The treatment of cancer remains one of the most challenging problems for humanity. Boron neutron capture therapy (BNCT) is a binary approach for cancer treatment that is particularly attractive in treating high-grade gliomas and metastatic brain tumors. Among types of boron-containing molecules used as BNCT agents, boronated amino acids have received significant attention for their preferentially uptake by growing tumor cells. This review emphasizes the synthesis of boronated amino acids.

There is a pressing need for new and more efficient boron delivery agents to tumor cells for use in boron neutron capture therapy (BNCT). A class of boronated unnatural cyclic amino acids has demonstrated a remarkable selectivity toward tumors in animal and cell culture models, far superior to currently used agents in clinical BNCT. One of these amino acids, 1-amino-3-boronocyclopentanecarboxylic acid (ABCPC), has shown a tumor to blood ratio of 8 and a tumor to normal brain ratio of nearly 21 in a melanoma bearing mouse model. This work represents further biological characterization of this compound for tumor targeting in an EMT6 murine mammary carcinoma mouse model and a T98G human glioblastoma cell line. Female BALB/c mice bearing EMT6 tumors were injected with the fructose complex form of racemic mixtures of cis-and trans isomers of ABCPC in identical concentrations. Boron concentrations were measured in the tumor, blood, brain, skin, and liver tissues at 1, 3, and 5 hr post injection. These observations revealed a remarkable difference in racemic mixtures of cis and trans isomers in tumor targeting by boron. This implies that further separation of the L and D forms of this compound may enhance tumor targeting to an even higher degree than that provided by the racemic mixtures. Since the uptake measurements were made in homogenized tumor and normal tissues, little is known about the subcellular location of the boron arising from the various isomeric forms of the amino acid. To study subcellular delivery of boron from ABCPC in T98G human glioblastoma cells, we employed secondary ion mass spectrometry (SIMS) based technique of ion microscopy, which is capable of quantitatively imaging isotopic (elemental) gradients in cells and tissues at 500 nm spatial resolution. The T98G cells were exposed to the nutrient medium containing 100 ppm boron equivalent of a mixture of both L and D isomers of ABCPC in the form of a fructose complex for 1 hr. Following this treatment, the cells were fast frozen, freeze-fractured, and freeze-dried for SIMS analysis. Within an hour of exposure, ABCPC provided partitioning of intracellular to extracellular boron of 3/1. SIMS imaging revealed that boron from ABCPC was distributed throughout the cell, including the nucleus. This level of boron delivery within an hour of exposure is superior to p-boronophenylalanine (BPA) and sodium borocaptate (BSH), which have been previously studied by SIMS in the same cell line. These encouraging observations provide compelling support for further isomeric separations of ABCPC into the D and L forms for enhanced tumor targeting and continued testing of these compounds as new boron carriers in BNCT.

Aims: The aim was to isolate, identify and characterize endophytes from pigeon pea (Cajanus cajan [L.] Millsp.), as novel producer of cajanol and its in vitro cytotoxicity assay. Methods and Results: Isolation, identification and characterization of novel endophytes producing cajanol from the roots of pigeon pea were investigated. The endophytes were identified as Hypocrea lixii by morphological and molecular methods. Cajanol produced by endophytes were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). R-18 produced the highest levels of cajanol (322Á4 AE 10Á6 lg l À1 or 102Á8 AE 6Á9 lg g À1 dry weight of mycelium) after incubation for 7 days. The cytotoxicity towards human lung carcinoma cells (A549) of fungal cajanol was investigated in vitro.Conclusions: First, a novel endophyte Hypocrea lixii, producing anticancer agent cajanol, was isolated from the host pigeon pea (Cajanus cajan [L.] Millsp.). Fungal cajanol possessed stronger cytotoxicity activity towards A549 cells in time-and dose-dependent manners.Significance and Impact of the Study: This endophyte is a potential handle for scientific and commercial exploitation, and it could provide a promising alterative approach for large-scale production of cajanol to satisfy new anticancer drug development.

The reaction of alkoxides with boron trichloride results in the generation of cations in the absence of Brønsted acids. The absence of a Brønsted acid can make a difference in subsequent transformations such as allylation reactions.

A novel strategy combining the advantages of polymer-supports and organotrifluoroborate chemistry for radiotracer preparation is reported.

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The first palladium-catalyzed reductive phenylation of norbornene (1) was published by Larock and Johnson [1] in 1989; since then the high synthetic potential of the hydroarylation [2] and especially its asymmetric variant [3] with bicyclic alkenes for the one-step construction of three asymmetric centers has induced a line of follow-up papers. This situation is especially true for the hydroarylation of the 7-aza-and oxabicyclic alkenes 2 (Scheme 1) [2b±d, 3c] as this synthetic route even in the case of the asymmetric pathway leads directly to the biologically highly active alkaloid Epibatidine [4] and its analogues.As we are interested in both the hydroarylation of bicyclic alkenes and, herein, in the use of these products in the stereoselective synthesis of substituted cyclopentane derivatives, we have investigated the hydroarylation followed by reductive cleavage of the easily accessible [5] 2,3-diazabicyclo[2.2.1]heptenes 3, [6] in which the N À N [7] or C À N bond [8] represents an internal point of fracture.Recently, we have reported the first palladium-catalyzed hydroarylation of the N,N'-diethoxycarbonyl-substituted derivative 4 of 3 with triethylamine as a base. [6] The following selective NÀN bond cleavage opens a highly stereoselective way to the trans-4-aryl-cis-1,3-diaminocyclopentanes 6 (Scheme 2).Encouraged by this initial result, we turned to the hydroarylation of the sterically more hindered and more rigid, trior tetracyclic Diels±Alder adducts of 1,3-cyclopentadiene with the very reactive azodienophiles 4-phenyl-1,2,4-triazoline-3,5-dione (7 a) and 2,3-phthalazine-1,4-dione (7 b). The reaction of 7 a with iodobenzene was chosen as a model system with which to optimize the reaction conditions; selected experiments are shown in Table 1.We started with the reaction conditions (Et 3 N, DMF, 65 8C, entry 1) which were optimal in case of the hydroarylation of 4; besides 21 % of the expected hydroarylation product 8 a, compound 9 a was formed in 9 % as the product of a CÀN cleavage reaction. Formally, the formation of 9 a is the result of a 1,2-hydrazidoarylation on the primarily employed 1,3-cyclopentadiene. From the 1 H and 13 C NMR spectroscopic data it appeared that the trans isomer 9 a was formed exclusively. The structural assignment is difficult in case of five-membered ring systems; however, the stereochemistry was unambiguously supported by an X-ray analysis (Figure 1). [9,10] COMMUNICATIONS

A boron trihalide mediated alkyne-aldehyde coupling reaction leading to stereodefined 1,3,5-triaryl-1,5-dihalo-1,4-pentadienes is described. The study led to the discovery of a direct substitution of hydroxyl groups by stereodefined alkenyl moieties using alkenylboron dihalides. During the investigation, it was also discovered that, at low temperatures, the reaction of BCl3 with alkynes produces monovinylboron dichloride rather than the reported divinylboron chloride. A modified reaction mechanism for the boron trichloride mediated alkyne-aldehyde coupling reaction is now proposed. The reaction temperature and mode of addition have been found to have dramatic affects on the stereochemistry of the diene products.