Silyl-Group Boosted Internal Redox Reaction: Hydride Shift from an Aliphatic Secondary Position for the Formation of Six- and Seven-Membered Carbocycles.

We report a hydride shift/cyclization reaction at the aliphatic secondary position (methylene group). The key to accomplishing this reaction was the employment of benzylidene malonate having a silyl group ß to the hydride donor carbon. When the corresponding malonates were treated with a catalytic amount of Al(OTf)3, the [1,5]-hydride shift from the simple aliphatic secondary position proceeded smoothly to afford silyl-group substituted tetralin derivatives in excellent chemical yields (up to 98%). This reaction system was applied to the formation of seven-membered carbocycles via the [1,6]-hydride shift mediated process.

Characterization of two cytochrome P450 monooxygenase genes of the pyripyropene biosynthetic gene cluster from Penicillium coprobium.

Pyripyropenes are potent inhibitors of acyl-CoA:cholesterol acyltransferase, which were initially discovered to be produced by Aspergillus fumigatus. Recently, Penicillium coprobium PF1169 has also found to produce pyripyropene A (PyA), which exhibits insecticidal properties. Pyripyropenes are natural hybrid products of both terpenoid and polyketide origin. In our research, based on data generated using the Genome Sequencer FLX for P. coprobium PF1169, we predicted the biosynthetic gene cluster of PyA by blast analysis comparing with polyketide synthase and prenyltransferase of other species. By screening the genomic fosmid library, nine open reading frames (ppb1 to ppb9) related to the biosynthesis of PyA were deduced. Among them, two cytochrome P450 monooxygenase genes (ppb3 and ppb4) were separately introduced into the model fungus A. oryzae. Bioconversion of certain predicted intermediates in the transformants has elucidated the manner of hydroxylation in the biosynthetic pathway by the expressed products of these two genes (P450-1 and P450-2). That is, P450-1 exhibits monooxygenase activity and plays the hydroxylation role at C-11 of pyripyropene E. While P450-2 plays an active role in the hydroxylation of C-7 and C-13 of pyripyropene O.

Perfusion weighted magnetic resonance imaging to distinguish the recurrence of metastatic brain tumors from radiation necrosis after stereotactic radiosurgery.

After stereotactic radiosurgery (SRS) for brain metastases, delayed radiation effects with mass effect may occur from several months to years later, when tumors may also recur. Aggressive salvage treatment would be beneficial for patients with recurrence, but may be contraindicated for those with dominant radiation effect. Conventional magnetic resonance (MR) imaging does not provide sufficient information to differentiate delayed radiation effects from tumor recurrence. Positron emission tomography, MR spectroscopy, and other modalities sometimes may lead to false findings of tumor recurrence. We prospectively applied perfusion MR imaging for the management strategy after SRS because it gives microvascular information about the lesions. Twenty-eight lesions were enlarged on serial MR images in 27 patients 2-35 months (median: 11.8 months) after SRS for metastatic brain tumors. Each patient underwent MR perfusion imaging within a month after appearance of the growing enhanced lesion. To calculate the relative cerebral blood volume ratio (rCBV ratio), the regions of interest were located in the enhanced areas on the contrast-enhanced T1-weighted images and compared with the corresponding contralateral normal brain tissue. They were then followed-up with scheduled MR images with gadolinium enhancement at 1 to 2-month intervals afterward. Lesions which progressively increased in size on MR images were diagnosed as recurrences; lesions which disappeared or decreased in size were diagnosed as radiation necrosis. In addition, two lesions surgically removed were diagnosed by pathological examination. Follow-up MR images revealed that 21 of 28 lesions were radiation necrosis. Five lesions were diagnosed as recurrence on MR images, and the other two lesions were revealed as recurrence by pathological examination. An rCBV ratio of greater than 2.1 provided the best sensitivity and specificity for identifying recurrent metastatic tumors, at 100 and 95.2%, respectively. Perfusion MR imaging provides useful, less invasive and in-vivo information for management of growing lesions after SRS, and rCBV may be a valuable index for this diagnostic purpose.