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Current treatment for leukemia largely depends on chemotherapy. Despite the progress in treatment efficacy of chemotherapy, a poor outcome consequent upon chemoresistance against conventional anti-cancer drugs still remains to be solved. In this study, we report 5-diphenylacetamido-indirubin-3′-oxime (LDD398) as a novel mitochondria-targeting anti-leukemic agent, which is a derivative of indirubin used in traditional medicine. Treatment with LDD398 resulted in caspase activation, cell death, and growth arrest at G2/M phases in leukemia cells. Interestingly, LDD398 quickly collapsed mitochondrial membrane potential (MMP) within 1 h, accompanied by cytochrome c release into cytosol and severe depletion of cellular ATP. However, the LDD398-induced cellular events was significantly mitigated by blockage of mitochondrial permeability transition pore (MPTP) opening with chemical and genetic modifications, strongly supporting that LDD398 executes its anti-leukemic activity via an inappropriate opening of MPTP and a consequent depletion of ATP. The most meaningful finding was the prominent effectiveness of LDD398 on primary leukemia cells and also on malignant leukemia cells resistant to anticancer drugs. Our results demonstrate that, among a series of indirubin derivatives, LDD398 induces leukemia cell death via a different mode from indirubin or conventional chemotherapeutics, and can be employed as a potent anti-cancer agent in the treatment for newly diagnosed and relapsed leukemia. © 2015 Wiley Periodicals, Inc.

Objective: This study was conducted to explore the possible influence of risk notification regarding breast cancer on the intention of women to undergo mammography. Methods: This study employed an uncontrolled before–after design. A baseline survey was conducted in a random sample of 1000 women to examine the sociodemographic variables, breast cancer risk factors, and screening-related variables. All subjects received the findings of a personalized health-risk appraisal (HRA) following the baseline interview. After 2 months of the baseline survey, a survey was conducted in 855 women to assess whether the intention of undergoing mammography had changed. Thus, the modification in the intention by communicating the individual risk status was assessed. Results: There was an overall increase from baseline to post-intervention in the number of subjects with the intention of undergoing mammography. Women in the contemplation and action stages who had intention toward mammography utilization at baseline showed decreased intention regarding mammography. After intervention in the form of HRA to promote mammography utilization, it was determined that young age, being married, being in neither the precontemplation nor the relapse stage, and having one or more risk factors of breast cancer were the predictors of intention to undergo mammography. Conclusions: Our findings indicate that communicating the risk status by HRA service can have a negative effect in the promotion of health-conscious behavior. The selection of the appropriate type of intervention using HRA to promote mammography utilization in the target group will be enhanced by taking into account the risk status of each client. Copyright © 2009 John Wiley & Sons, Ltd.

Tedanolide (1), an 18-membered macrolide, was isolated by Schmitz et al. in 1984 from the Caribbean sponge Tedania ignis and structurally related 13-deoxytedanolide (2) was isolated from a Japanese sea sponge, Mycale adhaerens, by Fusetani et al. in 1991. Both tedanolide (1) and 13-deoxytedanolide (2) exhibit very potent biological activities against certain tumor cell lines. Their complex structures and distinctive biological properties make them extremely attractive targets for synthetic chemists. Recently Kalesse and Smith have reported successful total syntheses of tedanolide (1). As shown in Scheme 1, our retrosynthetic strategy for tedanolide (1) was the disconnection to two subunits 4 and 5 via cleavage at ester C-O bond and the aldol condensation transformation. The subunit 5 was envisioned to be obtained from the coupling between precursors 6 and 7. Herein we disclose our efforts in the construction of the C1-C7 fragment 6 of tedanolide (1). At first stage, we have utilized the Roush protocol as a key methodology toward fragment 6. The synthesis began with the known aldehyde 9. The Roush asymmetric crotylation upon 9 with 10 gave the desired product in 80% yield as a 92:8 mixture of two diastereomers, which was methylated to the methyl ether 11 in good yield. Ozonolysis of 11 furnished aldehyde 12. The second Roush crotylation on 12 did not yield the desired product. Instead we obtained a mixture of diastereomers (Scheme 2). Because of the observed lability of aldehyde 12 during the second crotylation, we considered the modification of the synthetic pathway. As a replacing measurement for the second Roush crotylation, we devised the combined application of Sharpless asymmetric epoxidation and Gilman cuprate reaction. As shown in Scheme 3, we established a highly stereoselective synthesis of precursor 6 via epoxide ring-opening and Mitsunobu reaction. The oxidative cleavage of the terminal vinyl group of 11 followed by immediate HornerWadsworth-Emmons reaction provided α,β-unsaturated ester 15 in 75% yield over two steps (trans:cis = 96:4). Subsequent reduction of ester 15 using DIBAL-H gave the intermediate allylic alcohol and Sharpless epoxidation upon this alcohol with Ti(OPr)4, L-DET and TBHP afforded stereoselectively epoxide 8 in nearly quantitative yield (β/α ≥ 30). Epoxide ring opening of 8 by the treatment with MeLi and CuI furnished the intermediate 1,3-diol (1,3-diol:1,2diol = 88:12) and the exposure of the resulting 1,3-diol to 16 with PPTS yielded p-methoxyphenyl acetal 17 in 70% yield. To introduce the requisite stereochemistry at C2, the

