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Total Synthesis Of The Bryostatins
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Book Synopsis Total Synthesis of the Bryostatins by : Percy Hudson Carter
Download or read book Total Synthesis of the Bryostatins written by Percy Hudson Carter and published by . This book was released on 1998 with total page 850 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Studies Directed Towards the Total Synthesis of Bryostatins by : David Milburn Robinson
Download or read book Studies Directed Towards the Total Synthesis of Bryostatins written by David Milburn Robinson and published by . This book was released on 1990 with total page 56 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Towards the Total Synthesis of Bryostatins by : Peter Green
Download or read book Towards the Total Synthesis of Bryostatins written by Peter Green and published by . This book was released on 2010 with total page 202 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Towards the Total Synthesis of Bryostatins by : Peter Green
Download or read book Towards the Total Synthesis of Bryostatins written by Peter Green and published by . This book was released on 2010 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Approaches Towards the Total Synthesis of the Bryostatins by : Matthew O'Brien
Download or read book Approaches Towards the Total Synthesis of the Bryostatins written by Matthew O'Brien and published by . This book was released on 2002 with total page 169 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Total Synthesis of Bryostatin 7 by : John Charles Roberts
Download or read book The Total Synthesis of Bryostatin 7 written by John Charles Roberts and published by . This book was released on 1991 with total page 338 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Studies Toward the Total Synthesis of Bryostatin 1 by : David Curtis Whritenour
Download or read book Studies Toward the Total Synthesis of Bryostatin 1 written by David Curtis Whritenour and published by . This book was released on 1988 with total page 608 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Synthetic Efforts Toward the Total Synthesis of Bryostatin 1 Emphasis on the C17-C27 Fragment by : Victoria Lynn Wilde
Download or read book Synthetic Efforts Toward the Total Synthesis of Bryostatin 1 Emphasis on the C17-C27 Fragment written by Victoria Lynn Wilde and published by . This book was released on 2008 with total page 294 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Towards the Total Synthesis of Bryostatin 1 by : Seyed Hassan Seradj
Download or read book Towards the Total Synthesis of Bryostatin 1 written by Seyed Hassan Seradj and published by . This book was released on 2009 with total page 137 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Studies Directed Towards the Total Synthesis of Bryostatin by : Erick Moran Carreira
Download or read book Studies Directed Towards the Total Synthesis of Bryostatin written by Erick Moran Carreira and published by . This book was released on 1990 with total page 352 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Efficient Access to Bryostatin and Functional Bryostatin Analogs by : Adam James Schrier
Download or read book Efficient Access to Bryostatin and Functional Bryostatin Analogs written by Adam James Schrier and published by . This book was released on 2011 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The bryostatins are a family of structurally complex natural products isolated from the marine bryozoan Bugula neritina. Bryostatin 1 is currently being investigated for cancer, Alzheimer's and HIV/AIDS indications. Despite these remarkable activities, research on the bryostatins is hampered by their low natural abundance. Efficient access by total chemical synthesis has been in large part precluded by the bryostatins' structural complexity. This dissertation describes the design, synthesis, and preliminary biological evaluation of functional bryostatin analogs that possess biological activities comparable or superior to the natural product. These fully synthetic analogs were convergently assembled in a uniquely step-economical manner using novel macrocyclization strategies, including macroacetalization and Prins-driven macrocyclization approaches. Bryostatin analogs were identified that possess unique affinities (subnanomolar) and selectivities for protein kinase C (PKC). Synthetic bryostatin analogs also exhibit subnanomolar antileukemic activity in in vitro assays. The convergent total synthesis of bryostatin 9, a highly potent congener of the natural product family, is also described.
