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

Stereogenic boron in 2-amino-1,1-diphenylethanol-based boronate–imine and amine complexes

• Sebastian Schlecht,
• Walter Frank and
• Manfred Braun

Beilstein J. Org. Chem. 2011, 7, 615–621, doi:10.3762/bjoc.7.72

• known procedure [20], the amino alcohol 5 was readily accessible from methyl glycinate hydrochloride by the reaction with excess phenylmagnesium bromide. Subsequent condensation with 1-formyl-2-naphthol (6) gave the imine 7 in 87% yield (Scheme 2). In order to generate the boronate–imine complex 8, the

• . HPLC was performed with the chiral column CHIRALPAK IB. Toluene was freshly distilled from sodium under a nitrogen atmosphere. 1-{[(2-Hydroxy-2,2-diphenylethyl)imino]methyl}naphthalen-2-ol (7) A mixture of amino alcohol 5 (0.427 g, 2.00 mmol), naphthaldehyde 6 (0.379 g, 2.20 mmol), and sodium sulfate

Application of the diastereoselective photodeconjugation of α,β-unsaturated esters to the synthesis of gymnastatin H

• Ludovic Raffier and
• Olivier Piva

Beilstein J. Org. Chem. 2011, 7, 151–155, doi:10.3762/bjoc.7.21

• enantioselective versions. Starting from α-substituted esters 3 in the presence of a catalytic amount of an enantiomerically pure bicyclic amino alcohol 4 – derived from camphor –, the protonation of the prochiral photodienol can be achieved with an ee up to 91% [5]. This value is one of the highest values

• ]. In this context, we have considered an alternative synthetic route to the fatty acid common to all gymnastatins according to a photoisomerisation–diastereoselective protonation sequence involving catalytic amounts of an achiral organocatalyst (e.g., amino alcohol 4b). Our goal was to describe the

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• or BF3•Et2O in CH2Cl2; aminolytic kinetic resolution [12][38]), and use of (Me3)SiHNPO(OEt)2 [39] also proved ineffective. A convenient asymmetric access was eventually developed, starting with ring-opening of commercially available (R)-1,2-epoxybutane (15) using ammonia, which gave β-amino alcohol

Oxalyl retro-peptide gelators. Synthesis, gelation properties and stereochemical effects

• Janja Makarević,
• Milan Jokić,
• Leo Frkanec,
• Vesna Čaplar,
• Nataša Šijaković Vujičić and
• Mladen Žinić

Beilstein J. Org. Chem. 2010, 6, 945–959, doi:10.3762/bjoc.6.106

• represents the major organizational element in the gel assemblies of both, bis(amino acid)- and bis(amino alcohol)oxalamides, and also has the major influence on their organization in the solid state [55][56][57][58][59][60]. In addition, the latter gelators tend to exhibit layered organization in their gel

• strongly influence both, gelation effectiveness and the morphology characteristics of gel network. Chiral bis(amino acid)-(I) and bis(amino alcohol)-(II)-oxalamide gelators. TEM images (PWK staining) of: (S,S)-1a H2O/DMSO gel. TEM images (PWK staining) of: (S,R)-1a H2O/DMSO gel. TEM images (PWK staining

Formation of epoxide-amine oligo-adducts as OH-functionalized initiators for the ring-opening polymerization of ε-caprolactone

• Julia Theis and
• Helmut Ritter

Beilstein J. Org. Chem. 2010, 6, 938–944, doi:10.3762/bjoc.6.105

• catalytic transfer hydrogenation. Accordingly, 4-nitroanisole was reduced under microwave conditions to give 4-aminoanisole which reacted immediately with the diglycidyl ether of bisphenol A in an addition polymerization reaction to yield oligo(amino alcohol)s. The hydroxy groups of the new formed oligomers

• former work on the formation of hyperbranched epoxide-amine adducts via microwave-assisted heterogeneous catalytic transfer hydrogenation [22], we report herein the synthesis of an linear oligo(amino alcohol). The hydroxy groups of the latter were then used as an initiator for the ring-opening

• by the complete disappearance of the absorption band at 911 cm−1 associated with the C–H stretching vibration of the epoxide group. Furthermore, the formation of amino alcohol units was confirmed by the appearance of a broad band in the range of 3600–3150 cm−1 with a maximum at 3370 cm−1

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Concise methods for the synthesis of chiral polyoxazolines and their application in asymmetric hydrosilylation

• Wei Jie Li,
• Zun Le Xu and
• Sheng Xiang Qiu

Beilstein J. Org. Chem. 2010, 6, No. 29, doi:10.3762/bjoc.6.29

• analytical grade. Syntheses of polyoxazoline ligands 3,4-Dihydroxy-2,5-bis(4-substituted-oxazolin-2-yl)furan Method A: 3,4-Dihydroxyfuran-2,5-dicarboxylic acid (0.75 g, 4.0 mmol), the chiral amino alcohol (8.8 mmol) and toluene (40 mL) were placed in a three-neck flask, fitted with a water segregator, a

