A streamlined total synthesis of N(14)-desacetoxytubulysin H (Tb1) based on a C-H activation strategy and a short total synthesis of pretubulysin D (PTb-D43) are described. Applications of the developed synthetic strategies and technologies to the synthesis of a series of tubulysin analogues (Tb2-Tb41 and PTb-D42) are also reported. Biological evaluation of the synthesized compounds against an array of cancer cells revealed a number of novel analogues (e.g., Tb14), some with exceptional potencies against certain cell lines [e.g., Tb32 with IC50 = 12 pM against MES SA (uterine sarcoma) cell line and 2 pM against HEK 293T (human embryonic kidney) cell line], and a set of valuable structure-activity relationships. The highly potent cytotoxic compounds discovered in this study are highly desirable as payloads for antibody-drug conjugates and other drug delivery systems for personalized targeted cancer chemotherapies.

Management practices to minimise soil erosion can be effectively carried out if the magnitude and the spatial distribution of soil erosion risk areas are known. Prioritisation of soil erosion risk areas is a challenging task, especially in the developing countries because of non‐availability of relevant data and analytical tools for such an assessment. As a result, it becomes difficult to establish appropriate soil conservation measures on the risk‐prone areas to reduce soil loss and ensure development of a sustainable management of soil resources. Such a database can be better generated and analysed in a geographical information system (GIS) environment to delineate and prioritise the soil erosion risk areas at state or regional level. Therefore, a methodology was developed to assess the soil erosion risks in eastern Himalayan region by integrating spatial data on prevailing erosion rates and soil loss tolerance limits in GIS environment. By comparing the potential erosion rates with permissible rates, we observed that about 58·94 per cent of total geographical area (TGA) of the region requires different degrees of erosion management and 28·38 per cent of TGA falls under no treatment category because of higher values of permissible erosion limits. It can be successfully applied to assess and prioritise soil erosion risks in any region or country and identify best management practices to bring the erosion losses within the permissible limits. Copyright © 2011 John Wiley & Sons, Ltd.

From the enediyne class of antitumor antibiotics, uncialamycin is among the rarest and most potent, yet one of the structurally simpler, making it attractive for chemical synthesis and potential applications in biology and medicine. In this article we describe a streamlined and practical enantioselective total synthesis of uncialamycin that is amenable to the synthesis of novel analogues and renders the natural product readily available for biological and drug development studies. Starting from hydroxy- or methoxyisatin, the synthesis features a Noyori enantioselective reduction, a Yamaguchi acetylide-pyridinium coupling, a stereoselective acetylide-aldehyde cyclization, and a newly developed annulation reaction that allows efficient coupling of a cyanophthalide and a p-methoxy semiquinone aminal to forge the anthraquinone moiety of the molecule. Overall, the developed streamlined synthesis proceeds in 22 linear steps (14 chromatographic separations) and 11% overall yield. The developed synthetic strategies and technologies were applied to the synthesis of a series of designed uncialamycin analogues equipped with suitable functional groups for conjugation to antibodies and other delivery systems. Biological evaluation of a select number of these analogues led to the identification of compounds with low picomolar potencies against certain cancer cell lines. These compounds and others like them may serve as powerful payloads for the development of antibody drug conjugates (ADCs) intended for personalized targeted cancer therapy.

The deficiency of robust and practical methods for 18F-radiofluorination is a bottleneck for positron emission tomography (PET) tracer development. Here, we report the first transition-metal-assisted 18F-deoxyfluorination of phenols. The transformation benefits from readily available phenols as starting materials, tolerance of moisture and ambient atmosphere, large substrate scope, and translatability to generate doses appropriate for PET imaging.