Cyclopentenones, bioactive

The groups of Liebeskind and Moore independently explored the ring expansion of allenyl-substituted cyclobutenol derivatives. This allows either the preparation of 5-alkylidene-2-cyclopentenones, which are substructures of naturally occurring bioactive compounds [59], or the generation of o-quinone methides, which are very attractive intermediates in the synthesis of hexahydrocannabinols [109]. As shown in Scheme 8.42, the ring expansion of the tetrasubstituted methoxyallene derivative 170 furnished the vinylhydroquinone 172 in high yield [109]. 

Weidler M, Rether J, Anke T, Erkel G, Sterner O (2001) New Bioactive Cyclopentenone Derivatives as Inhibitors of the IL-6 Dependent Signal Transduction. J Antibiot 54 679... 

The chemical reactivity of cyclopentenone IsoPs suggested that these compounds might be biologically active. The recent synthesis of two cyclopentenone IsoPs regioisomers, 15-A2-IsoP and 15-12-IsoP, has allowed us to examine their bioactivity. Studies employing primary cortical neuronal cultures demonstrated that both I5-A2-IS0P and 15-J2-IsoP potently induce neuronal apoptosis and exacerbate neurodegeneration caused by other insults at concentrations as low as 100 nM (19). These... 

Musiek ES, Breeding RS, Milne GL, Zanoni G, Morrow JD, McLaughlin B. Cyclopentenone isoprostanes are novel bioactive products of lipid oxidation which enhance neurodegeneration. J. Neurochem. 2006 97 1301. 

Enantioselective ring opening of epoxides was attained with (salen)Cr(III) complex (191) [68]. Cyclopentene derivatives (190) were converted with Me3SiN3 to azide-alcohols (192) in 80-90% yields up to 98% ee (Scheme 16.56). Kinetic resolution of racemic styrene oxide was performed in 98% ee. This reaction was applied to practical synthesis of enantiopure cyclic 1,2-aminoalcohols by reduction of the azide products by Pt02-catalyzed hydrogenation [69], to synthesis of cyclopentenone derivatives [70] to formal synthesis of bioactive compound Balanol [71], and to solid-phase synthesis of peptides [72]. 

The a-methylene cyclopentenones of the side products are also often found in natural products as bioactive moieties. In the absence of nucleophiles, the a-exo-methylene products become the major products. When the Nazarov reaction with 134 is carried out in the presence of ferf-butanol, which is expected to displace the other nucleophile, the exo-methylene cyclopentenone 135 is produced as a major product (Fig. 48). 

---