The development of a stereoselective total synthesis of β-dihydroagarofuran 4 is described. This compound contains the same oxygenation pattern on its 'lower-rim' as found in the natural sesquiterpene (-)-euonyminol (1) and it is expected that the route described should be applicable to the synthesis of that complex natural product. (-)-Euonyminol is found as the core scaffold of a series of complex macrodilactone sesquiterpenoids isolated from the Celastraceae which possess interesting biological activities (e.g. anti-HIV activity). The synthetic route builds upon an epoxidative asymmetric desymmetrisation of meso-diallylic alcohol 10 that we have reported previously. It features a lactate Ireland-Claisen rearrangement to establish the quaternary stereocentre at C11 (27→28a) and an unusual dealkylative intramolecular epoxide-opening by the C11 methyl ether to establish the tetrahydrofuranyl C-ring of the β-dihydroagarofuran skeleton (35→36).

The diastereoselectivity of the Rh-catalyzed C-H amination was examined with 18 chiral open-chain substrates, which bear a benzylic methylene group in the α-position to a stereogenic center (-CHMeX), and with four chiral cyclic tetralins, in which the stereogenic center was positioned at carbon atom C2. The C-H amination was performed using trichloroethoxysulfonyl-substituted amine (H(2)NTces) as the nitrogen source, a diacyloxyiodobenzene as the oxidant, and bis[rhodium(α,α,α',α'-tetramethyl-1,3-benzenedipropionate)] [Rh(2)(esp)(2)] as the catalyst. For acyclic substrates a high syn diastereoselectivity (dr > 95/5) was found if the substituent X was Br, PO(OEt)(2), SO(2)Ph, or OOCCF(3) (eight examples). Moderate to good syn selectivities (dr = 80/20 to 91/9) were found for X = NO(2), OAc, COOMe, and CN (eight examples). Only two substrates gave a low diastereoselectivity. Kinetic isotope effect (KIE) experiments revealed that there is no secondary KIE when replacing -CHMeCOOMe by -CDMeCOOMe, but there is a significant primary KIE at the benzylic methylene position (4.8 ± 0.7). Deuteration experiments provided evidence that the reaction proceeds stereospecifically with retention of configuration. A preferred conformation is proposed, which explains the outcome of the reaction. In this conformation the X substituent is antiperiplanar to the C-H bond, which is diastereoselectively attacked, and steric strain between the remaining substituents at the stereogenic and the prostereogenic center is minimized. DFT calculations support this model. They suggest, however, that the reaction is not concerted but occurs via hydrogen atom abstraction and subsequent radical rebound. Further support for an antiperiplanar attack relative to a given substituent X = Br, COOMe, or CN was obtained with the respective 2-substituted tetralins. Attack at C1 provides almost exclusively the trans-amination product. If the size of the X substituent increases [Br < CN < COOMe < PO(OEt)(2)], attack at the carbon atom C4 prevails, delivering the respective trans-amination products at this position.

The African slender lungfish, Protopterus dolloi, is highly adapted to withstand periods of drought by secreting a mucous cocoon and estivating for periods of months to years. Estivation is similar to the diapause and hibernation of other animal species in that it is characterized by negligible activity and a profoundly depressed metabolic rate. As is typically observed in quiescent states, estivating P. dolloi are resistant to environmental stresses. We tested the hypothesis that P. dolloi enhances stress resistance during estivation by upregulating intracellular antioxidant defences in brain and heart tissues. We found that most of the major intracellular antioxidant enzymes, including the mitochondrial superoxide dismutase, cytosolic superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, were upregulated in brain tissue of lungfish that had estivated for 60 days. Several of these enzymes were also elevated in heart tissue of estivators. These changes wer... Abstract The African slender lungWsh, Protopterus dolloi, is highly adapted to withstand periods of drought by secreting a mucous cocoon and estivating for periods of months to years. Estivation is similar to the diapause and hibernation of other animal species in that it is characterized by negligible activity and a profoundly depressed metabolic rate. As is typically observed in quiescent states, estivating P. dolloi are resistant to environmental stresses. We tested the hypothesis that P. dolloi enhances stress resistance during estivation by upregulating intracellular antioxidant defences in brain and heart tissues. We found that most of the major intracellular antioxidant enzymes, including the mitochondrial superoxide dismutase, cytosolic superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase, were upregulated in brain tissue of lungWsh that had estivated for 60 days. Several of these enzymes were also elevated in heart tissue of estivators. These changes were not due to food deprivation, as they did not occur in a group of Wsh that were deprived of food but maintained in water for the same period of time. We found little evidence of tissue oxidative damage in estivators. Products of lipid peroxidation (4-hydroxynonenal adducts) and oxidative protein damage (carbonylation) were similar in estivating and control lungWsh. However, protein nitrotyrosine levels were elevated in brain tissue of estivators. Taken together, these data indicate that estivating P. dolloi have enhanced oxidative stress resistance in brain and heart due to a signiWcant upregulation of intracellular antioxidant capacity.

A continuous packed bed reactor for NADH-dependent biocatalysis using enzymes co-immobilized on a simple carbon support was optimized to 100% conversion in a residence time of 30 min. Conversion of pyruvate to lactate was achieved by co-immobilized lactate dehydrogenase and formate dehydrogenase, providing in situ cofactor recycling. Other metrics were also considered as optimization targets, such as low E factors between 2.5–11 and space-time yields of up to 22.9 g L –1 h –1 . The long-term stability of the biocatalytic reactor was also demonstrated, with full conversion maintained over more than 30 h of continuous operation.

The first synthesis of hydroxy-iso-evoninic acid (2), a pyridyl diacid found as a macrodilactone bridging ligand in bioactive Celastraceae sesquiterpenoid-based natural products, has been achieved in 9 steps and an overall yield of 26%. The synthesis utilizes a benzilic ester rearrangement (BER) and a late stage benzylic oxidation to give access to all four stereoisomers whose absolute stereochemistry was assigned following chromatographic separation and anomalous dispersion X-ray crystallography.

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Progress towards the asymmetric total synthesis of (-)-euonyminol is described with the focus on the installation of the oxygenation pattern on the lower rim of the molecule. An IrelandClaisen rearrangement/lactonisation cascade has been developed and studies towards further elaboration have uncovered an intriguing tunable diastereoselective a-bromination of the resulting g-lactone.

Stereocontrolled Formation of Styrenes by Pd(0)-Catalyzed Cross-Coupling of Photoactivated (E)-Alkenylgermanes with Aryl Bromides. -The use of PCy3.HBF4 instead of P(o-tolyl)3 gives higher (E)-selectivity, cf. the reaction of the compound (Ia) with the compound (IIf). The germanes (I) bear a fluorous tag to facilitate purification by fluorous solid-phase extraction. -(TSENG, C.-C.; LI, M.; MO, B.; WARREN, S. A.; SPIVEY*, A. C.; Chem. Lett. 40 (2011) 9, 995-997, http://dx.