Cryptomoscatone D2

Abrogation of ionizing radiation-induced G2 checkpoint and inhibition of nuclear export by Cryptocarya pyrones.[Pubmed:17440726]

Cancer Chemother Pharmacol. 2008 Mar;61(3):407-13.

G(2) checkpoint inhibitors can force cells arrested in G(2) phase by DNA damage to enter mitosis. In this manner, several G(2) checkpoint inhibitors can enhance killing of cancer cells by ionizing radiation and DNA-damaging chemotherapeutic agents, particularly in cells lacking p53 function. All G(2) checkpoint inhibitors identified to date target protein phosphorylation by inhibiting checkpoint kinases or phosphatases. Using a phenotypic cell-based assay for G(2) checkpoint inhibitors, we have screened a large collection of plant extracts and identified Z-Cryptofolione and Cryptomoscatone D2 as highly efficacious inhibitors of the G(2) checkpoint. These compounds and related pyrones also inhibit nuclear export. Leptomycin B, a potent inhibitor of Crm1-mediated nuclear export, is also a very potent G(2) checkpoint inhibitor. These compounds possess a reactive Michael acceptor site and do not appear promising as a radiosensitizing agents because they are toxic to unirradiated cells at checkpoint inhibitory concentrations. Nevertheless, the results show that inhibition of nuclear export is an alternative to checkpoint kinase inhibition for abrogating the G(2) checkpoint and they should stimulate the search for less toxic nuclear export inhibitors.

The first stereoselective total synthesis of (Z)-cryptomoscatone D2, a natural G(2) checkpoint inhibitor.[Pubmed:22405831]

Bioorg Med Chem Lett. 2012 Apr 1;22(7):2415-7.

The first stereoselective synthesis of (Z)-Cryptomoscatone D2, a naturally occurring G(2) checkpoint inhibitor, was accomplished using propane-1,3-diol as the starting material. The Maruoka asymmetric allylation, ring closing metathesis and the hydrogenation of the triple bond employing Lindlar's catalyst were involved as the key steps.