De novo macrolide–glycolipid macrolactone hybrids: Synthesis, structure and antibiotic activity of carbohydrate-fused macrocycles

• Richard T. Desmond,
• Anniefer N. Magpusao,
• Chris Lorenc,
• Jeremy B. Alverson,
• Nigel Priestley and
• Mark W. Peczuh

Beilstein J. Org. Chem. 2014, 10, 2215–2221, doi:10.3762/bjoc.10.229

• part of ester linkages; in 4 they are a carbamate and ether, respectively. Modest antifungal activity against C. neoformans and A. fumigatis were also noted for 4 [13]. Here we report on two new natural product-like 12-membered ring macrolides 5 and 6 (Scheme 1) where the pyranose is fused to the

Building complex carbon skeletons with ethynyl[2.2]paracyclophanes

• Ina Dix,
• Lidija Bondarenko,
• Peter G. Jones,
• Thomas Oeser and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 2013–2020, doi:10.3762/bjoc.10.209

• extensive column chromatography/recrystallization. Isomer 11 is chiral and could be separated on a column impregnated with cellulose tris(3,5-dimethylphenyl)carbamate. The bridge-extended cyclophane precursor 18 furnished the ring-enlarged cyclophanes 19 and 20 on Glaser–Hay coupling. Cross-coupling of 4

• chiral compound, was resolved into its enantiomers on a OD-column impregnated with cellulose tris(3,5-dimethylphenyl) carbamate using hexane/propan-2-ol (9:1) as an eluent and a UV-detector set at 254 nm. A baseline separation was achieved and the two enantiomers had [α]D25 = −44 ° (c 0.375, hexane

Efficient CO₂ capture by tertiary amine-functionalized ionic liquids through Li⁺-stabilized zwitterionic adduct formation

• Zhen-Zhen Yang and
• Liang-Nian He

Beilstein J. Org. Chem. 2014, 10, 1959–1966, doi:10.3762/bjoc.10.204

• liquid absorbents allowing for reversible CO2 chemisorption [31][32][33][34][35]. In general, two absorbent molecules are involved to react with one CO2 molecule generating ammonium carbamate (Scheme 1a) or ammonium alkyl formate (Scheme 1b). Hence, increasing the 1:2 (CO2:absorbent molecule

• formation of ammonium carbamate as shown in Scheme 1a [38]. Notably, the CO2 capacity of guanidine-functionalized ILs increased in the order of [TMGLi][NTf2] (0.65) < [OctTMGLi][NTf2] (0.80) < [PEG150MeTMGLi][NTf2] (0.89 mol CO2 absorbed per mol of base) (Table 1, entries 5–7), indicating that the CO2

• cm−1 after reaction with CO2. A characteristic peak centered at 1685 cm−1 is assigned to the stretching vibration of the carbonyl group in the zwitterionic alkyl carbamate, which is quite different from that in HCO3− (1588 cm−1). For the reaction of [PEG150MeBu2NLi][NTf2] with CO2, a new band at 1635

A promising cellulose-based polyzwitterion with pH-sensitive charges

• Thomas Elschner and
• Thomas Heinze

Beilstein J. Org. Chem. 2014, 10, 1549–1556, doi:10.3762/bjoc.10.159

• of novel polyzwitterions based on cellulose carbamate with carboxylic- and primary amino groups is discussed. Starting from cellulose carbonate, the fully protected zwitterion is efficiently synthesized that could be converted into the polyanion, polycation, and polyzwitterion via the orthogonal

• triethylamine deficiency conditions in order to avoid cross-linking of the polymer chains via carbonate moieties resulting from the strong basicity of the trialkylamine [22]. The aminolysis yields the (3-ethoxy-3-oxopropyl)(N-Boc-2-aminoethyl)cellulose carbamate 4 with a DSβ-alanine ester of 0.88 and a DSBoc

