Translating Nature’s Library: The Bryostatins and Function‐Oriented Synthesis
Tóm tắt
We review in part our computational, design, synthesis, and biological studies on a remarkable class of compounds and their designed analogs that have led to preclinical candidates for the treatment of cancer, a first‐in‐class approach to Alzheimer’s disease, and a promising strategy to eradicate HIV/AIDS. Because these leads target, in part, protein kinase C (PKC) isozymes, they have therapeutic potential even beyond this striking set of therapeutic indications. This program has given rise to new synthetic methodology and represents an increasingly important direction of synthesis focused on achieving function through synthesis‐informed design (function‐oriented synthesis).
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Tài liệu tham khảo
For pertinent discussions see:
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Anastas P. T., 1998, Green Chemistry Theory and Practice
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For some recent examples see:
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For current clinical information see:http://clinicaltrials.gov;
For reviews of PKC see:
For recent reviews of synthetic approaches to the bryostatins see:
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For additional and impressive examples of this dioxane design opportunity see:
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J. L. Baryza Ph.D. Dissertation Stanford University Stanford CA 2005.
Prepared in one step from ethyl acetoacetate.
Prepared in 4 steps and ∼95 % ee from acrolein and benzyl alcohol using an asymmetric allylation to set the C3 configuration.
For applications of ring closing metathesis processes in total synthesis see:
For recent reviews of applications of the Prins reaction and cyclization see:
For application of this reagent in bryostatin and analog synthesis see refs. [36] [38] and [42];
For several recent examples see: