Synthesis of a library of tricyclic azepinoisoindolinones

• Bettina Miller,
• Shuli Mao,
• Kara M. George Rosenker,
• Joshua G. Pierce and
• Peter Wipf

Beilstein J. Org. Chem. 2012, 8, 1091–1097, doi:10.3762/bjoc.8.120

• . When the RCM reaction of 7 was conducted on larger scale in the absence of Ti(OiPr)4, and the crude intermediate was subjected to m-CPBA oxidation, epoxy alcohol 6 was isolated in 11% overall yield. LC–MS as well as NMR analyses suggested a 5:1 ratio of epimers at the hemiacetal carbon. Hydroxylation

Recent advances towards azobenzene-based light-driven real-time information-transmitting materials

• Jaume García-Amorós and
• Dolores Velasco

Beilstein J. Org. Chem. 2012, 8, 1003–1017, doi:10.3762/bjoc.8.113

• azophenol 10 (type-II). Solvent effect on the thermal relaxation time at 298 K, τ, for the type-II ortho-substituted azophenols 14–16. Cooperative effect of the para- and ortho-hydroxyl groups in azophenol 17. Effect of the poly-hydroxylation of the azobenzene core on the thermal relaxation time at 298 K, τ

Synthesis and antifungal properties of papulacandin derivatives

• Marjolein van der Kaaden,
• Eefjan Breukink and
• Roland J. Pieters

Beilstein J. Org. Chem. 2012, 8, 732–737, doi:10.3762/bjoc.8.82

• synthesis assay) but cannot reach the target site of C. albicans [12]. The same is true for the hydrogenated form of papulacandin D [12]. Clearly some form of unsaturation is needed to maintain biological activity, but it is not known to what extent unsaturation (and alkylation and/or hydroxylation) needs

Phytoalexins of the Pyrinae: Biphenyls and dibenzofurans

• Cornelia Chizzali and
• Ludger Beerhues

Beilstein J. Org. Chem. 2012, 8, 613–620, doi:10.3762/bjoc.8.68

• of the BIS reaction, 3,5-dihydroxybiphenyl, undergoes O-methylation to give 3-hydroxy-5-methoxybiphenyl (1), as recently detected in elicitor-treated S. aucuparia cell cultures (Khalil and Beerhues, unpublished). Subsequent 4-hydroxylation and additional O-methylation yield noraucuparin (2) and

Regio- and stereoselective oxidation of unactivated C–H bonds with Rhodococcus rhodochrous

• Elaine O’Reilly,
• Suzanne J. Aitken,
• Gideon Grogan,
• Paul P. Kelly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2012, 8, 496–500, doi:10.3762/bjoc.8.56

• Chemistry, University of York, Heslington, York, YO10 5DD, UK, Tel: +44 (0)1904 328256 10.3762/bjoc.8.56 Abstract The ability of Rhodococcus rhodochrous (NCIMB 9703) to catalyse the regio- and stereoselective hydroxylation of a range of benzyloxy-substituted heterocycles has been investigated. Incubation

• isomers in yields of up to 26%. Most interestingly, 2-(4-nitrobenzyloxy)tetrahydrofuran and 2-(4-nitrobenzyloxy)tetrahydropyran were transformed in high yields to the 4-hydroxylated and 5-hydroxylated products, respectively. Keywords: biocatalysis; cytochrome P450; hydroxylation; Rhodococcus rhodochrous

• hydrocarbons, including n-alkanes and isoalkanes, and has been reported to catalyse the terminal hydroxylation of chloroalkanes and long-chain alkenes [13]. It has been suggested that this strain contains an alkane-inducible NADH-dependent hydroxylase that catalyses the oxidation of n-octane to 1-octanol [13

Biocatalytic hydroxylation of n-butane with in situ cofactor regeneration at low temperature and under normal pressure

• Svenja Staudt,
• Christina A. Müller,
• Jan Marienhagen,
• Christian Böing,
• Stefan Buchholz,
• Ulrich Schwaneberg and
• Harald Gröger

Beilstein J. Org. Chem. 2012, 8, 186–191, doi:10.3762/bjoc.8.20

• Aachen, Germany Evonik Oxeno GmbH, Paul-Baumann-Straße 1, 45772 Marl, Germany Evonik Degussa GmbH, Industrial Chemicals, Paul-Baumann-Straße 1, 45772 Marl, Germany Faculty of Chemistry, Bielefeld University, Universitätsstraße 25, 33615 Bielefeld, Germany 10.3762/bjoc.8.20 Abstract The hydroxylation of

