The limited effects of current treatments of primary myelofibrosis (PM) led us to prospectively evaluate recombinant interferon-␣ (rIFN␣) in "early" PM patients with residual hematopoiesis and only grade 1 or 2 myelofibrosis. Seventeen patients meeting World Health Organization PM diagnostic criteria received either rIFN␣-2b 500 000 to 3 million units 3 times weekly, or pegylated rIFN␣-2a

NK cells have potential therapeutic impact in suppressing graft-versus-host disease (GVHD) and enhancing antitumor effects as a cellular therapy for hematologic malignancies. However, few studies have addressed the trafficking and in vivo behavior of NK cells in murine models of bone marrow transplantation (BMT). We investigated NK cell trafficking and survival following allogeneic and syngeneic BMT using a novel bioluminescence-based imaging strategy. Transplantation of luciferase-expressing NK cells revealed CD62L-mediated trafficking to lymphoid organs and trafficking to GVHD target tissues, as evidenced by in vivo and ex vivo bioluminescence imaging. The NK cells persisted for ∼4 wk after transplantation in allogeneic recipients, but were not detectable in syngeneic recipients. CFSE-labeling studies showed extensive NK cell proliferation in vivo. Transplanted NK cells up-regulated molecules necessary for homing to the lymph nodes, gastrointestinal tract, and skin, yet did not cause clinical GVHD. This expansion and tissue-specific homing was not solely due to the conditioning regimen, as NK cells proliferated and reached lymphoid and GVHD target tissue in unconditioned allogeneic RAG2−/− γ-chain−/− recipients. IL-2 enhanced expansion and antitumor activity of NK cells. These results provide significant insight into the behavior and potential therapeutic impact of NK cells in BMT.

Enantioenriched 2,3,4-trisubstituted thiochromanes have been synthesized by using a cupreinecatalyzed tandem Michael addition-Henry reaction between 2-mercaptobenzaldehydes and β-nitrostyrenes. Good diastereoselectivities and enantioselectivities were obtained for the title compounds, which may be further improved through a single recrystallization (up to 98% de and> 99% ee). KeywordsHenry reaction; 2-mercaptobenzaldehyde; Michael addition; β-nitrostyrene; organocatalysis; tandem reaction Chromanes are an important class of compounds that are found in many biologically active natural products.[1] Thiochromanes, the sulfur analogues of chromanes, have also been reported to possess important biological activities. [2] There are also reports that the replacement of the oxygen atom in chromanes with a sulfur atom results in enhanced bioactivities.[2d,f] Some representative examples are collected in Figure 1. Tertatolol (1) has been shown to have affinity to 5HT A1 receptors in human and rat brains. [2a,b] Thiochromane derivative 2 also displays a mixed binding affinity to dopamine D 2 , D 3 and 5HT A1 receptors, [2d] whereas thiochromane derivative 3 shows potent anti-HIV activity. [2e] Owing to their biological activities, several asymmetric methods have been developed for the synthesis of these compounds, which include asymmetric reduction of thiochroman-4-ones, [3] enzymatic resolution of racemic 4-hydroxythiochromanes or 4-acyloxythiochromanes, [4] and enantioselective alkylation of thiochromanes via conjugate addition.[5] Last year Wang and co-workers reported an enantioselective tandem Michael-aldol reaction for the synthesis of thiochromenes catalyzed by a proline derivative.[6] Most recently, the same group also reported a quinine thiourea-catalyzed tandem Michael-aldol reaction for synthesis of [13] Moreover, the synthesis of thiochromanes by using this tandem reaction has never been studied.[14] Herein, we report an organocatalytic, enantioselective tandem Michael-Henry reaction for the direct synthesis of 2-aryl-3-nitro-4-hydroxythiochromanes.By using 2-mercaptobenzaldehyde (8) and β-nitrostyrene (9) as the model compounds, we initially studied the tandem Michael-Henry reaction using 5 mol% of DABCO as the catalyst at room temperature (entry 1, Table 1). We were pleased to find that the reaction was completed in just 5 min and only two diastereomers of the expected 2-phenyl-3-nitro-4-hydroxythiochromane (10a) were obtained in a ratio of 70:30, according to the 1 H NMR analysis of the crude product. Encouraged by this result, we further screened some readily available alkaloid catalysts 4-7 (Figure 2) in an effort to develop an enantioselective reaction, and the results are summarized in Table 1.As shown in Table 1, with 5 mol% loading of quinine (4) in diethyl ether, the reaction of 8 and 9 proceeds smoothly, and complete conversion was achieved in just 5 min (entry 2). The same two diastereomers were formed in a ratio of 75:25. However, the ee value of the major diastereomer was only 8% fo...

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