Synthesis of ades-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core

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Synthesis of a des-B-Ring Bryostatin Analogue Leads to an Unexpected Ring Expansion of the Bryolactone Core

A convergent synthesis of a des-B-ring bryostatin analogue is described. This analogue was found to undergo an unexpected ring expansion of the bryolactone core to generate the corresponding 21-membered macrocycle. The parent analogue and the ring-expanded product both displayed nanomolar binding affinity for PKC. Despite containing A-ring substitution identical to that of bryostatin 1 and disp...

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The bryostatins are a family of marine natural products that display a wide range of biological activities, most notably their anticancer activity in vivo.1 This effect is attributed to their ability to modulate the functions of protein kinase C isozymes within cells. One of the members of this family, bryostatin 1, is currently in several phase I and phase II clinical trials for the treatment ...

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The seco-B-ring bryostatin analogue, macrodiolide WN-1, was prepared in 17 steps (longest linear sequence) and 30 total steps with three bonds formed via hydrogen-mediated C-C coupling. This synthetic route features a palladium-catalyzed alkoxycarbonylation of a C2-symmetric diol to form the C9-deoxygenated bryostatin A-ring. WN-1 binds to PKCα (Ki = 16.1 nM) and inhibits the growth of multiple...

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RESIDUAL OF IDEALS OF AN L-RING

The concept of right (left) quotient (or residual) of an ideal η by anideal ν of an L-subring μ of a ring R is introduced. The right (left) quotients areshown to be ideals of μ . It is proved that the right quotient [η :r ν ] of an idealη by an ideal ν of an L-subring μ is the largest ideal of μ such that[η :r ν ]ν ⊆ η . Most of the results pertaining to the notion of quotients(or residual) of ...

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ژورنال

عنوان ژورنال: Journal of the American Chemical Society

سال: 2014

ISSN: 0002-7863,1520-5126

DOI: 10.1021/ja5078188