• n-alkanes, which proceeds in the presence of a P450-monooxygenase advantageously at temperatures significantly below room temperature, is described. In addition, an enzymatic hydroxylation of the “liquid gas” n-butane with in situ cofactor regeneration, which does not require high-pressure

• conditions, was developed. The resulting 2-butanol was obtained as the only regioisomer, at a product concentration of 0.16 g/L. Keywords: biotransformations; cofactor regeneration; green chemistry; hydroxylation; P450-monooxygenase; Introduction The (regioselective) oxidative functionalization of

Tertiary alcohol preferred: Hydroxylation of trans-3-methyl-L-proline with proline hydroxylases

• Christian Klein and
• Wolfgang Hüttel

Beilstein J. Org. Chem. 2011, 7, 1643–1647, doi:10.3762/bjoc.7.193

• oxidation of tertiary alkyl centers is a most-straightforward but challenging approach, since these positions are sterically hindered. In contrast to P450-monooxygenases, there is little known about the potential of non-heme iron(II) oxygenases to catalyze such reactions. We have studied the hydroxylation

• approach whose potential has not yet been fully exploited is the stereospecific hydroxylation of tertiary alkyl moieties with oxygenases. Most oxidations to tertiary alcohols described so far were observed during degradation of steroids and other terpenoid bioactive compounds by microbial whole cells [10

• stereospecific hydroxylation of trans-3-methyl-L-proline to (3R)-3-hydroxy-3-methyl-L-proline with two different proline hydroxylases. In contrast to the mechanistically related and more common prolyl hydroxylases, which accept peptide bound proline as a substrate and play a key role in collagen biosynthesis

Natural product biosyntheses in cyanobacteria: A treasure trove of unique enzymes

• Jan-Christoph Kehr,
• Douglas Gatte Picchi and
• Elke Dittmann

Beilstein J. Org. Chem. 2011, 7, 1622–1635, doi:10.3762/bjoc.7.191

• responsible for uracil ring formation, although biochemical evidence is currently missing. The final hydroxylation step towards cylindrospermopsin has been shown to be catalyzed by CyrI, a 2-oxoglutarate-dependent iron oxygenase [31]. Interestingly, two epimers were described for the corresponding hydroxyl

Chimeric self-sufficient P450cam-RhFRed biocatalysts with broad substrate scope

• Aélig Robin,
• Valentin Köhler,
• Alison Jones,
• Afruja Ali,
• Paul P. Kelly,
• Elaine O'Reilly,
• Nicholas J. Turner and
• Sabine L. Flitsch

Beilstein J. Org. Chem. 2011, 7, 1494–1498, doi:10.3762/bjoc.7.173

• ; P450 monooxygenase; substrate engineering; Introduction P450 monooxygenases are a ubiquitous family of enzymes found in a wide variety of organisms in all domains of life. These enzymes catalyse oxidation reactions such as hydroxylation, epoxidation, N- and O-dealkylation and heteroatom oxidation

• . Surprisingly, compound 7c, bearing a protecting group very similar to Boc, showed mainly hydroxylation of an unactivated carbon atom of the protecting group. Mutant P450cam(Y96F)-RhFRed displayed similar results to the Y96A mutant, albeit with lower conversions. The double mutant P450cam(Y96F/V247A)-RhFRed

• the biotransformation reaction with P450cam(Y96A)-RhFRed, 13% with P450cam(Y96F)-RhFRed and 15% with P450cam(Y96F/V247A)-RhFRed. Similar studies were performed with compound 11 in order to find the combination of P450 mutant and protecting group with the highest hydroxylation conversion. Low

Combined directed ortho-zincation and palladium-catalyzed strategies: Synthesis of 4,n-dimethoxy-substituted benzo[b]furans

• Verónica Guilarte,
• M. Pilar Castroviejo,
• Estela Álvarez and
• Roberto Sanz

Beilstein J. Org. Chem. 2011, 7, 1255–1260, doi:10.3762/bjoc.7.146

• benzo[b]furan derivatives has been developed from 3-halo-2-iodoanisoles bearing an additional methoxy group, which have been accessed through an ortho-zincation/iodination reaction. Two palladium-catalyzed processes, namely a Sonogashira coupling followed by a tandem hydroxylation/cyclization sequence

• Sonogashira coupling and a tandem hydroxylation/heterocyclization reaction. The required o-dihaloanisole derivatives could be prepared by a selective ortho-metallation reaction and subsequent electrophilic quenching with iodine (Scheme 1). Results and Discussion As established in our proposed retrosynthetic

• heterocyclization. In recent years, the direct hydroxylation of aryl halides has been developed by several groups by using palladium- or copper-catalyzed protocols. Whereas the reactions under copper catalysis work well for aryl iodides [45][46][47][48], the palladium-catalyzed hydroxylation also takes place with

Gold-catalyzed heterocyclizations in alkynyl- and allenyl-β-lactams

• Benito Alcaide and
• Pedro Almendros

Beilstein J. Org. Chem. 2011, 7, 622–630, doi:10.3762/bjoc.7.73

• oxycyclization/hydroxylation of 2-azetidinone-tethered alkynols for the synthesis of non-fused, spiro, and fused oxabicyclic β-lactams has been reported [65]. Attempts at a cyclization reaction of terminal alkynols using gold catalysts failed. However, under the appropriate reaction conditions was found that

• AuCl3 could be a good catalyst for the cycloetherification reaction of non-terminal alkynols 22. Scheme 12 shows that tetrahydrofuryl hemiacetals 23 are accessible as single isomers in fair yields via the gold-catalyzed tandem oxycyclization/hydroxylation reaction of 2-azetidinone-tethered

• scope of these transformations, gold-catalyzed heterocyclization reactions of alkynols to the fused bicyclic systems was also examined. Indeed, treatment of 2-azetidinone-tethered bishomopropargylic alcohol 26 with AuCl3 provided the desired cycloetherification/hydroxylation product 27a in good yield

Synthesis of a new class of aminocyclitol analogues with the conduramine D-2 configuration

• Latif Kelebekli,
• Yunus Kara and
• Murat Celik

Beilstein J. Org. Chem. 2010, 6, No. 15, doi:10.3762/bjoc.6.15

• acetic anhydride/CH3COONa [35] (Scheme 3). Careful examination of the reaction mixture did not reveal the formation of the other isomer. The stereochemical course of the hydroxylation may be syn or anti with respect to the oxazolidinone and cyclobutane rings. NMR spectroscopic studies did not allow the

• assignment of the exact orientation of the hydroxyl groups. X-ray analysis of 18 (Figure 1) revealed the exact configuration of the compound. This also confirms the configurations of endoperoxide 10, oxazolidinone 13 and cis-hydroxylation product 17. The all cis-configuration of the four acetate and amino

• ionization (Scheme 5). Hydrolysis of oxazolidinone 23 with K2CO3 gave alcohol 26, which was subsequently converted into acetate 27 by treatment with Ac2O/NaOAc [35] (Scheme 6). cis-Hydroxylation of 27 with OsO4 at 0°C gave the corresponding diol 28, which was further converted into triacetate 7 with Ac2O

End game strategies towards the total synthesis of vibsanin E, 3-hydroxyvibsanin E, furanovibsanin A, and 3-O-methylfuranovibsanin A

• Brett D. Schwartz,
• Craig M. Williams and
• Paul V. Bernhardt

Beilstein J. Org. Chem. 2008, 4, No. 34, doi:10.3762/bjoc.4.34

• sidechain and corresponding α-oxo functionality depicted in Scheme 2. Essentially four areas were identified for study; 1) regio- and stereospecific α-hydroxylation (methoxylation) 19, 2) furan formation i.e. 20, 3) installing the acetone sidechain i.e. 21, and 4) building the enol ester function i.e. 22

• (Scheme 2). The results of each area of investigation allow end game strategies to be postulated based on combinations of these results. For example, success with α-hydroxylation (methoxylation) 19 could flow into furan formation (i.e. 20), installing the acetone sidechain i.e. 21, or building the enol

• cleavage. Nevertheless, the acetone sidechain could be introduced in ~20% overall yield allowing end game functionalisation (as discussed below). α-Hydroxylation was next investigated. Considering the observed preference for regiospecific enolate formation in our system we devised a simple two pot

Sordarin, an antifungal agent with a unique mode of action

• Huan Liang

Beilstein J. Org. Chem. 2008, 4, No. 31, doi:10.3762/bjoc.4.31

• protection of the alcohol, MoO5-mediated hydroxylation of the enolate of the ester [22] and ensuing dehydration by SOCl2 (Scheme 2). The sequence utilized for the introduction of the dienophilic subunit in 13 is outlined in Scheme 3. The primary alcohol was deprotected (TBAF) and oxidized to an aldehyde