A practical synthesis of long-chain iso-fatty acids (iso-C₁₂–C₁₉) and related natural products

• Mark B. Richardson and
• Spencer J. Williams

Beilstein J. Org. Chem. 2013, 9, 1807–1812, doi:10.3762/bjoc.9.210

• commencing with methyl undec-10-enoate (methyl undecylenate) (for iso-C12–C14) or the C15 and C16 lactones pentadecanolide (for iso-C15–C17) and hexadecanolide (for iso-C18–C19). Central to the approaches outlined is the two-step construction of the terminal isopropyl group through addition of

• ], glycosylglycerides [14][15], phosphoglycolipids [16], and various sphingolipids [17][18][19]. The terminal isopropyl group of the iso-fatty acids arises from valine and leucine, which through transamination and decarboxylation reactions yield isobutyryl-CoA and isovaleryl-CoA [20]. These starter units are elongated

• the terminal alkene of methyl undecylenate (available as a pyrolysis product of ricinoleic acid) using isopropyl chloroformate and ethyldichloroaluminium [51], and the synthesis of the iso-C17 acid 6 from methyl ustilate (15,16-dihydroxypalmitate) [52]. Despite the interest in natural products

Synthesis of the reported structure of piperazirum using a nitro-Mannich reaction as the key stereochemical determining step

• James C. Anderson,
• Andreas S. Kalogirou,
• Michael J. Porter and
• Graham J. Tizzard

Beilstein J. Org. Chem. 2013, 9, 1737–1744, doi:10.3762/bjoc.9.200

• , 264.2196; found, 264.2201. (5S*,6R*,Z)-5-Isobutyl-6-isopropyl-4-(4-methoxyphenyl)-3-(2-methylpropylidene)piperazin-2-one (23): To a solution of diamine 21 (61 mg, 0.23 mmol) in THF (5 mL) was added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (EDC, 67 mg, 0.35 mmol) and 1

• %), 343 (12%), 192 (13%); HRMS m/z: calcd for C22H35N2O2, 359.2693; found, 359.2678. (3R*,5S*,6R*)-3,5-diisobutyl-6-isopropyl-4-(4-methoxyphenyl)piperazin-2-one (25): To a solution of piperazinone 23 (170 mg, 0.470 mmol) in MeOH (10 mL) was added palladium on carbon (50 mg, 10% by weight, 0.047 mmol) and

Diastereoselective radical addition to γ-alkyl-α-methylene-γ-butyrolactams and the synthesis of a chiral pyroglutamic acid derivative

• Tomoko Yajima,
• Eriko Yoshida and
• Masako Hamano

Beilstein J. Org. Chem. 2013, 9, 1432–1436, doi:10.3762/bjoc.9.161

• of chiral pyroglutamic acid derivatives using our reaction, starting from a commercially available chiral amino acid. Results and Discussion First, cis-selective isopropyl radical additions to α-methylene-γ-alkyl-γ-lactams were investigated (Table 1). The lactams 1a–1d were synthesized following

• published procedures [10]. The conditions used in our previous study [9] were used as the starting point, and the reactions of 1a–1d (1 equiv) with isopropyl iodide (3 equiv) in CH2Cl2 by using AIBN (0.2 equiv) as a radical initiator and (Me3Si)3SiH (TTMSS) (2 equiv) as a H-donor were performed at room

• temperature under UV irradiation. The reactions of 1a and 1b yielded strong cis-diastereoselectivities, but the reactions of 1c and 1d were less diastereoselective. Next, isopropyl radical additions to N-pivaloyl substrates 3a–3d in the presence of a Lewis acid were investigated (Table 2). The reactions of 3a

True and masked three-coordinate T-shaped platinum(II) intermediates

• Manuel A. Ortuño,
• Salvador Conejero and
• Agustí Lledós

Beilstein J. Org. Chem. 2013, 9, 1352–1382, doi:10.3762/bjoc.9.153

• also prepared quite similar complexes, A5c and A6c, where R labels represent isopropyl groups [40]. Weller and co-workers reported the formation of complex trans-[Pt(Me)(PiPr3)2]+ A7 in which a γ-agostic interaction is located in the fourth coordination site [41]. The addition of tetrahydrofuran (THF

