Diterpenoid pyrones

Coupling of CM and intramolecular substitution to domino processes leading to tetrahydrofurans is feasible as well [38]. However, a corresponding combination to give tetrahydropyrans is better carried out as a sequential process [38d]. Reaction of the terminal olefin 184 with allyl chloride catalyzed by ruthenium complex 2 led to tetrahydrofuran 185 by a completely diastereoseleclive cyclization of the intermediate CM product (Scieme 2.65) [38a,b]. Compound 185 was then successfully advanced to the immunosuppressive diterpenoid pyrone subglutinol B. 

Goetz, M. A., Zink, D. L., et al. (2001) Diterpenoid pyrones, novel blockers of the voltage-gated potassium chaimel Kvl.3 from fungal fermentations. Tetrahedron Lett. 42(7), 1255-1257. 

Total Synthesis of Diterpenoid Pyrones, Nalanthalide, Sesquicillin, Candelalides A-C, and Subglutinols A, B... 

In recent years, a number of diterpenoid pyrones and related compounds have been isolated from microorganisms, particularly from fungal strains [1-6]. Several of these natural products have been reported to exhibit a wide variety of biological properties such as insecticidal [1,3c], antihypertensive [3d], bronchospasmolytic [3d], anti-inflammatory [3d], laxative [3d], anticancer [3e], and immunosuppressive activities [3-6]. In most cases, however, further biological studies including structure-activity relationships (SARs) are severely restricted probably because of the limited structural diversity of microorganisms. Consequently, the development of efficient and flexible synthetic methods for this class of natural products and related compotmds is quite desirable and worthwhile from the viewpoint of medicinal chemistry and pharmaceuticals. 

In this chapter, the total synthesis of biologically attractive diterpenoid pyrones— nalanthalide (1), sesquicillin (2), candelalides A-C (3-5), and sub-glutinols A (6), B (7)—has been summarized with particular focus on then-synthetic strategies. It is of interest to look at each respective method for approaching the target molecules. 

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