• desired compound. Method B: 0.87 g (4.0 mmol) of dimethyl-3,4-dihydroxyfuran-2,5-dicarboxylate, 8.0 mmol of the chiral amino alcohol and 40 mL of toluene were added to a three-neck flask equipped with a water segregator, a reflux condenser and a magnetic stirring bar. The mixture was heated under reflux

Synthesis of a new class of aminocyclitol analogues with the conduramine D-2 configuration

• Latif Kelebekli,
• Yunus Kara and
• Murat Celik

Beilstein J. Org. Chem. 2010, 6, No. 15, doi:10.3762/bjoc.6.15

• diols in the presence of p-toluenesulfonyl isocyanate for the introduction of the amino alcohol functionality. We are currently interested in the synthesis of cyclitols and their derivatives [25]. As a part of our program directed towards the synthesis of potential glycosidase inhibitors we used a

• % yield. The introduction of the amino alcohol functionality was achieved by a regio- and stereoselective Pd(0) catalyzed reaction of diol 11 and TsNCO [32]. Thus treatment of the cis-diol 11 in THF with 2 equiv of p-toluenesulfonyl isocyanate gave the corresponding bis-carbamate 12 which was subsequently

Continuous flow enantioselective arylation of aldehydes with ArZnEt using triarylboroxins as the ultimate source of aryl groups

• Julien Rolland,
• Xacobe C. Cambeiro,
• Carles Rodríguez-Escrich and
• Miquel A. Pericàs

Beilstein J. Org. Chem. 2009, 5, No. 56, doi:10.3762/bjoc.5.56

• flow system for the synthesis of enantioenriched diarylmethanols from aldehydes is described. The system uses an amino alcohol-functionalized polystyrene resin as the catalyst, and the arylating agent is conveniently prepared by transmetallation of triarylboroxins with diethylzinc. Keywords

• reaction, although usually at the cost of low catalytic activity, high catalytic loadings being required for the achievement of satisfactory yields [14][15]. In contrast, β-amino alcohol 1 (Figure 2), developed in our laboratory [16], showed high activity and enantioselectivity in the ethylation [16

• mmol) in toluene (33 mL), was connected to one of the pumps, at 0.12 mL·min−1, while toluene (0.12 mL·min−1) was kept in the other one, and the column was cooled down to 10 °C. These conditions were kept for a further 1 h, in order to form the amino alcohol-Zn complex. Then, a 0.61 M solution of

Asymmetric reactions in continuous flow

• Xiao Yin Mak,
• Paola Laurino and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2009, 5, No. 19, doi:10.3762/bjoc.5.19

• flow process for the addition of diethylzinc to various aldehydes was described recently (Scheme 4) [27]. Reagent solutions were fed by piston-pump driven flow through a fritted column packed with chiral amino-alcohol functionalized Merrifield resin 9. Under optimal conditions (10 °C, a flow rate of

• drops during flow-through that can often be problematic with gel-type resins. The flexibility and ease for adjusting porosity, composition and shape of these materials is an additional advantage [37][38]. The monolith-supported chiral amino alcohol catalyst 29 has been developed for the enantioselective

• flow. Asymmetric synthesis of ß-lactams. α-Chlorination of acid chlorides in flow. Asymmetric Michael reaction in continuous flow. Enantioselective addition of Et2Zn to benzaldehyde using monolithic chiral amino alcohol. Continuous-flow hydrolytic dynamic kinetic resolution of epibromohydrin (32

(−)-Complanine, an inflammatory substance of marine fireworm: a synthetic study

• Kazuhiko Nakamura,
• Yu Tachikawa and
• Daisuke Uemura

Beilstein J. Org. Chem. 2009, 5, No. 12, doi:10.3762/bjoc.5.12

• was then subjected to acidic deprotection to afford the diol 6 in 43% yield (2 steps). The primary alcohol was converted into the azide via the mesylate (79%), which was then successfully converted into the corresponding amino alcohol 7 (78%). From a spectral perspective, the amino alcohol 7 was

• , CH3CN, rt, 24 h) [9]. A reaction occurred between the amino alcohol and the activated ester (2.0 equiv) in MeOH to give the desired (−)-complanine in 44% yield. The synthesized product was identical to the natural material in all its spectral data, including optical rotation ([α]D20 = −9.9 (c 0.12, H2O

• )). The configuration of the hydroxy-substituted carbon atom was determined to be R. The configuration is comparable to that of the related compound, obscuraminol, isolated from an ascidian from Tarifa Island, Spain. Obscuraminol possesses a vic-amino alcohol and an unsaturated carbon chain; its absolute

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• synthesis before the introduction of other incompatible functional groups (lactam, thiolactam, enaminone). The only feasible option was to go back to the chiral amine (+)-14, reduction of which with lithium aluminium hydride gave the unstable amino alcohol (+)-30 in 97% yield as long as the amine was added