Anionic cascade reactions. One-pot assembly of (Z)-chloro-exo-methylenetetrahydrofurans from β-hydroxyketones

• István E. Markó and
• Florian T. Schevenels

Beilstein J. Org. Chem. 2013, 9, 1319–1325, doi:10.3762/bjoc.9.148

• respectively (Scheme 10). Treatment of the isopropyl derivative 29 under the same acidic conditions provided the triene 54 in 57% yield. Addition of aqueous HCl generated the hemi-ketal 55 in 43% yield. The starting material was recovered in 52% yield. The structures of compounds 53 and 55 were unambiguously

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

• initiators. Azo-initiators were mainly employed for the synthesis of phenol derivatives by aerobic oxidation of isopropyl aromatics. For example, the oxidation of 2,6-diisopropylnaphthalene with air in the presence of α,α’-azobisisobutyronitrile (AIBN) and NHPI, followed by decomposition with sulfuric acid

• system was also applied to the oxygenation of 1,3,5-triisopropylbenzene [17]. However, in this case the conversion of all isopropyl groups was far from being reached, with mono- and di-phenols being the major products, while the yield in benzene-1,3,5-triol was close to 1%. Sheldon and co-workers tested

Cascade radical reaction of substrates with a carbon–carbon triple bond as a radical acceptor

• Hideto Miyabe,
• Ryuta Asada and
• Yoshiji Takemoto

Beilstein J. Org. Chem. 2013, 9, 1148–1155, doi:10.3762/bjoc.9.128

• –allylation of hydroxamate esters 3A–C having an acryloyl moiety (Scheme 1). The reactions were evaluated in CH2Cl2 at −78 °C by employing isopropyl iodide, allyltin reagent, and Et3B as a radical initiator. The enantiomeric purities of products were checked by chiral HPLC analysis. The effect of the

• transfer conditions by using isopropyl iodide and Et3B. The reaction of hydroxamate ester 5 did not give the desired product probably due to polymerization of 5 through the labile acrylamide moiety. In contrast, the reaction of 6A–C proceeded effectively to give the cyclic products 9Aa–9Ca in good yields

• addition to 6A–C was well controlled. The nucleophilic isopropyl radical reacted selectively with the electron-deficient methacryloyl moiety to give the single isomers 9Aa–9Ca. It is also important to note that Z-isomers 9Aa–9Ca were selectively obtained without the formation of corresponding E-isomers

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• intermediate with hydrogen peroxide in tetrahydrofuran [26]. Mixed ethyl/isopropyl trisphosphonate ester 9 has been prepared by treatment of the bisphosphonate 7 with diethyl chlorophosphite and sodium hexamethyldisilazane, and subsequent oxidation of the phosphinate intermediate 8 with iodine in pyridine–THF

Aqueous reductive amination using a dendritic metal catalyst in a dialysis bag

• Jorgen S. Willemsen,
• Jan C. M. van Hest and
• Floris P. J. T. Rutjes

Beilstein J. Org. Chem. 2013, 9, 960–965, doi:10.3762/bjoc.9.110

• ). The first step involved demethylation of 4,4’-dimethoxy-2,2’-bipyridine (1) in 92% yield [31]. Monofunctionalization of the ligand will lead to the highest possible catalyst loading per dendrimer and also prevents cross-linking between dendrimers. Therefore, a 1:1 mixture of isopropyl mesylate (5) and

The conjugation of nonsteroidal anti-inflammatory drugs (NSAID) to small peptides for generating multifunctional supramolecular nanofibers/hydrogels

• Jiayang Li,
• Yi Kuang,
• Junfeng Shi,
• Yuan Gao,
• Jie Zhou and
• Bing Xu

Beilstein J. Org. Chem. 2013, 9, 908–917, doi:10.3762/bjoc.9.104

• hydrogel and exhibits a maximum G' of 7.8 Pa and critical strain 0.57%, clearly indicating that the isopropyl-substituted phenyl group is less efficient at providing aromatic–aromatic interaction for hydrogelation than naproxen or flubiprofen group are. After obtaining the critical strains of the hydrogels

