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Synthesis of a des-B-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core.

ABSTRACT: 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 displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biological function in cells. These studies shed new light on the role of the bryostatin B-ring in conferring bryo-like biological function to bryostatin analogues.

SUBMITTER: Kraft MB

PROVIDER: S-EPMC4183620 | biostudies-literature | 2014 Sep

REPOSITORIES: biostudies-literature

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Synthesis of a des-B-ring bryostatin analogue leads to an unexpected ring expansion of the bryolactone core.

Kraft Matthew B MB Poudel Yam B YB Kedei Noemi N Lewin Nancy E NE Peach Megan L ML Blumberg Peter M PM Keck Gary E GE

Journal of the American Chemical Society 20140910 38

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 displaying bryostatin-like biological function, the des-B-ring analogues displayed a phorbol-like biologica ...[more]

PMID: 25207434

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