51103-58-3

We efficiently synthesized (+)-sesquicillin (a glucocorticoid antagonist) and (-)-nalanthalide (a potassium channel Kv1.3 blocker) in a convergent and unified manner starting from (+)-5-methyl-Wieland-Miescher ketone. The synthesis involved the following key steps: (i) a [2,3]-Wittig rearrangement of a stannylmethyl ether to install the stereogenic center at C9 and the exo-methylene functionality at C8 present in the tran/decalin portion, (ii) a coupling reaction of a trans-decalin portion with a γ-pyrone moiety to assemble the requisite whole carbon framework, and (iii) a conversion of a γ-pyrone moiety to an α-pyrone ring to produce (+)-sesquicillin. The present total synthesis has verified the absolute configuration of these natural products.

To date, entomopathogenic fungi have not been extensively examined by natural product chemists. In this study, we isolated novel pyrone diterpene-type compounds, metarhizins A (1) and B (2), from methanol extracts of entomopathogenic fungus, Metarhizium f

The key step in the total synthesis of sesquicillin (3) is a stereoselective Claisen rearrangement of 1 to afford 2. The synthesis also features an efficient sequence to install an α-pyrone moiety in a hindered environment; TBS = tert-butyldimethylsilyl.