• -EDA of 0.95 that indicates a similar reactivity of the amines applied and the conversion of 95% of the carbonate moieties into the carbamate. Moreover, a random distribution of the substituents within the repeating unit and the polymer backbone can be assumed. From cellulose carbamate 4, the polyanion

Carbohydrate PEGylation, an approach to improve pharmacological potency

• M. Eugenia Giorgi,
• Rosalía Agusti and
• Rosa M. de Lederkremer

Beilstein J. Org. Chem. 2014, 10, 1433–1444, doi:10.3762/bjoc.10.147

• protonable amines into neutral amide or carbamate linkers. Even though PEGylation of chitosan via the amino group is the most commonly used method a number of examples of polysaccharide derivatisation on the hydroxy groups have been reported. Chitosan-O-poly(ethylene glycol) graft copolymers were synthesized

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• TBAB (tetrabutylammonium bromide), TBAI (tetrabutylammonium iodide), TMAC (tetramethylammonium chloride) or 18-crown-6. The best result was obtained with TBAB and 18-crown-6 catalysts in a CH2Cl2/water or AcOEt/water mixture (yields included from 72 to 85%). The carbamate anion is another nucleophilic

Synthesis of fluorescent (benzyloxycarbonylamino)(aryl)methylphosphonates

• Michał Górny vel Górniak,
• Anna Czernicka,
• Piotr Młynarz,
• Waldemar Balcerzak and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 741–745, doi:10.3762/bjoc.10.68

• tribromides gave far less satisfactory results because the obtained crude products were difficult to purify. The obtained phosphites were reacted with benzaldehyde and benzyl carbamate, according to literature [18][19][20], providing the desired diaryl (benzyloxycarbonylamino)(phenyl)methylphosphonates

• restricted rotation around the C–N bound of their carbamate group. As a consequence, they exist in solution in cis- and trans-forms, with the equilibrium strongly shifted towards the formation of trans-isomers [22]. Synthesis of diaryl (benzyloxycarbonylamino)(aryl)methylphosphonates By applying the same

Synthesis of chiral N-phosphinyl α-imino esters and their application in asymmetric synthesis of α-amino esters by reduction

• Yiwen Xiong,
• Haibo Mei,
• Lingmin Wu,
• Jianlin Han,
• Yi Pan and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 653–659, doi:10.3762/bjoc.10.57

• esters [6][7][8][9][10]. Up to now, a series of nucleophilic substrates have been reported to react with α-imino esters, such as enamine [11][12][13][14], carbamate ammonium ylide [15], 1,3-dipolar cycle [16], boronic acid [17], acetylide [18], proparygylic anion [19] and ketene silyl acetal [20]. These

Direct and indirect single electron transfer (SET)-photochemical approaches for the preparation of novel phthalimide and naphthalimide-based lariat-type crown ethers

• Dae Won Cho,
• Patrick S. Mariano and
• Ung Chan Yoon

Beilstein J. Org. Chem. 2014, 10, 514–527, doi:10.3762/bjoc.10.47

• the heteroatom-containing, crown ether ring systems. A notable feature of these reactions is their remarkable chemoselectivity. Alternative pathways initiated by intramolecular SET from the carbamate nitrogen donor sites [57] to the phthalimide acceptor moiety excited state, even though

Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

• Peter H. Huy,
• Julia C. Westphal and
• Ari M. P. Koskinen

Beilstein J. Org. Chem. 2014, 10, 369–383, doi:10.3762/bjoc.10.35

• configurationally labile amino aldehyde intermediates [55][56]. Basically any carbamate or amide protecting group (= PG) orthogonal to the benzyl moiety would be suitable for this strategy. Furthermore, we decided to surrender protection of the OH functions in the synthesis of intermediates D and C in order to

• , phenylalanine, phenylglycine and methionine 1a–d were converted to their N-benzyl-N-carbamate-protected derivatives 2a–d (PG = Cbz, Boc) in a practical one pot procedure through combination of Quitt´s reductive benzylation protocol [61] and a Schotten–Baumann acylation [62][63] in 70–95% yield (Scheme 1). While