• slowly to a stirred suspension of the hydride in diethyl ether (Scheme 4). If the order of addition were reversed, the best yield obtained was 48%. The amino alcohol was protected as its tert-butyl(dimethyl)silyl ether (−)-31 (99%) before hydrogenolysis of the benzyl groups over Pearlman's catalyst in

A divergent asymmetric approach to aza-spiropyran derivative and (1S,8aR)-1-hydroxyindolizidine

• Jian-Feng Zheng,
• Wen Chen,
• Su-Yu Huang,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2007, 3, No. 41, doi:10.1186/1860-5397-3-41

• procedure, namely, N-debenzylation/O-mesylation/Boc-cleavage/cyclization, and O-debenzylation. Alternatively, amino alcohol 8 was mesylated and the resultant mesylate 12 was subjected to hydrogenolytic conditions, which gave (1S,8aR)-1-hydroxyindolizidine (ent-3) in 60% overall yield from 8. Conclusion By

• -cleavage/cyclication, and O-debenzylation. In searching for a more concise method, amino alcohol 8 was mesylated (MsCl, NEt3, 0 °C) and the resultant labile mesylate 12 was subjected to catalytic hydrogenolysis (H2, l atm, 10% Pd/C, r.t.), which gave (1S,8aR)-1-hydroxyindolizidine (ent-3) in 60% overall

• . Stereoselective synthesis of (1S,8aR)-1-hydroxyindolizidine (ent-3). One-pot synthesis of ent-3 from amino alcohol 8. Supporting Information Supporting Information File 94: Experimental. Experimental procedures for the synthesis of all compounds described, and characterization data for the synthesized compounds

The enantiospecific synthesis of (+)-monomorine I using a 5-endo- trig cyclisation strategy

• Malcolm B. Berry,
• Donald Craig,
• Philip S. Jones and
• Gareth J. Rowlands

Beilstein J. Org. Chem. 2007, 3, No. 39, doi:10.1186/1860-5397-3-39

• synthesis of (+)-monomorine I, the initial target, pyrrolidine 22, was prepared. Commercially available D-norleucine was reduced to the amino alcohol 17. [19] This was then converted into the benzoyl-protected aminosulfone 20 via the diphenylphosphinylaziridine 18, which was ring-opened to give 19, followed

Pd-catalysed [3 + 3] annelations in the stereoselective synthesis of indolizidines

• Olivier Y. Provoost,
• Andrew J. Hazelwood and
• Joseph P. A. Harrity

Beilstein J. Org. Chem. 2007, 3, No. 8, doi:10.1186/1860-5397-3-8

• modification of the route described by Righi and co-workers [11]. Accordingly, tosyl protection of (R)-serine 5 followed by esterification and TBDPS-protection provided 6 in good overall yield. Ester reduction was carried out conveniently on multigram scale using LiBH4 to give an amino alcohol that was

Synthesis and glycosidase inhibitory activity of new hexa- substituted C8-glycomimetics

• Olivia Andriuzzi,
• Christine Gravier-Pelletier,
• Gildas Bertho,
• Thierry Prangé and
• Yves Le Merrer

Beilstein J. Org. Chem. 2005, 1, No. 12, doi:10.1186/1860-5397-1-12

• hands, we next turned to the obtention of C8-aminocyclitols. Thus, reduction of the azido group of 11 by dihydrogen in the presence of palladium black in ethyl acetate (Scheme 3) afforded the amino-alcohol 13 which could be submitted to acidic hydrolysis of the O-protective groups to give, after

Methods for the synthesis of polyhydroxylated piperidines by diastereoselective dihydroxylation: Exploitation in the two-directional synthesis of aza-C-linked disaccharide derivatives

• Andrew Kennedy,
• Adam Nelson and
• Alexis Perry

Beilstein J. Org. Chem. 2005, 1, No. 2, doi:10.1186/1860-5397-1-2

• configurations may be easily prepared. Our synthetic strategy is outlined in Scheme 1. We have previously shown that the configuration of 1,3-amino alcohol derivatives, such as 10, may be controlled by the addition of a lithium enolate to an N-sulfinyl imine (→ 9, for example) and diastereoselective reduction

• (Scheme 2).[24][25][26][27][28][29][30][31][32] Two-directional[33] oxidative ring expansion of 1,3-difuryl 1,3-amino alcohol derivatives 4 would yield a densely functionalised bis-enone which would be ripe for further functionalisation. The term "two-directional synthesis" is usually used to describe the

• materials were prepared from the 1,3-amino alcohol derivatives 1,3syn- and 1,3anti-10 (Scheme 6). Treatment of the difuryl 1,3-sulfinimido alcohols 1,3syn- and 1,3anti-10 with NBS in buffered THF-water precipitiated sulfonamide oxidation and two-directional ring expansion of both furan rings;[50] the crude