Publication of the week, number 2, 29 November 2013

The paper that caught my eye this week is the following.

Peniciketals A−C, New Spiroketals from Saline Soil Derived Penicillium raistrichii. By Wei-Zhong Liu, Li-Ying Ma, De-Sheng Liu, Yu-Ling Huang, Chun-Hua Wang,*, Shou-Sen Shi, Xiao-Hong Pan,  Xiao-Dong Song, and Rong-Xiu Zhu*.

Pharmacy of College, Binzhou Medical College, Yantai 264003, People’s Republic of China and the Institute of Theoretical Chemistry, School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, People’s Republic of China.

They describe the isolation and structure determination of a novel series of spiroketals, the peniciketals.

penci

Peniciketal A: n = 1, R = OH; Peniciketal B: n = 1, R = H; Peniciketal C: n = 0, R = OH

They all contain a benzo fused 2,8-dioxabicyclo[ 3.3.1]nonane group and an aldehyde. and were isolated from Penicillium raistrichii found in a fungus in saline soil in  China. They are cytotoxic metabolites active against A549, HL.60 and K562 cancer cell lines and are all selective for HL-60 cells having IC50 values of 3.2, 6.7 and 4.5 μM respectively (doxorubicin as positive control).

The amounts of these novel compounds extracted from the fungus is on the low side. From 42g of an ethyl acetate extract 65 mg of peniciketal A, 1.5 mg of B and 2.8 mg of C were isolated. Structure was determined by the usual techniques, NMR in particular NOESY and x-ray. A biosynthetic pathway from the acetyl-malonly pathway was also suggested.

These compounds would make an attractive target for total synthesis. SAR studies to improve the activity could utilise the aldehyde moiety present in all three compounds. However any total synthesis would be expected to be challenging and simpler analogues may well have similar of better biological activity. Which would be the better place to begin the search for more potent compounds. So you synthetic chemists out there here is a nice series to propose for a grant application.

 

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Prof. dangerdackel (199 Posts)


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