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• bond with the correct stereochemistry and the introduction of the pendant isopropyl group present in the target. The intermediate cyclic carbamate 2 is not isolated but cleaved into aminoalcohol 3 to simplify purification. The conversion of aminoalcohol 3 into (–)-dendrobine (4), hinges on the use of

Synthesis and evaluation of cell-permeable biotinylated PU-H71 derivatives as tumor Hsp90 probes

• Tony Taldone,
• Anna Rodina,
• Erica M. DaGama Gomes,
• Matthew Riolo,
• Hardik J. Patel,
• Raul Alonso-Sabadell,
• Danuta Zatorska,
• Maulik R. Patel,
• Sarah Kishinevsky and
• Gabriela Chiosis

Beilstein J. Org. Chem. 2013, 9, 544–556, doi:10.3762/bjoc.9.60

• biotin directly or via a linker through an amide bond. We chose to make analogues of both 1a and 1b because the isopropyl group in 1a may result in considerable effects on cell-permeability properties due to its increased lipophilicity, while having little effect on the affinity for Hsp90. While it is

• rotamers was present and not a mixture of two compounds. Additionally, intermediate 3 also demonstrates a complex NMR spectrum indicative of the presence of two rotamers. All of this shows that, unlike the proton, the isopropyl group is bulky enough to hinder rotation of the tertiary amides and to enable

• ), despite the fact that both 1a and 1b bound Hsp90 with similar affinity (24.5 versus 26 nM for 1a and 1b, respectively). This is likely a result of increased steric crowding of the bulky isopropyl group in analogues of 1a. Second, in terms of the linkers, the carbon series appeared to have a somewhat

Inter- and intramolecular enantioselective carbolithiation reactions

• Asier Gómez-SanJuan,
• Nuria Sotomayor and
• Esther Lete

Beilstein J. Org. Chem. 2013, 9, 313–322, doi:10.3762/bjoc.9.36

• er (84% yield) was produced (Scheme 14). Substituted alkenes may also be used in these reactions, and 3,3-disubstituted indolines 42 are obtained in moderate to high enantiomeric excesses, depending on the nature of the substituent on the alkene (Scheme 15) [49]. The steric demand of an isopropyl

Synthesis and ring openings of cinnamate-derived N-unfunctionalised aziridines

• Alan Armstrong and
• Alexandra Ferguson

Beilstein J. Org. Chem. 2012, 8, 1747–1752, doi:10.3762/bjoc.8.199

• -aziridines to ring-opening chemistry. To the best of our knowledge, only four papers exist detailing the regioselective ring opening of NH-aziridine-2-carboxylates to provide amino-acid derivatives [16][17][18][19]. The substrate scope has been limited to NH-aziridine-2-carboxylates derived from isopropyl

Polysiloxane ionic liquids as good solvents for β-cyclodextrin-polydimethylsiloxane polyrotaxane structures

• Narcisa Marangoci,
• Rodinel Ardeleanu,
• Laura Ursu,
• Constanta Ibanescu,
• Maricel Danu,
• Mariana Pinteala and
• Bogdan C. Simionescu

Beilstein J. Org. Chem. 2012, 8, 1610–1618, doi:10.3762/bjoc.8.184

• -glycidoxypropyl)polydimethylsiloxane prepolymer with Mn = 1250 until the solution became turbid (after approximately 72 h) at 65 °C, followed by the reaction of epoxide functionalities with 4-aminophenyltriphenylmethane (APhTPhM) (saturated solution in isopropyl alcohol) for 8 h at 65 °C. The slurry was then

Influence of cyclodextrin on the solubility of a classically prepared 2-vinylcyclopropane macromonomer in aqueous solution

• Helmut Ritter,
• Jia Cheng and
• Monir Tabatabai

Beilstein J. Org. Chem. 2012, 8, 1528–1535, doi:10.3762/bjoc.8.173

• . Therefore, we came to the conclusion that the Me2-β-CD ring preferably includes the vinylcyclopropane unit instead of the isopropyl unit. The supramolecular complex 7 shows the typical LCST behavior (31.7 °C) of poly(NiPAAm) (Figure 4). After free radical initiated ring-opening polymerization of 5, a

