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AMP-activated protein kinase α1 (AMPK α1) is involved in the tumorigenesis of various cancer types. However, the role of AMPK α1 in non-small cell lung cancer (NSCLC) remains unclear. In the present study, 99 NSCLC tumor tissues and paired normal tissues were obtained. The expression levels of AMPK α1 were significantly upregulated in NSCLC tumor tissues compared with those in adjacent non-tumor lung tissues. The patients were further divided into two groups according to their expression levels of AMPK α1 in tumor tissues. The results outlined that overexpression of AMPK α1 was associated with poor prognosis. In addition, vascular endothelial growth factor (VEGF) expression levels were associated with malignant progression in patients with NSCLC. Patients with NSCLC that overexpressed AMPK α1 and VEGF had the worst outcomes. Moreover, AMPK α1 may positively regulate VEGF expression. These results suggest that AMPK α1 serves a carcinogenic role at least in part through the regulation of VEGF expression, and thus represents a potential treatment target in patients with NSCLC.

Determination of structure of a new peroxidic product 3 obtained from the degradation of arteannuin 1 and lactone configuration of the related compound 4 by means of chemical transformation and X-ray analysis are described.

Arteannuin 1 is a new sesquiterpene lactone containing a peroxide linkage and is an antimalarial principle isolated from Artemisia annua L. . R(+)-Citronellal 5 as a starting material for the total synthesis was converted into 11R(-)-methyl dihydroarteannuinate 12 in 14 steps. The key intermediate 4 was obtained from compound 12 in 5 steps. The introduction of hydroperoxide in 4 by photooxidation followed by acid treatment gave 1 . Hydroxylation of 4 with osmium tetraoxide afforded deoxyarteannuin 2 .

This paper deals with the determination of the A,B ring configuration of artean- nuic acid(1)using circular dichroism(CD).The 5-oxo-compound 7 was prepared from the methyl arteannuinate(4)through epoxidation with m-CPBA followed by treatment with BF_3·Et_2O.Epimerization of 7 with alkali produced its epimer 8.Since 7 exhibited a negative Cotton effect near 294nm,8 exhibited a positive Cotton effect near 292 nm,a cis A,B ring fusion for 7 and a trans A,B ring fusion for 8 might be assigned respectively.The prediction from the octant rule is in consistent with the experimental result. Therefore the cis A,B ring fusion for arteannuic acid was establi- shed.In a similar way,compounds 13a,b and 14 were obtained from methyl dihydroa- rteannuinate 11.Compound 13a,b showed the same sign as that of 7 and compound 14 that of 8.Thus the cis A,B ring configuration of arteannuic acid was confirmed. β-Epoxide 6 or 15 was treated with BF_3.Et_2O to give a mixture of 5-oxo-compound 9 or 16 and an aldehyde 10 or 17,which was difficult to be separated.The formation of 18 or 17 was postulated to be the result of a Wagner-Meerwein type rearrangement. Epimerization of 9 or 16 with alkali produced the trans A,B ring fused isomer 8 or 14. On the basis of benzene induced solvent shift △(CDC1_3-C_6D_6)and reaction mecha- nism,the methyl group at C_4 in compounds 7,8 and 13a,b were assigned as having α- configuration.

Arteannuin E was synthesized from methyl β-epoxy arteannuinate by treatment with formic acid followed by hydrolysis and lactonization. Methyl α-epoxy arteannuinate or methyl α-epoxy dihydroarteannuinate treated with formic acid did not produce the trans-diaxial product. Arteannuin E (1) and arteannuin F (2) exist together with the arteannuin (3) in Artemisia annua L.1 The structures were determined1 and 2 was synthesized.2 The structure difference lies in the different fusion of their lactone rings. In this paper we will report the synthesis of 1 and the epoxy fission reaction of the methyl α-epoxy arteannuinate (4).

This paper reports the total synthesis of 11 R(-)-methyldihydroarteannuate (3) starting from 10 R (+)-citronellal (4). Compound 3 has already been used as starting material for the synthesis of arteannuin (1) through the photooxygenation of the key intermediate compound 2 by us. Thus, the total synthesis of arteannuin from 4 was accomplished. 10R(+)-citronellal (4) was submitted to cyclization and hydroboration to afford dihydroxy compound 5. After selective benzylation of the primary hydroxyl group, oxidation gave the ketone 6. Kinetic deprotonation of 6 and treatment of the resulting enolate with 3-trimethylsilyl-3-buten-2-one provided 1, 5-diketone 7. Cyclization of 7 with Ba(OH)_2·8H_2O and dehydration of the cyclization product with oxalic acid gave α, β-unsaturated ketone 8. 8 was reduced with sodium borohydride, and the reduction product was oxidized to the ketone 9. Both compounds 8 and 9 all showed a positive CE in its CD, therefore the α-orientations of 1-H in 8 and 6-H in 9 could be assigned respectively. When 9 was reacted with methyl Grignard reagent followed by dehydration with p-TsOH, a mixture of 10 and its △~3-isomer was obtained in 1:1 ratio, and pure 10 was isolated from the mixture by flash chromatography. Debenzylation followed by oxidation of the resulting alcohol gave 11. Compound 11 was esterified with CH_2N_2 to give the target compound 3 which is identical in all spectroscopic characteristics with those of 3 obtained from reduction of methyl arteannuate.