transport-related genes. In addition, the regulatory mechanisms of okaramine biosynthesis remain unknown. Artificial synthesis of okaramines is an alternative and efficient method, and there have been reports of the concise total synthesis of Okaramine C [23], M [24], N [25], J, L, and S-U [26]. However, the synthesis of Okaramine A, B, or its congeners with superior insecticidal properties has not yet been documented.