Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• amino groups of the resin were o-NBS protected by treatment of 4-nitrobenzenesulfonyl chloride (o-NBS-Cl) and sym-collidine in NMP (Scheme 1A, b). Subsequently the resin was N-methylated by Mitsunobu reaction (Scheme 1A, c). Triphenylphosphine (PPh3) was dissolved in dry THF and methanol and shaken with

Strong hyperconjugative interactions limit solvent and substituent influence on conformational equilibrium: the case of cis-2-halocyclohexylamines

• Camila B. Francisco,
• Cleverton S. Fernandes,
• Ulisses Z. de Melo,
• Roberto Rittner,
• Gisele F. Gauze and
• Ernani A. Basso

Beilstein J. Org. Chem. 2019, 15, 818–829, doi:10.3762/bjoc.15.79

• -Fluorocyclohexanol was prepared according the literature [36] to provide cis-2-fluorocyclohexylamine. cis-2-Fluorocyclohexylamine (F) was obtained by a Mitsunobu–Gabriel reaction, as described by Thvedt and co-workers [37]. Under nitrogen atmosphere, trans-2-fluorocyclohexanol (6.00 mmol), triphenylphosphine (6.60

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• propionyl chloride/pyridine, 85%) instead of 9 gave a quantitative yield of the hydroxy ester 12, but a lower dr (4:1). For both cases, we inverted the carbinol centre by Mitsunobu reaction employing p-methoxyphenol. DEAD was used instead of DIAD because of facilitated purification. It was possible to

• . The synthesis of photoreactive tripeptide analogues incorporating photo amino acids 4–6 will be explored thereafter. Actin-binding cyclodepsipeptides, photo amino acids, retrosynthetic cuts of polyketide 7 leading to organozinc compound 8. Synthesis of γ-hydroxy esters 11 and 12, followed by Mitsunobu

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• offset the limitations of a resolution-based protocol, (R)-5 was hydrolyzed with alcoholic KOH to furnish (R)-4 (Scheme 1). Its inversion under the Mitsunobu conditions (Ph3P/DIAD/p-nitrobenzoic acid/THF; KOH/EtOH/25 °C/8 h, 91% over two steps) gave (S)-4 [46]. The benzylation of the hydroxy function in

• of most active HPA-12 isomers, originally proposed (1) and revised (2). Lipase-catalyzed trans-acylation of (±)-4 and subsequent Mitsunobu inversion. Conditions: (i) Zn/THF/allyl bromide/aqueous sat. NH4Cl/25 °C/3 h; (ii) vinyl acetate/lipase (Table 1); (iii) KOH/EtOH/25 °C/6 h; (iv) Ph3P/DIAD/p

Synthesis and fluorescent properties of N(9)-alkylated 2-amino-6-triazolylpurines and 7-deazapurines

• Andrejs Šišuļins,
• Jonas Bucevičius,
• Yu-Ting Tseng,
• Irina Novosjolova,
• Kaspars Traskovskis,
• Ērika Bizdēna,
• Huan-Tsung Chang,
• Sigitas Tumkevičius and
• Māris Turks

Beilstein J. Org. Chem. 2019, 15, 474–489, doi:10.3762/bjoc.15.41

• available 2,6-dichloropurine (1a) by subsequent alkylation of the N(9) position and azido group introduction in C(2) and C(6) positions. The N(9) position of purine was alkylated in two different ways: 1) using alkyl halides in the presence of a strong base, and 2) using alcohols under Mitsunobu conditions

• times. For example, in the case of 1-bromododecane, the reaction required 72 hours to complete. On the other hand, Mitsunobu reaction (method B, Scheme 1) was performed between the corresponding alcohol and 2,6-dichloropurine in anhydrous THF at 0–20 °C for 1–1.5 h, resulting in average yields of 66

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• -hydroxyglutamate [(2S,4R)-81] (Scheme 20) [82]. To synthesize (2S,4S)-81 the inversion of configuration at C4 executed by Mitsunobu reaction preceded oxidation at C5 and the ring opening [82]. O-Benzyl ethers of (2S,4R)-3 and (2S,4S)-3 were prepared by the same methodology [50]. Another approach to the

• intramolecular lactonization to form 83 by implementation of the Mitsunobu reaction. After opening of the lactone ring with trichloroethanol and silylation of the hydroxy group oxidation at C5 was performed in the usual way to give a pyroglutamate 84. Benzyl or p-methoxybenzyl esters 85a or 85b were next

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

• Pierre-Antoine Nocquet,
• Aurélie Macé,
• Frédéric Legros,
• Jacques Lebreton,
• Gilles Dujardin,
• Sylvain Collet,
• Arnaud Martel,
• Bertrand Carboni and
• François Carreaux

Beilstein J. Org. Chem. 2018, 14, 2949–2955, doi:10.3762/bjoc.14.274

• configuration of the stereogenic center bearing the hydroxy group (Scheme 5). With this in mind, the secondary alcohol 23 was engaged in a Mitsunobu reaction using p-nitrobenzoic acid as nucleophile to afford the expected compound 25. Hydrolysis of the ester was achieved using potassium carbonate in methanol to

Synthesis of pyrrolidine-based hamamelitannin analogues as quorum sensing inhibitors in Staphylococcus aureus

• Jakob Bouton,
• Kristof Van Hecke,
• Reuven Rasooly and
• Serge Van Calenbergh

Beilstein J. Org. Chem. 2018, 14, 2822–2828, doi:10.3762/bjoc.14.260

• functionalized side chains are introduced prior to coupling and ring closure to afford 8. This new synthetic route would be more convergent and efficient for the preparation of 3. Retrosynthetic analysis led to 9 and 10 as two key synthons, which would be assembled via a Mitsunobu–Fukuyama reaction, and

• nucleophile [22][23]. Attempts to substitute the alcohol functionality of 12 via displacement of the derived mesylate with NaN3 failed, similar to previously reported difficulties by Trost et al. [24]. The benzamide substituent was therefore introduced via Mitsunobu reaction with N-Boc-protected ortho

• -propanediol (16), which was selectively monoprotected in high yield as TBS ether (Scheme 3) [25]. The remaining alcohol was then substituted for a phthalimide via Mitsunobu reaction. Phthalimide deprotection, acylation with benzoic acid, and removal of the silyl protecting group furnished 10. Fragments 9 and

Synthesis of 1,4-imino-L-lyxitols modified at C-5 and their evaluation as inhibitors of GH38 α-mannosidases

• Maroš Bella,
• Sergej Šesták,
• Ján Moncoľ,
• Miroslav Koóš and
• Monika Poláková

Beilstein J. Org. Chem. 2018, 14, 2156–2162, doi:10.3762/bjoc.14.189

• ). In order to obtain final compounds 5, a configurational inversion of the stereocenter at C-5 in 18 was necessary. The inversion of the configuration was first attempted by a modified Mitsunobu reaction or activation of the hydroxy group by mesylation according to Trajkovic et al. [34]. However, these

Anomeric modification of carbohydrates using the Mitsunobu reaction

• Julia Hain,
• Patrick Rollin,
• Werner Klaffke and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2018, 14, 1619–1636, doi:10.3762/bjoc.14.138

• 238 417281 Haus der Technik e.V., Hollestr. 1, 45127 Essen, Germany, Fax: +49 201 1803269 10.3762/bjoc.14.138 Abstract The Mitsunobu reaction basically consists in the conversion of an alcohol into an ester under inversion of configuration, employing a carboxylic acid and a pair of two auxiliary

• glycosciences. Therefore, this review focuses on the use of the Mitsunobu reaction for modifications of sugar hemiacetals. Strikingly, unprotected sugars can often be converted regioselectively at the anomeric center, whereas in other cases, the other hydroxy groups in reducing sugars have to be protected to

• achieve good results in the Mitsunobu procedure. We have reviewed on the one hand the literature on anomeric esterification, including glycosyl phosphates, and on the other hand glycoside synthesis, including S- and N-glycosides. The mechanistic details of the Mitsunobu reaction are discussed as well as

Recent applications of chiral calixarenes in asymmetric catalysis

• Mustafa Durmaz,
• Erkan Halay and
• Selahattin Bozkurt

Beilstein J. Org. Chem. 2018, 14, 1389–1412, doi:10.3762/bjoc.14.117

• calixarenes and their catalytic performances in the asymmetric Suzuki–Miyaura coupling and Tsuji–Trost allylic alkylation reactions (Scheme 7) [42]. Calix[4]arene mono and dithiophosphines 24–26 were efficiently synthesized from p-tert-butylcalix[4]arene by a one pot Mitsunobu alkylation using

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• alternative way to the desired amine 12a, based on the SN2 reaction of the activated alcohol 13 [34][35] with benzylamine, also failed (Scheme 2). The Mitsunobu approach to convert the hydroxy group into an amine function was also unsuccessful. Although 13 reacted with phthalimide gave the desired product 13a

• of alcohol 13 (derived from D-glucose) with a rigid fragment and we decided to introduce the phenyl ring. Treatment of alcohol 13 with para-nitrophenol under Mitsunobu conditions afforded the nitro compound 14 in 63% yield. Stereoisomeric alditol 15, obtained from D-mannose, was converted analogously

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• . The reaction of 5-amino-4-cyanopyrazole (208) and formamide was carried out by Todorovic et al. [136] under microwave irradiation at 200 °C to give 4-aminopyrazolo[3,4-d]pyrimidine (223) which on iodination with N-iodosuccinimide followed by N1-alkylation (Mitsunobu or substitution) provided

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• -fluoro-2-phosphonoacetate (1) was converted into the α-fluoro-α,β-unsaturated carbonyl 3 using the HWE olefination. The (Z)-isomer was obtained with complete selectivity. Then, reduction of the ester into the corresponding alcohol followed by a Mitsunobu reaction allowed the insertion of the NH

• . This was then converted into a protected amino group employing a Mitsunobu reaction. Finally, removal of the nosyl group, followed by hydrolysis using lithium hydroxide, afforded the targeted isostere 24. Sano and co-workers also worked on the Mg(II)-promoted stereoselective synthesis of (Z

• methyl ester using trimethylsilyldiazomethane, followed by its reduction to the corresponding alcohol and a Mitsunobu reaction, permitted the incorporation of the N-terminal moiety. Then, removal of the Ns group of 28 and deprotection of the primary alcohol was performed to obtain 29 which underwent a

Homologated amino acids with three vicinal fluorines positioned along the backbone: development of a stereoselective synthesis

• Raju Cheerlavancha,
• Ahmed Ahmed,
• Yun Cheuk Leung,
• Aggie Lawer,
• Qing-Quan Liu,
• Marina Cagnes,
• Hee-Chan Jang,
• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2017, 13, 2316–2325, doi:10.3762/bjoc.13.228

• modify the synthesis shown in Scheme 4 to produce the all-syn trifluoroalkane 40b. Thus, the alcohol 37 underwent a Mitsunobu-type inversion of configuration, and O’Hagan’s series of three consecutive fluorination reactions [34] were subsequently applied to successfully deliver the all-syn

Synthesis of benzannelated sultams by intramolecular Pd-catalyzed arylation of tertiary sulfonamides

• Valentin A. Rassadin,
• Mirko Scholz,
• Anastasiia A. Klochkova,
• Armin de Meijere and
• Victor V. Sokolov

Beilstein J. Org. Chem. 2017, 13, 1932–1939, doi:10.3762/bjoc.13.187

• precursor 20 was prepared in one step from the respective sulfonamide 19 and 2-iodobenzyl alcohol employing a Mitsunobu protocol (Scheme 6) [49]. Treatment of 20 with palladium acetate, Ph3P, and sodium hydride in dioxane at 90 °С for 20 h furnished the target sultam 21 in 49% yield. Apparently, the

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

New electroactive asymmetrical chalcones and therefrom derived 2-amino- / 2-(1H-pyrrol-1-yl)pyrimidines, containing an N-[ω-(4-methoxyphenoxy)alkyl]carbazole fragment: synthesis, optical and electrochemical properties

• Daria G. Selivanova,
• Alexei A. Gorbunov,
• Olga A. Mayorova,
• Alexander N. Vasyanin,
• Igor V. Lunegov,
• Elena V. Shklyaeva and
• Georgii G. Abashev

Beilstein J. Org. Chem. 2017, 13, 1583–1595, doi:10.3762/bjoc.13.158

• -disubstituted 2-(pyrrol-1-yl)pyrimidine via Clausson–Kaas condensation (8). Alkylation of 4-methoxyphenol was realized with the help of the traditional base-catalyzed O-alkylation process in acetone media [11]. N-Alkylated carbazole derivatives can be obtained by different methods such as Mitsunobu reaction [12

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• using Mitsunobu reagents Over the last 50 years the Mitsunobu reaction [102] has developed into one of the mainstays in the organic chemist’s toolbox. It has such far reaching potential that it or partial variants of the procedure can now be utilized in glycosylation reactions of unprotected and

• ]. 5.1.2 Esterification of benzoic acids with glycosyl donors: Again in 2015 Kawabata and co-workers applied the Mitsunobu reaction to an unprotected and unactivated donor in the first step of the total synthesis of two ellagitannins. Using a moderate excess

DMAP-assisted sulfonylation as an efficient step for the methylation of primary amine motifs on solid support

• Johnny N. Naoum,
• Koushik Chandra,
• Dorit Shemesh,
• R. Benny Gerber,
• Chaim Gilon and
• Mattan Hurevich

Beilstein J. Org. Chem. 2017, 13, 806–816, doi:10.3762/bjoc.13.81

• of over-methylated amines. The Mitsunobu–Fukuyama reaction was used for the conversion of primary amines to secondary mono-methylated amines in solution using an alcohol and via temporary protection of the amino group to avoid over methylation [17][18][19][20][21]. This method relies on the

• introduction of the o- or p-nitrobenzenesulfonyl groups to primary amines in the first step. The semi-protected sulfonamides can then undergo a selective mono-methylation via Mitsunobu reaction or by direct methylation. The reaction is completed by the selective removal of the sulfonamide group. Miller and

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• the possibility of obtaining 2 via intramolecular epoxide ring-opening of 7 (Scheme 1, method 2). Consequently, an alternative pathway involving the Mitsunobu inversion of 9 (obtained by intramolecular epoxide ring-opening of 8 which is the enantiomer of 6) has been followed to obtain 2 (Scheme 1

• , respectively, in 93% yield. It is to be mention that the NMR spectra and specific rotations of 2 and 29 matched with those reported in the literature [11][14][15]. For the synthesis of compound 3, stereoisomer 29 was subjected to classical two-step Mitsunobu inversion protocol which was successful but poor

• -hydroxy-α-tosyloxy esters 24 and 25. Speculation of simultaneous epoxidation/epoxide-ring opening. Synthesis of chroman diols 2 and 29, respectively. Conversion of 32 into 3 via Mitsunobu inversion. Synthesis of chroman epoxide 5. Supporting Information Supporting Information File 228: Experimental

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• carbocyclic nucleoside methylphosphonate analogues bearing purine bases (adenine and guanine) was accomplished using bio-sourced furfuryl alcohol derivatives. All compounds were prepared using a Mitsunobu coupling between the heterocyclic base and an appropriate carbocyclic precursor. After deprotection, the

• -hydroxycyclopentyl acetate (5) and (+/−)-1-((dimethoxyphosphoryl)methyl)-4-hydroxycyclopent-2-en-1-yl acetate (7). The protection of the tertiary hydroxy groups was necessary in order to avoid competing side reactions during the coupling reaction under Mitsunobu conditions [10]. Compounds (+/−)-5 and (+/−)-7 were

• used as suitable precursors for the synthesis of the target carbocyclic methylphosphonates. Synthesis of cyclopentyl carbocyclic methylphosphonates (+/−)-12 and (+/−)-13 The synthesis of the target compounds was accomplished using a Mitsunobu reaction (Scheme 2) [11]. The coupling of (+/−)-5 with bis

Synthesis of polyhydroxylated decalins via two consecutive one-pot reactions: 1,4-addition/aldol reaction followed by RCM/syn-dihydroxylation

• Michał Malik and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2016, 12, 2602–2608, doi:10.3762/bjoc.12.255

• most likely unstable, we decided to deprotect 20 directly before the planned one-pot procedure and use it without purification. In order to obtain (R)-10, we decided to inverse the configuration at the free hydroxy group in allylic alcohol 19 by Mitsunobu reaction. Despite the fact that the use of

• allylic alcohols as substrates in Mitsunobu reactions can be a challenging task, some successful examples can be found in the literature [49][50]. However, the reaction with benzoic acid did not proceed at all, whereas application of p-nitrobenzoic acid yielded a complicated mixture of products. Therefore

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• protecting group manipulation and installation of the guanidine using S-methylisothiourea 33 (Scheme 5). Mitsunobu cyclisation followed by deprotection and oxidation afforded the azido acids 38 and 39 in 40% yield over 8 steps from amino azides 36 and 37. Synthesis of β-hydroxyenduracididine by Nieuwenhze et

• the guanidine group using isothiourea 33 before cyclisation was effected using Mitsunobu conditions. After a six-step conversion of alkene 44 to nosyl intermediate 42, the synthesis diverged to access both C-2 diastereomers. Displacement of nosylate 42 with sodium azide followed by reduction and amine

A new and expeditious synthesis of all enantiomerically pure stereoisomers of rosaprostol, an antiulcer drug

• Wiesława Perlikowska,
• Remigiusz Żurawiński and
• Marian Mikołajczyk

Beilstein J. Org. Chem. 2016, 12, 2234–2239, doi:10.3762/bjoc.12.215

• to 64%. The remaining two stereoisomers, (−)-1b and (+)-1d, were obtained from (−)-1a and (+)-1c in 71 and 68% yield, respectively, by a two-reaction sequence, in which a Mitsunobu inversion of configuration at C-5 was the key step. Keywords: antiulcer drug; chiral resolution; rosaprostol

• yield of the synthesis of (−)-1a from (+)-3 involving this alternative procedure was increased to 64%. With the two rosaprostol stereoisomers 1a and 1c in hand, the synthesis of the remaining two stereoisomers 1b and 1d was readily accomplished with a Mitsunobu reaction [28] inverting the configuration

• at C-5. In fact, 1a and 1c were obtained through a two-step sequence starting with the methylation of (−)-1a and (+)-1c followed by a one-pot Mitsunobu esterification–hydrolysis as shown in Scheme 6. In detail, treatment of rosaprostols (−)-1a and (+)-1c with diazomethane gave the corresponding