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The mammalian mel‐18/bmi‐1 gene products share an amino acid sequence and a secondary structure, including a RING‐finger motif, with the Drosophila Polycomb group (PcG) gene products Psc and Su(z)2, implying that they represent a gene family with related functions. As Drosophila PcG gene products are thought to function as transcriptional repressors by modifying chromatin structure, Mel‐18/Bmi‐1 might be expected to have similar activities. Here we have analyzed the function of mel‐18 and found that Mel‐18 acts as a transcriptional repressor via its target DNA sequence, 5′‐GACTNGACT‐3′. Interestingly, this binding sequence is found within regulatory or non‐coding regions of various genes, including the c‐myc, bcl‐2 and Hox genes, suggesting diverse functions of mel‐18 as the mammalian homolog of the PcG gene. We also demonstrate that mel‐18 has tumor suppressor activity, in contrast to bmi‐1, which has been defined as a proto‐oncogene.

The first examples of catalytic enantioselective ring-opening/cross-metathesis (EROCM) reactions that involve enol ethers are reported. Specifically, we demonstrate that catalytic EROCM of several oxa- and azabicycles, cyclobutenes and a cyclopropene with an alkyl- or aryl-substituted enol ether proceed readily in the presence of a stereogenic-at-Mo monopyrrolide-monoaryloxide. In some instances, as little as 0.15 mol % of the catalytically active alkylidene is sufficient to promote complete conversion within 10 minutes. The desired products are formed in up to 90% yield and >99:1 enantiomeric ratio (er) with the disubstituted enol ether generated in >90% Z selectivity. The enol ether of the enantiomerically enriched products can be easily differentiated from the terminal alkene through a number of functionalization procedures that lead to the formation of useful intermediates for chemical synthesis (e.g., efficient acid hydrolysis to afford the enantiomerically enriched carboxaldehyde). In certain cases, enantioselectivity is strongly dependent on enol ether concentration: larger equivalents of the cross partner leads to the formation of products of high enantiomeric purity (versus near racemic products with one equivalent). The length of reaction time can be critical to product enantiomeric purity; high enantioselectivity in reactions that proceed to >98% conversion in as brief a reaction time as 30 seconds can be nearly entirely eroded within 30 minutes. Mechanistic rationale that accounts for the above characteristics of the catalytic process is provided.