The macrolide (+)-sorangicin A (1), isolated by Hofle and co-workers from the gliding myxobacterium Sorangium cellulosum, has highly effective biological activity against a broad panel of both Gram-positive and Gram-negative bacteria, displaying average MIC values of 10 ng/mL and 10 μg/mL, respectively. The mechanism of action has been shown to be the inhibition of RNA polymerase in both Escherichia coli and Staphylococcus aureus. In addition, sorangicin A is active in vitro against several cancer cell lines. This fact motivated us to be interested in the synthesis toward sorangicin A. One of key steps in our synthetic plan is the successful preparation of dihydropyran. There have been numerous synthetic efforts reported in the literature. In general, dihydropyran units has been elegantly constructed by reactions such as Claisen rearrangement, Ferriertype reaction, radical, hetero Diels-Alder cyclizations and a few other reactions. We sought new and concise synthetic methods for this ring. Herein, we describe two new and simple preparations of the dihydropyran moiety based on olefinic ring-closing metathesis (RCM) reaction employing Grubbs catalyst. We planned two pathways according to retrosynthetic concept included formation of the C11-C12 double bond by RCM reaction (Scheme 1). First route A is employing oxazolidinone to yield the syn-aldol product. This methodology was implemented by Crimmins and She. The second route B is utilizing enantiospecific rhodium-catalyzed allylic etherification with the copper(I) alkoxide as a nucleophile. In the first reaction pathway A according to our synthetic plan (Scheme 2), the alcohol 5 was reacted with sodium salt of bromoacetic acid in refluxing THF to give glycolic acid, which was converted to its mixed pivalic anhydride and treated with (R)-3-lithio-4-benzyl-2-oxazolidinone to generate the N-glycolyloxazolidinone 7 in 81% yield over two steps. The addition reaction of 7 with acrolein furnished hydroxy compound 8 in good yield and high diastereoselectivity (73%, 93:7 dr by H NMR analysis). Protection of the resulting alcohol 8 as its TBS ether 3 and reductive removal of the chiral auxiliary group afforded primary alcohol 9 in 83% yield. The olefinic RCM reaction in the presence of Grubbs’ catalyst in CH2Cl2 transformed 9 to the desired dihydropyran compound 2. In the more convenient second synthetic approach B to dihydropyran 2 (Scheme 3), the stereospecificity in the reaction of rhodium-catalyzed allylic etherification could be maintained by suppressing the rate of isomerization. The copper(I) alkoxide as a nucleophile served to promote the etherification. Thus, this reaction allows for net retention of the absolute configuration through the alkylation of a rhodium-enyl complex. We began the second pathway with an aldol addition of chiral oxazolidinone 10 to acrolein to give syn-aldol adduct (84%, 92:8 dr by H NMR analysis). Protection of the resulting secondary hydroxy group as its TBS ether 11 and reductive removal of the chiral auxiliary group afforded an intermediate primary alcohol in 92% yield. Then, silylation of the hydroxy group as the TBS ether and removal of the MPM group yielded the alcohol 12 in 93% yield. Treatment of the allylic carbonate 13 with the trimethylphosphitemodified Wilkinson catalyst and the copper(I) alkoxide derived from the alkenyl alcohol 12, afforded the diene 4 in 67% yield with excellent diastereoselectivity (98:2 dr by H NMR analysis). The high selectivity observed can be explained using the reported proposed mechanism. Desilylation of the primary hydroxyl group with CSA gave alcohol 14 in 76% isolated yield. Finally, The RCM reaction was

in order to find the optimum reaction condition for theconstruction of C13-C15 homoallylic alcohol unit oflaulimalide. Also, we examined the stereoselective effects ofindium metal in the presence of Lewis acids and chiralligands on allylation. We successfully demonstrated that theindium-mediated allylation reaction of (2