• carbamate protected amino acid derivatives 3 (remaining as impurity in the isolated products 2), quantitative benzylation (1→I) was ensured by successive addition of three portions of benzaldehyde/NaBH4 (Quitt´s procedure [61] → two portions) and by maintaining the pH at a value of 10–11. The extractive

Diversity-oriented synthesis of dihydrobenzoxazepinones by coupling the Ugi multicomponent reaction with a Mitsunobu cyclization

• Lisa Moni,
• Luca Banfi,
• Andrea Basso,
• Alice Brambilla and
• Renata Riva

Beilstein J. Org. Chem. 2014, 10, 209–212, doi:10.3762/bjoc.10.16

• easy reaction of this electron-rich benzylamine with CO2 to give an insoluble carbamate. Skipping the extractive purification and directly using the crude amine in the ensuing sequence gave again erratic yields and was troublesome because of the difficult separation of the Ugi adducts 9 from

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

• Curtius rearrangement, upon heating the intermediate isocyanate was trapped with EtOH to yield ethyl carbamate protected amine 141. Deprotection of the Alloc-group [126] and chloro carbamate formation furnished 142. Exposure of this compound to a silver source led to the formation of the five-membered

• (see Scheme 21), followed by the formation of an acid-azide. Shiori version [146][147] of the Curtius rearrangement with concomitant addition of MeOH to the intermediate isocyanate afforded carbamate 171. Oxetane 171 was then opened under Lewis-acidic conditions. The deprotected alcohol was protected

• demercurization [128][129] sequence (through intermediate 177) yielding 178. The oxindole protecting group was then removed, followed by reduction of the carbamate to the remaining missing methyl group [151] to finish gelsemine (146). The total synthesis of the monoterpenoid-indole alkaloid gelsemoxonine (197

Synthesis of novel derivatives of 5-hydroxymethylcytosine and 5-formylcytosine as tools for epigenetics

• Anna Chentsova,
• Era Kapourani and
• Athanassios Giannis

Beilstein J. Org. Chem. 2014, 10, 7–11, doi:10.3762/bjoc.10.2

• the corresponding carbamates 7a–c. The reaction of aldehyde 4 and vinylmagnesium bromide yielded directly carbamate 7d. Surprisingly, the reaction of derivative 5 bearing a N-(TCBoc)2 group with organometallic compounds (methylmagnesium bromide, THF, 0 °C → room temperature, lithium (trimethylsilyl

Oligomeric epoxide–amine adducts based on 2-amino-N-isopropylacetamide and α-amino-ε-caprolactam: Solubility in presence of cyclodextrin and curing properties

• Julian Fischer and
• Helmut Ritter

Beilstein J. Org. Chem. 2013, 9, 2803–2811, doi:10.3762/bjoc.9.315

• pressure and the product dried in vacuo. 11.9 g (62.9 mmol = 87.8%) of a colorless oil was obtained. FTIR (diamond) ν (cm−1): 3500–3200 (br, NH), 1753 (s, ester), 1695 (vs, carbamate); 1H NMR (300 MHz, CDCl3) δ 5.22 (s, 1H, NH), 3.78 (d, J = 5.9 Hz, 2H, CH2), 3.62 (s, 3H, OCH3), 1.33 (s, 9H, RC(CH3)3); 13C

• 102 °C) were obtained. FTIR (diamond) ν (cm−1): 3292, 3222 (br, NH), 1692 (vs, carbamate), 1657, 1548 (vs, amide); 1H NMR (300 MHz, CDCl3) δ 6.41 (s, 1H, RC(O)-NH-R), 5.57 (s, 1H, R-NH-C(O)OR), 3.98 (m, 1H, CH-Me2), 3.66 (d, J = 5.7 Hz, 2H, CH2), 1.36 (s, 9H, RC(CH3)3), 1.06 (d, J = 6.6 Hz, 6H, RHC

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

• density from the reaction center toward nitrogen. In cases where syn-selectivity is observed, the Cram’s chelation control model provides an explanation [56][57]. Chelating metal coordinates between the two carbonyls (the aldehyde and the carbamate), thus forcing the nucleophile to attack from the si-side

• syn-selectivities were achieved with vinylZnCl in Et2O (1:6 anti/syn). Coleman also noticed that the addition of excess ZnCl2 did not increase the syn-selectivity at all. They attributed this to the mono-coordination of the metal to the carbamate instead of the usual “bidentate” chelation control

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• hydroamination of alkenes. Detailed computational studies on the addition of benzyl carbamate to dienes revealed the protodeauration as the rate-determining step of the reaction [34]. Mechanistically, the initial stage was determined dealing with the energetically favourable substitution of the TfO− ligand from

• the gold coordination sphere with the diene (Figure 4). Preferred coordination geometry is the η2-type, with the gold cation coordinating to a single double bond. Either direct coordination of the nucleophile to the gold cation, or reaction of the PH3AuOTf with the carbamate to deliver TfOH and

• [38]. Although prolonged reaction times were required (up to 68 h in refluxing dioxane), remarkable tolerance in terms of carbamate protecting groups (Scheme 7a) and substituents at the carbon chain was recorded (Scheme 7b,c). Soon after the same team disclosed that the titled transformation could be

One-pot sequential synthesis of isocyanates and urea derivatives via a microwave-assisted Staudinger–aza-Wittig reaction

• Diego Carnaroglio,
• Katia Martina,
• Giovanni Palmisano,
• Andrea Penoni,
• Claudia Domini and
• Giancarlo Cravotto

Beilstein J. Org. Chem. 2013, 9, 2378–2386, doi:10.3762/bjoc.9.274

• [1]. Isocyanates play a relevant role as chemical intermediates in the manufacturing of thermoplastic foams, elastomers, adhesives, agrochemicals and pharmaceuticals. The isocyanate group is also widely used as a precursor to several bioactive compounds and drugs that contain urea and carbamate

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

• ) is hydrogenated to the vinylogous carbamate 2.53 in the presence of acetic anhydride. Then the intermediate 2.53 can be subjected to an asymmetric hydrogenation utilising rhodium-based catalyst systems at elevated hydrogen pressures rendering the desired ethyl (R)-nipecotate 2.54 [75]. Uniting the

• scientists and consists of a chiral hydroisoquinoline linked to a (R)-quinuclidinol unit through a carbamate linkage (Figure 6). Upon protonation the tertiary amine of the quinuclidine is expected to resemble the ammonium substructure of muscarine (2.58) [76]. This molecule can be prepared by direct coupling

• of the (R)-quinuclidinol and tetrahydroisoquinoline carbamate partner (Scheme 28). The (R)-quinuclidinol (2.59) itself can be accessed from quinuclidone (2.60), and is most conveniently prepared by alkylation of ethyl isonicotinate (2.61) with ethyl bromoacetate (2.62) followed by full reduction of

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• carbamate formation of the starting material. Upon exposure of 223 to phosphorus pentoxide, the desired isoindolinone 224 was formed in 75% yield. Deprotection led to lactonamycinone (214), which was the substrate for a ytterbium triflate-catalyzed glycosylation to give 215 and 217, respectively

Natural products in synthesis and biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2013, 9, 1897–1898, doi:10.3762/bjoc.9.223

• aminosugar, a hydroxylamine linkage between two sugar subunits, a carbamate, an aromatic iodide, a thioester, and a trisulfide [4]. Natural products have also been used by humankind since ancient times and are part of our traditions and culture, as is evident from the widespread consumption of coffee, tea

A Lewis acid-promoted Pinner reaction

• Dominik Pfaff,
• Gregor Nemecek and
• Joachim Podlech

Beilstein J. Org. Chem. 2013, 9, 1572–1577, doi:10.3762/bjoc.9.179

• were observed, when ester or carbamate groups were present in the substrates (Table 2, entries 8 and 9). The Lewis acid trimethylsilyl triflate possibly cleaves the benzyloxycarbonyl (Z) group, since the similar trimethylsilyl iodide (TMSI) is known to cleave Z protecting groups [17]. Poor yields are

ML212: A small-molecule probe for investigating fluconazole resistance mechanisms in Candida albicans

• Willmen Youngsaye,
• Cathy L. Hartland,
• Barbara J. Morgan,
• Amal Ting,
• Partha P. Nag,
• Benjamin Vincent,
• Carrie A. Mosher,
• Joshua A. Bittker,
• Sivaraman Dandapani,
• Michelle Palmer,
• Luke Whitesell,
• Susan Lindquist,
• Stuart L. Schreiber and
• Benito Munoz

Beilstein J. Org. Chem. 2013, 9, 1501–1507, doi:10.3762/bjoc.9.171

• tert-butyl carbamates 5 prior to undergoing palladium-mediated Suzuki reactions with various boronic acid partners. Under the reaction conditions, the carbamate-protecting group was also cleaved to afford the desired 3-arylindazoles, albeit as the unprotected systems 6. Alkylation with methyl

Formal synthesis of (−)-agelastatin A: an iron(II)-mediated cyclization strategy

• Daisuke Shigeoka,
• Takuma Kamon and
• Takehiko Yoshimitsu

Beilstein J. Org. Chem. 2013, 9, 860–865, doi:10.3762/bjoc.9.99

• -hydroxycarbamate 7 in 67% yield [36]. Thereafter, N-hydroxycarbamate 7 was reacted with TsCl and triethylamine in THF to furnish N-tosyloxycarbamate 8 in 92% yield. With this carbamate 8, we examined the iron(II)-mediated cyclization under various conditions (Table 1). The application of FeBr2 (0.5 equiv)/Bu4NBr

• (1.5 equiv) in EtOH effected cyclization, but the yield of 5a was poor due to the concomitant formation of carbamate 9 (39%) and enone 10 (30%) (Table 1, entry 1). This was in marked contrast to the observation that the same reagent system, i.e., FeBr2 (0.5 equiv)/Bu4NBr (1.2 equiv), allowed the

• provided evidence that these byproducts were generated by the intramolecular cyclization of enone 10 with TMSCl in EtOH, suggesting that the FeCl2/TMSCl system also gave enone 10 in ca. 30% yield [37]. The present study on the aminohalogenation reaction of carbamate 8 has inspired mechanistic insights that

Gold-catalyzed oxycyclization of allenic carbamates: expeditious synthesis of 1,3-oxazin-2-ones

• Benito Alcaide,
• Pedro Almendros,
• M. Teresa Quirós and
• Israel Fernández

Beilstein J. Org. Chem. 2013, 9, 818–826, doi:10.3762/bjoc.9.93

• ][53][54][55], we decided to examine the gold-catalyzed cyclization of N-Boc-allenes with the aim of establishing a protocol for the synthesis of 1,3-oxazin-2-one derivatives in which the carbamate group should serve as the source of CO2. Results and Discussion To explore the effects of various

• by treatment with paraformaldehyde in the presence of diisopropylamine and copper(I) bromide (Crabbé reaction) [59][60]. We employed three different gold salts in our initial screening of catalysts for the model system, allenic carbamate 2a. Initially, the use of AuCl3 and AuCl were tested, but both

• failed to catalyze the reaction. Fortunately, we found that [AuClPPh3]/AgOTf was an excellent catalyst for our purpose. To our delight, the reaction of allenic carbamate 2a at room temperature afforded 3-benzyl-6-methylene-1,3-oxazinan-2-one (3a) bearing an exocyclic double bond as the sole product

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• gives the same good yield added to an attractive (2c + 2c’)/3c ratio of 87/13 (Table 1, entry 3). Formation of the 3-methylindoline 3 is therefore disfavored when a mesyl protecting group is used instead of a carbamate. When this reaction is run with stoichiometric amounts of nickel, the reductive