Mar. Drugs 2010, 8(1), 122-172; doi:10.3390/md80100122
Review

Calyculins and Related Marine Natural Products as Serine- Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C

email, email and * email
Received: 21 December 2009; in revised form: 12 January 2010 / Accepted: 13 January 2010 / Published: 21 January 2010
(This article belongs to the Special Issue Synthesis around Marine Natural Products)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Calyculins, highly cytotoxic polyketides, originally isolated from the marine sponge Discodermia calyx by Fusetani and co-workers, belong to the lithistid sponges group. These molecules have become interesting targets for cell biologists and synthetic organic chemists. The serine/threonine protein phosphatases play an essential role in the cellular signalling, metabolism, and cell cycle control. Calyculins express potent protein phosphatase 1 and 2A inhibitory activity, and have therefore become valuable tools for cellular biologists studying intracellular processes and their control by reversible phosphorylation. Calyculins might also play an important role in the development of several diseases such as cancer, neurodegenerative diseases, and type 2-diabetes mellitus. The fascinating structures of calyculins have inspired various groups of synthetic organic chemists to develop total syntheses of the most abundant calyculins A and C. However, with fifteen chiral centres, a cyano-capped tetraene unit, a phosphate-bearing spiroketal, an anti, anti, anti dipropionate segment, an α-chiral oxazole, and a trihydroxylated γ-amino acid, calyculins reach versatility that only few natural products can surpass, and truly challenge modern chemists’ asymmetric synthesis skills.
Keywords: marine natural products; total synthesis; protein phosphatase inhibitors
PDF Full-text Download PDF Full-Text [2365 KB, uploaded 21 January 2010 11:24 CET]

Export to BibTeX |
EndNote


MDPI and ACS Style

Fagerholm, A.E.; Habrant, D.; Koskinen, A.M.P. Calyculins and Related Marine Natural Products as Serine- Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C. Mar. Drugs 2010, 8, 122-172.

AMA Style

Fagerholm AE, Habrant D, Koskinen AMP. Calyculins and Related Marine Natural Products as Serine- Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C. Marine Drugs. 2010; 8(1):122-172.

Chicago/Turabian Style

Fagerholm, Annika E.; Habrant, Damien; Koskinen, Ari M. P. 2010. "Calyculins and Related Marine Natural Products as Serine- Threonine Protein Phosphatase PP1 and PP2A Inhibitors and Total Syntheses of Calyculin A, B, and C." Mar. Drugs 8, no. 1: 122-172.

Mar. Drugs EISSN 1660-3397 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert