Selective allylic hydroxylation of acyclic terpenoids by CYP154E1 from Thermobifida fusca YX

• Anna M. Bogazkaya,
• Clemens J. von Bühler,
• Sebastian Kriening,
• Alexandrine Busch,
• Alexander Seifert,
• Jürgen Pleiss,
• Sabine Laschat and
• Vlada B. Urlacher

Beilstein J. Org. Chem. 2014, 10, 1347–1353, doi:10.3762/bjoc.10.137

• catalyse either the allylic hydroxylation of alkenes or the epoxidation of the corresponding C=C double bond or produce a mixture of the respective allylic alcohols and epoxides. Chemo- and regioselectivity of such reactions depend on the structure of the substrate and P450 used [16]. Different P450

• mutants for the formation of C7-hydroxylated compound 11 as the main product. Variant V286L produced 44% of 7-hydroxygeranylactone (11) as well as the compounds 13 (18%) and 15 (35%). Substrate epoxidation leading to the epoxide 17 was much slower compared to the wild type: this product accounted to less

Heronapyrrole D: A case of co-inspiration of natural product biosynthesis, total synthesis and biodiscovery

• Jens Schmidt,
• Zeinab Khalil,
• Robert J. Capon and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2014, 10, 1228–1232, doi:10.3762/bjoc.10.121

• effect an epoxidation of 8. Application of substoichiometric amounts of oxidant (Oxone®) delivered the isomeric mono-epoxides 9 and 10 as the main constituents, along with minor amounts of the bis-epoxide 11. Of note, on work-up 9 was observed to undergo partial cyclization to the desired tetrahydrofuran

Amino acid motifs in natural products: synthesis of O-acylated derivatives of (2S,3S)-3-hydroxyleucine

• Oliver Ries,
• Martin Büschleb,
• Markus Granitzka,
• Dietmar Stalke and
• Christian Ducho

Beilstein J. Org. Chem. 2014, 10, 1135–1142, doi:10.3762/bjoc.10.113

• will also be useful for the synthesis of other natural products containing this amino acid. Several synthetic approaches towards (2S,3S)-3-hydroxyleucine have been established utilizing for instance diastereoselective aldol reactions [26][27][28], Sharpless epoxidation [29], asymmetric hydrogenation

Synthesis of (2S,3R)-3-amino-2-hydroxydecanoic acid and its enantiomer: a non-proteinogenic amino acid segment of the linear pentapeptide microginin

• Rajendra S. Rohokale and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2014, 10, 667–671, doi:10.3762/bjoc.10.59

• -groups to olefinic acid by either asymmetric epoxidation, dihydroxylation or aminohydroxylation [10][11][12][13][14][15], (ii) the asymmetric synthesis of β-lactams by a Staudinger reaction between ketene and imine to give the corresponding amino acids [16], and (iii) the Lewis acid catalyzed

Intermediates in monensin biosynthesis: A late step in biosynthesis of the polyether ionophore monensin is crucial for the integrity of cation binding

• Wolfgang Hüttel,
• Jonathan B. Spencer and
• Peter F. Leadlay

Beilstein J. Org. Chem. 2014, 10, 361–368, doi:10.3762/bjoc.10.34

• initially-formed (E,E,E)-triene undergoes stereospecific epoxidation to a tri-epoxide and subsequent ring-opening and cyclisation to generate the polyether rings. This model has been confirmed and extended (Scheme 1) by the results of more recent work in which specific genes have been disrupted or deleted

Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• in the formation of a bridged tetracycle after initial Heck coupling followed by carbo-palladation and subsequent β-hydride elimination [69][70][71]. Double bond regioisomers (between C7 & C8 or C13 & C14) were obtained. Oxidation with DDQ yielded the 1,6-unsaturated ketone 72. Selective epoxidation

• ). Deoxygenation with concomitant isomerization of the double bond according to Gevorgyan [100] was followed by epoxidation to provide barekoxide (106). Acid-catalyzed isomerization finally yielded barekol (107). Davies and coworkers [101][102][103] used the formal [4 + 3]-cycloaddition approach to access the

• ] applied the DVCPR in their total synthesis of gelsemine (146, see Scheme 20 and Scheme 21). Starting from bicycle 160 [140] epoxidation using mCPBA furnished epoxide 161 [141][142], which could be converted into vinylcyclopropanecarbaldehyde 162 upon rearrangement. Olefination using HWE-reagent 163

Synthesis of five- and six-membered cyclic organic peroxides: Key transformations into peroxide ring-retaining products

• Alexander O. Terent'ev,
• Dmitry A. Borisov,
• Vera A. Vil’ and
• Valery M. Dembitsky

Beilstein J. Org. Chem. 2014, 10, 34–114, doi:10.3762/bjoc.10.6

The difluoromethylene (CF₂) group in aliphatic chains: Synthesis and conformational preference of palmitic acids and nonadecane containing CF₂ groups

• Yi Wang,
• Ricardo Callejo,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2014, 10, 18–25, doi:10.3762/bjoc.10.4

• ketone 14 was treated with DAST. Conversion to the CF2 group occurred in modest (45%) yield. Generally aliphatic ketones are less efficiently converted to CF2 groups with DAST in comparison to propargylic ketones. Progression of the resultant CF2 containing olefin 15 by epoxidation, chain extension and

N,N'-(Hexane-1,6-diyl)bis(4-methyl-N-(oxiran-2-ylmethyl)benzenesulfonamide): Synthesis via cyclodextrin mediated N-alkylation in aqueous solution and further Prilezhaev epoxidation

• Julian Fischer,
• Simon Millan and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2834–2840, doi:10.3762/bjoc.9.318

• concentrations [10][11][12]. An alternative route is a two-step reaction via N-allylation and further Prilezhaev epoxidation with peroxides [13][14][15]. The solubility of hydrophobic reactants in water can be increased significantly by cyclodextrins (CD) and thereby the use of organic solvents can be reduced

• -methylbenzenesulfonamide) (3), as precursor for the subsequent N-alkylation and further Prilezhaev epoxidation, was synthesized easily from p-toluenesulfonyl chloride (1) and hexamethylenediamine (2) [23]. The resulting crystalline sulfonamide was first described in 1927 prepared from 1,6-dibromohexane and p

• moieties to the hydroxy functions is likely [2]). Synthesis of sulfonamide 3, N-alkylation of 3 in organic solution and of CD-complex (3β) in aqueous phase to obtain 5 and the subsequent epoxidation with m-chloroperbenzoic acid (mCPBA) to yield product 6. Cyclization of L-(+)-lysine monohydrochloride to

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• ]-Wittig rearrangement, a diastereoselective epoxidation, and a microwave assisted transannular epoxide opening reaction. It is also noteworthy that the starting material 55 contains an extraneous fluorine atom which is deleted during the synthetic sequence; this approach takes advantage of the often low

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• conjugate addition [93], and a recent synthesis of lucentamycin A was achieved using this strategy [94]. Epoxidation of A leads to a highly functional intermediate C, which has been used in the synthesis of manzacidin B [95]. Among the plethora of olefination reactions, the Wittig [96][97] and Horner

Bidirectional cross metathesis and ring-closing metathesis/ring opening of a C₂-symmetric building block: a strategy for the synthesis of decanolide natural products

• Bernd Schmidt and
• Oliver Kunz

Beilstein J. Org. Chem. 2013, 9, 2544–2555, doi:10.3762/bjoc.9.289

• carboxylic acid and (iii) a Ru–lipase-catalyzed dynamic kinetic resolution to establish the desired configuration at C9. Ring closure was accomplished by macrolactonization. Curvulide A was synthesized from stagonolide E through Sharpless epoxidation. Keywords: dienes; enzyme catalysis; lactones; metathesis

• reported upon incorporation of substituents has been reported in the course of an octalactin synthesis [61]. Having established a reliable route to stagonolide E, we investigated its epoxidation under Sharpless conditions [63]. We expected that this transformation would give either curvulide A [30] or one

• of its diastereomers, and help to resolve the remaining structural ambiguities, i.e. the absolute configurations at C4, C5 and C6. Based on the transition-state model for the Sharpless epoxidation of allylic alcohols bearing a stereogenic centre in the allylic position [64], we expected that

Synthesis of the spiroketal core of integramycin

• Evgeny. V. Prusov

Beilstein J. Org. Chem. 2013, 9, 2446–2450, doi:10.3762/bjoc.9.282

• PMB-protected 3-hydroxypropanal via Horner–Wadsworth-Emmons olefination, reduction to the allylic alcohol and Sharples epoxidation [8] (Scheme 2). Subsequent Cu-catalyzed epoxide-opening using methylmagnesium bromide [9] produced an inseparable mixture of 1,2- and 1,3-diol products, which upon

• epoxidation and Myers alkylation. Although the presented route achieves approximately the same overall yield of target compound as that of Floreancig [2] (11.2 vs 11.5%, respectively), it features utilization of easily scalable transformation and upon further optimization of the spiroketalization step would

• , Microbial drugs). Retrosynthetic analysis of integramycin. Synthesis of the aromatic subunit. Sharpless epoxidation/Myers alkylation approach to the C16–C22 carboxylic acid fragment. Coupling of the fragments and spiroketalization. Supporting Information Supporting Information File 527: Experimental

A protecting group-free synthesis of the Colorado potato beetle pheromone

• Zhongtao Wu,
• Manuel Jäger,
• Jeffrey Buter and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2013, 9, 2374–2377, doi:10.3762/bjoc.9.273

• decemlineata, has been developed based on a Sharpless asymmetric epoxidation in combination with a chemoselective alcohol oxidation using catalytic [(neocuproine)PdOAc]2OTf2. Employing this approach, the pheromone was synthesized in 3 steps, 80% yield and 86% ee from geraniol. Keywords: aggregation pheromone

• the secondary alcohol at C-2. The synthesis by Faraldos runs via epoxidation of fluoronerol, subsequent acetylation of the alcohol and solvolysis. In 2010, Waymouth reported the chemoselective, catalytic oxidation of glycerol to dihydroxyacetone (Scheme 1) using catalytic [(neocuproine)PdOAc]2OTf2 (2

• synthesis of the Colorado potato beetle pheromone (Scheme 2). An additional challenge was the presence of an alkene in the substrate, as the orthogonality of 2-catalyzed alcohol oxidations with alkenes had not been studied. In our approach, Sharpless asymmetric epoxidation of readily available geraniol or

Elucidation of the regio- and chemoselectivity of enzymatic allylic oxidations with Pleurotus sapidus – conversion of selected spirocyclic terpenoids and computational analysis

• Verena Weidmann,
• Mathias Schaffrath,
• Holger Zorn,
• Julia Rehbein and
• Wolfgang Maison

Beilstein J. Org. Chem. 2013, 9, 2233–2241, doi:10.3762/bjoc.9.262

• detected similar oxidation products with PSA and rationalize their formation by an initial epoxidation of the endocyclic double bond to give the allyl epoxide 25, which might then be hydrolyzed to two diastereomeric alcohols 26a and 26b. The latter reaction is known for similar allyl epoxides under

• allylic CH-bonds. For β-ionone, for example, we have previously observed epoxidation to be the major oxidation pathway. It should be noted, that all three compounds 24, 26a and 26b are new derivatives of vitispirane 24 with potentially interesting properties as flavors. The relative stereochemistry of 26a

• vitispirane derivatives 24, 26a and 26b were isolated. In this case, the oxidation pathway is not favoring products of allylic oxidation but most likely those of epoxidation with subsequent hydrolysis of the epoxide. HPLC protocols with chiral stationary phases allow the separation of racemic mixtures of

Synthesis and biological activities of the respiratory chain inhibitor aurachin D and new ring versus chain analogues

• Xu-Wen Li,
• Jennifer Herrmann,
• Yi Zang,
• Philippe Grellier,
• Soizic Prado,
• Rolf Müller and
• Bastien Nay

Beilstein J. Org. Chem. 2013, 9, 1551–1558, doi:10.3762/bjoc.9.176

• naphthalene analogue, yet without totally explaining the observed cytotoxic activity of the compounds. Finally, a synthetic entry is given to the complete carboheterocyclic core of aurachin H through the N-oxidation/epoxidation of aurachin D and a shorter chain analogue, followed by subsequent biomimetic

• the double oxidation of the quinolone nitrogen and the olefin epoxidation (2',3'-position) of the farnesyl chain, with the epoxide being ring-opened with 5-exo selectivity by the 4-hydroxy group of the resulting 4-hydroxyquinoline N-oxide. Taking the geranyl analogue 9 as a model compound (Scheme 2

• spontaneous cyclization of intermediate 21b, which was not isolated. We also performed the same reaction sequence from aurachin D (4), giving the aurachin-H diepoxide with comparable yields [27]. After optimizing the selectivity of the epoxidation, this reaction may furnish a rapid strategy toward aurachin H

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• using a route analogous to one reported by Smith [38]. Allylation of 24 with (+)-B-allyldiisopinocampheylborane generated the alcohol 25 in high yield and enantioselectivity. Directed epoxidation using VO(acac)2 and tert-butyl hydroperoxide was initially performed in order to furnish 27 directly

Efficient continuous-flow synthesis of novel 1,2,3-triazole-substituted β-aminocyclohexanecarboxylic acid derivatives with gram-scale production

• Sándor B. Ötvös,
• Ádám Georgiádes,
• István M. Mándity,
• Lóránd Kiss and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1508–1516, doi:10.3762/bjoc.9.172

• -aminocyclohexanecarboxylates 11–14 were prepared previously by a diastereoselective epoxidation of the corresponding 2-aminocyclohexenecarboxylates, followed by a regioselective oxirane ring opening with NaN3 [68]. Three different alkynes (phenylacetylene, diethyl acetylenedicarboxylate and ethynyl ferrocene) were employed as

Metal-free aerobic oxidations mediated by N-hydroxyphthalimide. A concise review

• Lucio Melone and
• Carlo Punta

Beilstein J. Org. Chem. 2013, 9, 1296–1310, doi:10.3762/bjoc.9.146

• aerobic oxidation of aldehydes could be performed for the in situ generation of the corresponding peracids in the presence of NHPI, promoting co-oxidative processes catalyzed by PINO. In an early protocol, we reported the NHPI-catalyzed selective aerobic epoxidation of α-olefins and cyclic olefins in the

• presence of stoichiometric amounts of aldehydes [52]. The experimental results revealed an opposite selectivity with respect to classical epoxidation by peracids, with internal olefins, which were unreactive under our operating conditions. We suggested a free-radical mechanism according to which the acyl

• aerobic oxidation of cellulose fibers. Molecule-induced homolysis by peracids. Molecule-induced homolysis of NHPI/m- chloroperbenzoic acid system. Proposed mechanism for the NHPI/CH3CHO/O2-mediated epoxidation. NHPI/CH3CHO-mediated aerobic oxidation of alkyl aromatics. Light-induced generation of PINO

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• stereoselective sequence involving a Myers alkylation and a Shi epoxidation. Ring-opening of this epoxide with a vinylcopper complex afforded alcohol 26 instead of the expected product 27. An unusual Lewis acid promoted Payne rearrangement of an α-trityloxy epoxide is proposed to account for this outcome

• . Keywords: Lewis acid; lyconadin A; Myers alkylation; Payne rearrangement; Shi epoxidation; Introduction Lyconadin A (1, Figure 1) was isolated from the club moss Lycopodium complanatum in 2001 by Kobayashi and co-workers [1]. Subsequent to this discovery, lyconadins B–F were isolated and characterized [2

• believed that this compound could be prepared from alkene 6 in two consecutive epoxidation–ring-opening sequences involving vinyl nucleophiles. We anticipated that a chiral catalyst such as one of the ketones developed by Shi and co-workers [15][16][17][18] would control the stereochemistry of the

Efficient regio- and stereoselective access to novel fluorinated β-aminocyclohexanecarboxylates

• Loránd Kiss,
• Melinda Nonn,
• Reijo Sillanpää,
• Santos Fustero and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2013, 9, 1164–1169, doi:10.3762/bjoc.9.130

• –fluorine or oxo–fluorine exchange. Keywords: amino acids; epoxidation; fluorination; hydroxylation; stereoselective reaction; Introduction Fluorine chemistry is an expanding area of research that has generated increasing interest in pharmaceutical and medicinal chemistry in recent years because of its

• follows two different strategies. One is based on regio- and stereoselective hydroxylation via iodooxazine formation, followed by fluorination, while the other includes stereoselective epoxidation and regioselective oxirane opening, followed by hydroxy–fluorine exchange. In the former protocol, amino

• NaOEt in EtOH at 0 °C to furnish all-cis hydroxylated amino ester 5 with the hydroxy group on position 4 of the skeleton (Scheme 1, Figure 2). Hydroxylated amino ester 5 was also prepared via the alternative route involving stereoselective epoxidation. Cyclohexene β-amino ester 1 underwent C–C double

Synthesis of the tetracyclic core of Illicium sesquiterpenes using an organocatalyzed asymmetric Robinson annulation

• Lynnie Trzoss,
• Jing Xu,
• Michelle H. Lacoske and
• Emmanuel A. Theodorakis

Beilstein J. Org. Chem. 2013, 9, 1135–1140, doi:10.3762/bjoc.9.126

• (0)-catalyzed carbomethoxylation [87][88][89][90] produced the desired C-ring lactone 20 in 61% yield. Epoxidation of the C-6/C-7 enone with NaOH/H2O2 followed by oxidative cleavage of the C-11 terminal alkene under OsO4/NaIO4 conditions [91][92] afforded the corresponding C-11 aldehyde. Exposure of

Camera-enabled techniques for organic synthesis

• Steven V. Ley,
• Richard J. Ingham,
• Matthew O’Brien and
• Duncan L. Browne

Beilstein J. Org. Chem. 2013, 9, 1051–1072, doi:10.3762/bjoc.9.118

• of this device was for the preparation of a series of hydrazones. A continuous aqueous extraction to remove the excess hydrazine enabled the product to be collected in high purity (Figure 29). Other applications reported in this work include alkene epoxidation and dithiane preparation. Dispersion of

Study on the total synthesis of velbanamine: Chemoselective dioxygenation of alkenes with PIFA via a stop-and-flow strategy

• Huili Liu,
• Kuan Zheng,
• Xiang Lu,
• Xiaoxia Wang and
• Ran Hong

Beilstein J. Org. Chem. 2013, 9, 983–990, doi:10.3762/bjoc.9.113

• preferentially underwent cyclization to deliver a variety of 3-susbtituted-γ-lactones (25b–d). For comparison, the mCPBA-epoxidation approach in literature always demonstrated that electron-rich alkenes are more reactive leading to the reversal of chemoselectivity [70][71]. A cyclopropane group was also

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• ]. Furthermore, a variety of available reactions to functionalize the double bond, such as reductive (hydrogenation, hydrosilylation, etc.), oxidative (epoxidation, halogenations, dihydroxylation, etc.) or cycloaddition transformations, encourage such vinylation process as an attractive primary tool in organic