Book Synopsis The Total Synthesis and Biological Evaluation of Bryostatin 1 and Its Analogues by : Yam Bahadur Poudel
Download or read book The Total Synthesis and Biological Evaluation of Bryostatin 1 and Its Analogues written by Yam Bahadur Poudel and published by . This book was released on 2011 with total page 534 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Scalable Total Synthesis of Bryostatin 1 Enables the Design, Synthesis, and Biological Evaluation of Bryostatin Analogs by : Clayton Thomas Hardman
Download or read book Scalable Total Synthesis of Bryostatin 1 Enables the Design, Synthesis, and Biological Evaluation of Bryostatin Analogs written by Clayton Thomas Hardman and published by . This book was released on 2020 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: Bryostatin 1 is a natural product that was originally isolated from the marine sponge Bugula neritina more than 50 years ago. Following its isolation, it has demonstrated unprecedented clinical potential across a number of indications, including HIV/AIDS eradication, the treatment of Alzheimer's disease and neurological disorders, and cancer immunotherapy. Despite this unique portfolio of indications, the natural supply of bryostatin 1 from its source organism is limited and variable and maintaining a consistent supply of the natural product has hindered its clinical advancement. To enable the continued clinical evaluation of bryostatin 1, we developed a scalable total synthesis of the natural product that can sustainably supply future clinical studies of this exciting clinical candidate. Despite its promising activity, bryostatin 1 is a marine natural product that is neither evolved nor optimized for the treatment of human disease. Historically, the scarcity of isolated material and the challenges associated with making modifications of the delicate and densely functionalized bryostatin skeleton have precluded efforts to optimize the biological activity of this natural product lead through derivatization and exploration of structure-activity relationships (SAR) around the macrocycle. Drawing on the synthetic platform we developed in our scalable synthesis of bryostatin 1, we accomplished the design, synthesis, and biological evaluation of the first close-in analogs of bryostatin 1. Using a function-oriented synthesis (FOS) strategy informed by a combination of computational and biological data surrounding bryostatin's interaction with its protein target, protein kinase C (PKC), we synthesized a series of bryostatin analogs designed to maintain PKC affinity while allowing for a systematic investigation of their biological function. By leveraging the modularity of our bryostatin 1 synthesis, we developed complementary late-stage diversification strategies that provide efficient synthetic access to parallel series of bryostatin analogs with modifications in the A- and B-rings. In agreement with our pharmacophore model, these new agents retain affinity for PKC but exhibit variable PKC translocation kinetics. We further demonstrate that select analogs potently induce increased cell surface expression of CD22, a promising target for the treatment of leukemias and lymphomas, in in vitro models of acute lymphoblastic leukemia (ALL) and AIDS-related lymphomas, highlighting the potential general use of bryostatin and bryostatin analogs for enhancing antigen-targeted cancer immunotherapies. Finally, bryostatin 1 has been shown to prevent progressive neurodegeneration in a mouse model of multiple sclerosis (MS). Working with Professors Paul Kim and Michael Kornberg at Johns Hopkins, we show that several bryostatin analogs replicate the anti-inflammatory effects of bryostatin 1 on innate immune cells in vitro and lead analog SUW133 attenuates neuroinflammation and prevents the development of MS-related neurological deficits in vivo. We further demonstrate that this activity is dependent on PKC. These findings identify bryostatin analogs as promising drug candidates for targeting innate immunity in neuroinflammation and create a platform for evaluation of synthetic PKC modulators for the treatment of MS and other neuroinflammatory diseases.
Book Synopsis Approaches Towards the Total Synthesis of the 20-deoxy Bryostatins by : Simon Hardy
Download or read book Approaches Towards the Total Synthesis of the 20-deoxy Bryostatins written by Simon Hardy and published by . This book was released on 2009 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis The Synthesis and Biological Evaluation of Structurally Simplified Bryostatin Analogues and the Total Synthesis of Swinholide A by : Matthew Brian Kraft
Download or read book The Synthesis and Biological Evaluation of Structurally Simplified Bryostatin Analogues and the Total Synthesis of Swinholide A written by Matthew Brian Kraft and published by . This book was released on 2011 with total page 396 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Approaches Towards the Total Synthesis of the 20-deoxy Bryostatins by : Simon Hardy
Download or read book Approaches Towards the Total Synthesis of the 20-deoxy Bryostatins written by Simon Hardy and published by . This book was released on 2009 with total page 206 pages. Available in PDF, EPUB and Kindle. Book excerpt:
Book Synopsis Synthetic Studies Directed Toward the Total Synthesis of Rhizoxin D and the Bryostatins by : Jonathan Aron Covel
Download or read book Synthetic Studies Directed Toward the Total Synthesis of Rhizoxin D and the Bryostatins written by Jonathan Aron Covel and published by . This book was released on 2006 with total page 424 pages. Available in PDF, EPUB and Kindle. Book excerpt: