Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• . synthesised the hydroxyleucine moiety found in naturally occurring muraymycins of classes A to C (Scheme 8) [107]. Adapting a strategy developed by Zhu et al., D-serine (59) was stereoselectively converted into the protected amino alcohol 60 [108]. Key intermediate 60 was then Cbz- and acetonide protected to

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• catalyst, in its Z form, which is stabilized due to an intramolecular hydrogen bond (Scheme 14). In 2012, Dong and co-workers studied the catalytic activity of several β-amino alcohol-based squaramide organocatalysts involved in the Michael addition of acetylacetone (36a) to β-nitrostyrene (3a) in

Copper-catalyzed intermolecular oxyamination of olefins using carboxylic acids and O-benzoylhydroxylamines

• Brett N. Hemric and
• Qiu Wang

Beilstein J. Org. Chem. 2016, 12, 22–28, doi:10.3762/bjoc.12.4

• efficiencies were observed in the reactions with more acidic benzoic acids, indicating a correlation of their reactivity to their acidity which remains to be further clarified [44]. Furthermore, when trifluoroacetic acid was employed as an oxygen source, the free 1,2-amino alcohol 4g was isolated, possibly due

Cross metathesis of unsaturated epoxides for the synthesis of polyfunctional building blocks

• Meriem K. Abderrezak,
• Kristýna Šichová,
• Nancy Dominguez-Boblett,
• Antoine Dupé,
• Zahia Kabouche,
• Christian Bruneau and
• Cédric Fischmeister

Beilstein J. Org. Chem. 2015, 11, 1876–1880, doi:10.3762/bjoc.11.201

• cross metathesis of 1 with methyl acrylate was transformed by means of nucleophilic ring-opening of the epoxide to furnish a diol, an alkoxy alcohol and an amino alcohol in high yields. Keywords: cross metathesis; epoxide; ruthenium catalysts; tandem reactions; Introduction Catalytic carbon–carbon

• post-transformation of 4 by ring-opening of the epoxide moiety. The diol 6, methoxy alcohol 7 and amino alcohol 8 were thus prepared by reacting 4 with water, sodium methoxide and aniline, respectively (Scheme 4). The synthesis of 6 proceeded cleanly and did not require any purification procedure (see

• Supporting Information File 1). Similarly, the synthesis of 7 proceeded cleanly and delivered a single regioisomer 7 in quantitative yield. Finally, the amino alcohol 8 was also obtained as a single regioisomer in 61% yield (Scheme 4). Conclusion We have shown through selected examples that cross metathesis

Synthesis of novel N-cyclopentenyl-lactams using the Aubé reaction

• Madhuri V. Shinde,
• Rohini S. Ople,
• Ekta Sangtani,
• Rajesh Gonnade and
• D. Srinivasa Reddy

Beilstein J. Org. Chem. 2015, 11, 1060–1067, doi:10.3762/bjoc.11.119

• . To begin with, the azido alcohol 3 required for the present work was envisaged from Vince lactam (±)-1. The known amino alcohol [31] (prepared from Vince lactam by following literature procedures) was treated with triflyl azide or imidazole sulfonyl azide [32][33] using standard conditions to furnish

Radical-mediated dehydrative preparation of cyclic imides using (NH₄)₂S₂O₈–DMSO: application to the synthesis of vernakalant

• Dnyaneshwar N. Garad,
• Subhash D. Tanpure and
• Santosh B. Mhaske

Beilstein J. Org. Chem. 2015, 11, 1008–1016, doi:10.3762/bjoc.11.113

• plan was to devise a concise and practical synthetic route. The planned synthetic strategy is illustrated in Scheme 2. The synthesis began from Boc-protected trans-amino alcohol 6 [65]. The two-step sequence – tosylation of the secondary alcohol 6 followed by elimination to form the Boc- protected

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• acids emerged next. During the late 1940s, Bretschneider examined the acylation of amino alcohol compounds such as synephrine in much detail (detailed in the later section on amino alcohols). As part of these investigations, and aware of the work Sakami and Toennies [9], he developed acidic O-acylation

• some of these disclosures will be postponed to a later section, where they will be combined with others into an overall evaluation of the use of acidic conditions for chemoselective O-acylation of amino alcohol structural motifs. Besides CF3CO2H and MeSO3H media, acidic O-acylation of hydroxyamino

• and O-phenylacetyl derivatives of DL-serine and threo-DL-phenylserine, as reported in 2003 (using the acyl chlorides in CF3CO2H), derivatives that displayed fungicidal activity [40]. However, by and large, the synthesis of amino acid or amino alcohol derivatives has relied on traditional protective

Chiral phosphines in nucleophilic organocatalysis

• Yumei Xiao,
• Zhanhu Sun,
• Hongchao Guo and
• Ohyun Kwon

Beilstein J. Org. Chem. 2014, 10, 2089–2121, doi:10.3762/bjoc.10.218

• part of the allenoate’s carbonyl group. With the idea of using a natural amino acid as the hydrogen bonding framework, Zhao and co-workers designed the simpler multifunctional chiral N-acyl aminophosphine H5, which they readily synthesized in four steps from a commercially available Boc-protected amino

• alcohol [53]. With 10 mol % of catalyst H5, various arylidenemalononitriles reacted with an allenoate in toluene at room temperature for 1 h to provide various chiral cyclopentenes in 79–99% yield and 80–99% ee (Scheme 22). In particular, the annulations of 2-cyano-3-arylacrylates, with two different

Synthesis of a bifunctional cytidine derivative and its conjugation to RNA for in vitro selection of a cytidine deaminase ribozyme

• Nico Rublack and
• Sabine Müller

Beilstein J. Org. Chem. 2014, 10, 1906–1913, doi:10.3762/bjoc.10.198

• of the phosphoramidite 2 from amino alcohol 13, and subsequent coupling to the 5'-O-deprotected nucleoside 12. I: 1.2 equiv di-tert-butyl dicarbonate, EtOAc, 60 °C, 1.5 h, 98%; II: 5.3 equiv DIPEA, 1.3 equiv (2-cyanoethyl-N,N-diisopropyl)chlorophosphoramidite, DCM, rt, 1.5 h; III: 0.9 equiv 12, 4.5

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• , which was then converted into bromide 75. Debromination and cleavage of the TBDPS protecting group gave protected amino-alcohol 76. Finally, Jones oxidation and removal of the N-Boc protecting group produced crystalline (E)-polyoximic acid (E-9), whose structure was unambiguously confirmed by X-ray

Synthesis of 1-[bis(trifluoromethyl)phosphine]-1’-oxazolinylferrocene ligands and their application in regio- and enantioselective Pd-catalyzed allylic alkylation of monosubstituted allyl substrates

• Zeng-Wei Lai,
• Rong-Fei Yang,
• Ke-Yin Ye,
• Hongbin Sun and
• Shu-Li You

Beilstein J. Org. Chem. 2014, 10, 1261–1266, doi:10.3762/bjoc.10.126

• ) n-BuLi, CO2, THF, −20 °C. (c) (i) (COCl)2, DCM, rt; then TEA, amino alcohol, DCM, rt; (ii) Ph3P, CCl4, TEA, CH3CN, rt. (d) (i) n-BuLi, TMEDA, P(OPh)3, Et2O, −78 °C; (ii) TMSCF3, CsF, Et2O, rt. Comparison of the effect of ligands in the reaction. Evaluation of the ligands and optimization of the

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

• [32], we have employed their 7-step synthesis of a stereoisomerically pure amino alcohol as the key intermediate. According to the previously reported protocol, D-serine (2) was transformed into protected derivative 3 (4 steps, 59% overall yield, Scheme 1). Alcohol 3 was then oxidized to a D-serinal

• sequence. Finally, the previously reported hydrogenolytic debenzylation of 4 [32] provided amino alcohol key intermediate 5 in quantitative yield for the deprotection step and in 29% overall yield over 7 steps from D-serine (2, Scheme 1). It should be noted that Garner's aldehyde is often used instead of

• discouraging its use for the preparation of anti-configured (2S,3S)-3-hydroxyleucine. Zhu and co-workers had based their stereochemical assignment of 5 on the 1H NMR coupling constants of a cyclic derivative of this amino alcohol. We were able to confirm the postulated stereochemical outcome of the Grignard

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

• active natural products [1][2][3][4][5][6][7][8][9], chiral auxiliaries [10][11] and catalysts for asymmetric synthesis [12][13][14]. Especially the 2-substituted 3-hydroxypiperidine scaffold of the general structure B (as one type of an 1,2-amino alcohol) can be found in numerous natural products and

• common precursor ketone D (derived from commercial available amino acids) should deliver the syn-amino alcohol C proceeding though a Felkin–Anh transition state [52][53] (due to the sterically demanding –NBnPG function). Further PG cleavage and cyclodehydration would give rise to cis-B. On the other hand

• , initial deprotection of D (to liberate the Lewis-basic –NHBn moiety) and subsequent reduction passing through a Cram-chelate transition state [54] should deliver the anti-amino alcohol C. After subsequent cyclisation trans-B would result. Noteworthy, this strategy would completely circumvent

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

• attention as a chiral intermediate for the synthesis of numerous amino alcohol derivatives. This review presents some of the most successful carbon chain elongation reactions, namely carbonyl alkylations and olefinations. The literature is reviewed with particular attention on understanding how to avoid the

Stereodivergent synthesis of jaspine B and its isomers using a carbohydrate-derived alkoxyallene as C₃-building block

• Volker M. Schmiedel,
• Stefano Stefani and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2013, 9, 2564–2569, doi:10.3762/bjoc.9.291

• a 1,2-amino alcohol moiety at C-3 and C-4. Due to its interesting structure and biological activities, for instance cytotoxicity and apoptosis promotion of several cancer cell lines [3][4][5][6] the synthesis of this natural product attracted the attention of many research groups resulting in more

• of both diastereomers. The cis-configured amino alcohol moiety at C-3 and C-4 is installed by azidation and subsequent reduction steps leading to the final products. The presented strategy allows the preparation of jaspine B, its enantiomer and two diastereomers, all of which are known for their

A one-pot synthesis of 3-trifluoromethyl-2-isoxazolines from trifluoromethyl aldoxime

• Raoni S. B. Gonçalves,
• Michael Dos Santos,
• Guillaume Bernadat,
• Danièle Bonnet-Delpon and
• Benoit Crousse

Beilstein J. Org. Chem. 2013, 9, 2387–2394, doi:10.3762/bjoc.9.275

• yield the corresponding trifluoromethylated γ-amino alcohols. Keywords: aldoxime; amino alcohol; fluorine; isoxazole; isoxazoline; organo-fluorine; Introduction 2-Isoxazolines are five-membered heterocyclic compounds that have been widely applied in medicinal and organic chemistry. This nucleus is

• different fluorinated building blocks was demonstrated by the easy ring opening of these intermediates with NaBH4 and NiCl2, yielding the corresponding trifluoromethylated γ-amino alcohol. Example of bioactive molecules bearing the 2-isoxazoline nucleus. Dimerization and isomerization products from nitrile

A versatile and efficient approach for the synthesis of chiral 1,3-nitroamines and 1,3-diamines via conjugate addition to new (S,E)-γ-aminated nitroalkenes derived from L-α-amino acids

• Vera Lúcia Patrocinio Pereira,
• André Luiz da Silva Moura,
• Daniel Pais Pires Vieira,
• Leandro Lara de Carvalho,
• Eliz Regina Bueno Torres and
• Jeronimo da Silva Costa

Beilstein J. Org. Chem. 2013, 9, 832–837, doi:10.3762/bjoc.9.95

• the other hand, the azide anion reacted with 2a, in acetonitrile, via a [3 + 2]-cycloaddition in which HNO2 was lost, providing the corresponding 1,2,3-triazole derivative. Direct reduction of 1,3-nitroamine derivatives 9a,b produced the corresponding 1,3-diamines in good yields. Keywords: amino

• alcohol; amino aldehyde; azide addition; Baylis–Hillman reaction; cyanide addition; Michael addition; Introduction Nitroalkenes constitute a class of organic compounds that present exceptional versatility in organic synthesis [1][2][3][4]. They are reactive in Michael reactions with a wide variety of

Synthesis of skeletally diverse alkaloid-like molecules: exploitation of metathesis substrates assembled from triplets of building blocks

• Sushil K. Maurya,
• Mark Dow,
• Stuart Warriner and
• Adam Nelson

Beilstein J. Org. Chem. 2013, 9, 775–785, doi:10.3762/bjoc.9.88

• diastereoiomers; following column chromatography, the major diastereomer 22 was obtained in 70% yield, and was converted into the corresponding amino alcohol 23. The configuration of the amino alcohol 23 was determined by conversion into the corresponding benzamide and comparison with racemic and enantiomerically

• enriched samples (prepared from the commercially available amino acid). Analysis by chiral HPLC indicated that the amino alcohol 23 had (R)-configuration. It was concluded that the sense of diastereoselectivity in the addition 21 → 22 contrasted with that reported by Ellman [21]. However, the sense of

• diastereoselectivity was the same as that reported for the addition of allylmagnesium bromide in dichloromethane to a similar sulfinimine [22]. The amino alcohol 23 was converted into the corresponding o-nitrophenylsulfonamide 24 and, hence, the fluorous-tagged building block 7. The propagating building blocks 8–11

Asymmetric synthesis of a highly functionalized bicyclo[3.2.2]nonene derivative

• Toshiki Tabuchi,
• Daisuke Urabe and
• Masayuki Inoue

Beilstein J. Org. Chem. 2013, 9, 655–663, doi:10.3762/bjoc.9.74

• mixture was filtered through a pad of Celite with THF (30 mL), and the filtrate was concentrated to afford amino alcohol 25, which was used in the next reaction without further purification. A solution of NaNO2 (141 mg, 2.04 mmol) in H2O (1.3 mL) was added to a solution of the above crude amino alcohol 25

Asymmetric desymmetrization of meso-diols by C₂-symmetric chiral 4-pyrrolidinopyridines

• Hartmut Schedel,
• Keizo Kan,
• Yoshihiro Ueda,
• Kenji Mishiro,
• Keisuke Yoshida,
• Takumi Furuta and
• Takeo Kawabata

Beilstein J. Org. Chem. 2012, 8, 1778–1787, doi:10.3762/bjoc.8.203

• racemic diols (s: up to 12) [8] and amino alcohol derivatives (s: up to 54) [9]. Catalyst 2, readily prepared from L-proline, could be employed for the kinetic resolution of amino alcohol derivatives (s: up to 11) [10]. Chiral PPY catalysts with dual functional side chains at C(2) and C(4) of the

Enantioselective total synthesis of (R)-(−)-complanine

• Krystal A. D. Kamanos and
• Jonathan M. Withey

Beilstein J. Org. Chem. 2012, 8, 1695–1699, doi:10.3762/bjoc.8.192

• , and the biological activity of complanine may be understood in terms of controlling these cascades. From a structural perspective, complanine contains a novel trimethylammonium cationic group and can be characterized as possessing a homoconjugated all-Z-diene moiety and an amino alcohol N-acylated

• functionalities. Synthetic studies, also conducted by Nakamura and Uemura, established the absolute structure and configuration as (R)-(−)-complanine (Figure 1), showing it to be related to other natural products that possess the vicinal amino alcohol moiety. Using a chiral-synthon approach, (R)-(−)-complanine

• turned to its conversion to amino alcohol 4. It was envisioned that such conversion could be effected in a one-pot reaction by employing lithium aluminium hydride reduction of an aldoximine [5], formed in situ by condensation of a suitably oxygenated aldehyde 5 with hydroxylamine hydrochloride (Scheme 3

Exploring chemical diversity via a modular reaction pairing strategy

• Joanna K. Loh,
• Sun Young Yoon,
• Thiwanka B. Samarakoon,
• Alan Rolfe,
• Patrick Porubsky,
• Benjamin Neuenswander,
• Gerald H. Lushington and
• Paul R. Hanson

Beilstein J. Org. Chem. 2012, 8, 1293–1302, doi:10.3762/bjoc.8.147

• nucleophilic aromatic substitution (SNAr) diversification pathway is reported. Eight benzofused sultam cores were generated by means of a sulfonylation/SNAr/Mitsunobu reaction pairing protocol, and subsequently diversified by intermolecular SNAr with ten chiral, non-racemic amine/amino alcohol building blocks

Partial thioamide scan on the lipopeptaibiotic trichogin GA IV. Effects on folding and bioactivity

• Marta De Zotti,
• Barbara Biondi,
• Cristina Peggion,
• Matteo De Poli,
• Haleh Fathi,
• Simona Oancea,
• Claudio Toniolo and
• Fernando Formaggio

Beilstein J. Org. Chem. 2012, 8, 1161–1171, doi:10.3762/bjoc.8.129

• -terminal 1,2-amino alcohol leucinol (Lol) by the corresponding α-amino methyl ester (Leu-OMe) alters only slightly the biophysical and biological properties of trichogin GA IV. Conversely, we showed that the Nα-blocking fatty acyl moiety plays a major role in its membrane permeability and antibiotic

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

• antagonists of the human M1 muscarinic receptor; and a cellular assay to identify human immunodeficiency virus 1 inhibitors. Amino alcohol 9{7} was tested in 185 bioassays reported in PubChem, and found to serve as an inhibitor of human platelet activating factor acetylhydrolase 2 (PAFAH2). It is clear from

• . Relative energies of alkene isomers based on RB3LYP/6-311G* calculations with MacSpartan ’06. X-Ray structure of epoxyalcohol 6. Amine building blocks for library synthesis. X-ray structure of amino alcohol 10{7}. Formation of isomerized azepinoisoindoline 3 and oxirane 5. Ring-closing metathesis of diene

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• monitoring. However, the attempted isolation and purification of this compound by column chromatography provided amino alcohol 17 as the only product in high yield (92%). The limited stability of the TMS protective group is evident from the results presented in Scheme 7. Treatment of freshly prepared

• difficulties, tert-butyldimethylsilyl-protected compound 27 was prepared. Samarium diiodide-mediated ring opening under standard conditions furnished the expected amino alcohol 28 in excellent yield (Scheme 8). An attempted cyclisation of 28 using tosyl chloride in the presence of triethylamine was not