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• amines Me2N(iPr) (26, MCA = 551.7 kJ/mol), MeN(iPr)2 (39, MCA = 557.3 kJ/mol) and N(iPr)3 (16, MCA = 536.0 kJ/mol) is helpful. In the absence of steric effects a systematic increase in the MCA value is expected on replacing methyl by isopropyl substituents. However, the number of gauche interactions

• cation adduct than in the neutral amine. Figure 2 shows the projection through the C–N bond of one of the isopropyl-groups in 16Me. Trialkyl- and triarylphosphanes are equally potent nucleophiles, whose use in catalytic processes is, however, often limited due to their oxygen sensitivity. Table 2 lists

Chemo-enzymatic modification of poly-N-acetyllactosamine (LacNAc) oligomers and N,N-diacetyllactosamine (LacDiNAc) based on galactose oxidase treatment

• Christiane E. Kupper,
• Ruben R. Rosencrantz,
• Birgit Henßen,
• Helena Pelantová,
• Stephan Thönes,
• Anna Drozdová,
• Vladimir Křen and
• Lothar Elling

Beilstein J. Org. Chem. 2012, 8, 712–725, doi:10.3762/bjoc.8.80

• change of the fermentation temperature to 25 °C was followed by the addition of isopropyl β-D-thiogalactopyranoside (IPTG) yielding a concentration of 1 mM. Additionally a feed (approx. 0.1 mL/min) of 50% (v/v) glycerol in water was applied. Cultivation was terminated 2 h after IPTG addition, yielding 60

Mutational analysis of a phenazine biosynthetic gene cluster in Streptomyces anulatus 9663

• Orwah Saleh,
• Katrin Flinspach,
• Lucia Westrich,
• Andreas Kulik,
• Bertolt Gust,
• Hans-Peter Fiedler and
• Lutz Heide

Beilstein J. Org. Chem. 2012, 8, 501–513, doi:10.3762/bjoc.8.57

• cells harbouring plasmid pHis8-OS03 were cultivated in 2 L of liquid TB medium containing 50 μg·mL−1 kanamycin and grown at 37 °C to an A600 of 0.6. The temperature was lowered to 20 °C, and isopropyl-1-thio-β-D-galactopyranoside was added to a final concentration of 0.5 mM. The cells were cultured for

Self-assembly of Ru₄ and Ru₈ assemblies by coordination using organometallic Ru(II)₂ precursors: Synthesis, characterization and properties

• Sankarasekaran Shanmugaraju,
• Dipak Samanta and
• Partha Sarathi Mukherjee

Beilstein J. Org. Chem. 2012, 8, 313–322, doi:10.3762/bjoc.8.34

• code: Ru = green; O = red; N = blue; C = dark gray. All hydrogen atoms, triflate counter anions, isopropyl and methyl groups of the p-cymene moiety are omitted for the sake of clarity. 1H (left) and 19F (right) NMR spectrum of the macrocycle 2c recorded in CD3CN with the peak assignments. Side (left

• ) and top (right) view of the energy-minimized structures of the octanuclear macrocycle 2c. Color code: green = Ru, blue = N, red = O, gray = C. The hydrogen atoms, methyl and isopropyl group of the cymene moiety have been removed for the sake of clarity. UV–vis absorption spectrum (left) of macrocycles

A general and facile one-pot process of isothiocyanates from amines under aqueous conditions

• Nan Sun,
• Bin Li,
• Jianping Shao,
• Weimin Mo,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2012, 8, 61–70, doi:10.3762/bjoc.8.6

• similar activity as linear alkylamines (Table 2, entries 1–9). The relative low yields of isopropyl isothiocyanate and tert-butyl isothiocyanate were ascribed to their volatility loss associated with isolation (Table 2, entries 1 and 3). The substituent pattern on the phenyl ring of arylamines exhibited

• short silica column using petroleum ether as eluent. Isopropyl isothiocyanate (CAS No: 2253-73-8, Table 2, entry 1): Yield: 85%; colorless oil; IR (neat): 2079 cm−1; 1H NMR (CDCl3) δ 1.37 (d, J = 7.0 Hz, 6H), 3.88–3.95 (m, 1H); GC–EIMS m/z: 101 [M+, 100%]. n-Butyl isothiocyanate (CAS No: 592-82-5, Table

On the control of secondary carbanion structure utilising ligand effects during directed metallation

• Andrew E. H. Wheatley,
• Jonathan Clayden,
• Ian H. Hillier,
• Alison Campbell Smith,
• Mark A. Vincent,
• Laurence J. Taylor and
• Joanna Haywood

Beilstein J. Org. Chem. 2012, 8, 50–60, doi:10.3762/bjoc.8.5

• -position is not blocked (contrast this scenario with the conversion of 4-H into 4-Lil·3THF) recently led us to examine the hitherto unachievable formation of tertiary carbanions by directed lateral lithiation [16][17]. Accordingly, 2-isopropyl-N,N-diisopropylbenzamide (5-H) has been used to source 5-Lil·L

Novel fatty acid methyl esters from the actinomycete Micromonospora aurantiaca

• Jeroen S. Dickschat,
• Hilke Bruns and
• Ramona Riclea

Beilstein J. Org. Chem. 2011, 7, 1697–1712, doi:10.3762/bjoc.7.200

• isopropyl group (m/z = 43 and m/z =143) shifted to m/z = 50 and m/z = 145 in agreement with the deuterium labelling of this portion of the molecule. The labelling was also introduced into the iso-odd FAMEs 102 and 103 (Figures S3C to S3F of Supporting Information File 1) and the higher homologue methyl 15

Asymmetric synthesis of quaternary aryl amino acid derivatives via a three-component aryne coupling reaction

• Elizabeth P. Jones,
• Peter Jones,
• Andrew J. P. White and
• Anthony G. M. Barrett

Beilstein J. Org. Chem. 2011, 7, 1570–1576, doi:10.3762/bjoc.7.185

• 1 the ensuing carbanion 5 was not aryl as expected but instead benzylic, due to an inter- or intramolecular proton transfer. Kinetic protonation of this anion on the face opposite to the isopropyl group accounted for the observed diastereoselectivity of the reaction (Scheme 3). To extend this

• and the dr to 92% and 96:4, respectively (Scheme 5). The major diastereoisomer was confirmed to have the isopropyl and aryl moieties syn, by 1H NMR NOESY analysis; a clear NOESY correlation was observed between the methyl group and the proton at C-3 (Figure 1). The scope of the reaction was then

• exposure to 0.5 M HCl, epimerization of the isopropyl group at C-3 occurs in near quantitative yield, giving adduct 13 (Scheme 10). The electron-withdrawing effect of the carbonyl moiety must increase the acidity of the C-3 proton to such an extent that the acidic media simply epimerizes at this center to

A novel high-yield synthesis of aminoacyl p-nitroanilines and aminoacyl 7-amino-4-methylcoumarins: Important synthons for the synthesis of chromogenic/fluorogenic protease substrates

• Xinghua Wu,
• Yu Chen,
• Herve Aloysius and
• Longqin Hu

Beilstein J. Org. Chem. 2011, 7, 1030–1035, doi:10.3762/bjoc.7.117

• anhydride was converted in situ to the selenocarboxylate by reaction with NaHSe; and 3) the in situ generated selenocarboxylate reacted immediately with the azide. Isopropyl chloroformate was chosen to activate amino acids because the corresponding mixed anhydrides were relatively more resistant to

• that Boc-Arg-OH∙HCl could be activated with isopropyl chloroformate and the activated form was converted smoothly to the corresponding selenocarboxylate followed by the reaction with p-nitrophenyl azide to give the p-nitroanilide 16 in 81% yield (Table 2, entry 2). A dipeptide-pNA, Boc-Ser-Phe-pNA (18

• and spectroscopic data of all amides were consistent with their structures. Synthesis of aminoacyl-pNAs and aminoacyl-AMCs starting from amino acids by activation with isopropyl chloroformate (procedure B). To a solution of Nα-protected amino acid (0.5 mmol) and N-methylpiperidine (61 µL, 0.5 mmol) in