Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• , ii) a stereoselective N-glycosylation process that is compatible with an enantiomerically pure substrate, and iii) separation of enantiomers by chemical or enzymatic resolution methods. This review summarizes the methods used to synthesize 1,3-oxathiolane nucleosides. Many methods provide the

• intermediate 37 was resolved using a lipase in t-BuOMe, resulting in a high enantiomeric excess. They used an enzymatic resolution of an acetoxy sulfide with a Pseudomonas fluorescens lipase to obtain compound 38. Reaction of chiral acetoxy sulfide 38 with HCl in dry ethanol induced acetate removal by

• compound 41a as 1:1 mixture of cis- and trans-isomers. In 1995, Cousins and co-workers [49] investigated enzymatic methods to resolve an oxathiolane intermediate (Scheme 11). Racemic intermediate 42 was converted into 43 with propionyl chloride protection. The procedure provides the enzymatic resolution of

Kinetics of enzyme-catalysed desymmetrisation of prochiral substrates: product enantiomeric excess is not always constant

• Peter J. Halling

Beilstein J. Org. Chem. 2021, 17, 873–884, doi:10.3762/bjoc.17.73

• the equilibrium constant where the enzymatic reaction was not completely irreversible [2]. A limitation of the enzymatic resolution is that the maximum yield of the desired enantiomer is the 50% contained in the starting racemate. This is one reason for the current greater interest in enzymatic

The preparation and properties of 1,1-difluorocyclopropane derivatives

• Kymbat S. Adekenova,
• Peter B. Wyatt and
• Sergazy M. Adekenov

Beilstein J. Org. Chem. 2021, 17, 245–272, doi:10.3762/bjoc.17.25

• hydrogenation of difluorocyclopropenes [73][79]. Enzymatic hydrolysis or esterification: The first example of the enzymatic resolution of gem-difluorocyclopropanes was reported by Itoh et al. [80]. The prochiral diacetate of cis-1,2-bis-(hydroxymethyl)-3,3-difluorocyclopropane was converted into the

Synthesis of 2-aminosuberic acid derivatives as components of some histone deacetylase inhibiting cyclic tetrapeptides

• Shital Kumar Chattopadhyay,
• Suman Sil and
• Jyoti Prasad Mukherjee

Beilstein J. Org. Chem. 2017, 13, 2153–2156, doi:10.3762/bjoc.13.214

• [5][6]. For this, and other reasons, several synthetic routes to Asu have been developed [7][8][9] which often uses chemical or enzymatic resolution of a racemate [10]. However, the chemical synthesis of an orthogonally protected Asu derivative from easily available sources [11] for potential

Correction: Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 2128–2130, doi:10.3762/bjoc.13.210

• . Universidad 1001, Cuernavaca, Morelos, 62210, Mexico El Colegio Nacional, Luis Gonzáles Obregón 23, Centro Histórico, Ciudad de México, 06020, Mexico 10.3762/bjoc.13.210 Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic resolution; mechanochemistry; The original published Tables

• under ball milling. Substrate scope for the enzymatic resolution of N-benzylated-β3-amino esters. Recycling capacity of immobilized CALB under HSBM conditions. Scaling-up of the enzymatic hydrolysis reaction under ball-milling using substrate rac-1a. Supporting Information Supporting Information File

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• resolution of racemic β3-amino esters employing Candida antarctica lipase B (CALB) to afford highly valuable enantioenriched N-benzylated-β3-amino acids in good yields. Furthermore the present protocol is readily scalable. Keywords: ball-milling; β3-amino acid; Candida antarctica lipase B; enzymatic

• that led to the best results in the enzymatic resolution of substrate rac-1a (Table 1, entry 3) were employed with other racemic N-benzylated-β3-amino esters as substrates (Table 2). It can be appreciated that reaction yields decrease when longer aliphatic chains are present in the substrate (Table 2

• enzymatic hydrolysis of racemic β3-amino ester rac-1a using CALB in solution [52] (top) and under HSBM conditions (button). 2M2B: 2-methyl-2-butanol. Search of the best parameters in the enzymatic enantioselective hydrolysis of rac-1a under ball milling. Substrate scope for the enzymatic resolution of N

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• synthesis of this interesting drug has attracted great attention, especially asymmetric synthesis approaches. However, only a few methods have been reported for the synthesis of enantiopure dapoxetine hydrochloride. The earlier methods included chiral/enzymatic resolution [5], whereas the newer approaches

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• classical resolution [41], enzymatic resolution in conjunction with HPLC [42], or HPLC separation of derived peptides [43], preparative HPLC separation on a chiral phase column [44], asymmetric synthesis from chiral precursors [45][46] including the stereoselective alkylation of aromatic compounds with

Stereoselectively fluorinated N-heterocycles: a brief survey

• Xiang-Guo Hu and
• Luke Hunter

Beilstein J. Org. Chem. 2013, 9, 2696–2708, doi:10.3762/bjoc.9.306

• then furnished rac-4b, the substrate for enzymatic resolution. Using an immobilized lipase enzyme as the catalyst (and under slightly different conditions from those described in Scheme 1), one enantiomer of the racemic β-lactam 4b was completely transformed into the ester 5b, while the other

Chemoenzymatic synthesis and biological evaluation of enantiomerically enriched 1-(β-hydroxypropyl)imidazolium- and triazolium-based ionic liquids

• Paweł Borowiecki,
• Małgorzata Milner-Krawczyk and
• Jan Plenkiewicz

Beilstein J. Org. Chem. 2013, 9, 516–525, doi:10.3762/bjoc.9.56

• bacteria and fungi. Results and Discussion Synthesis and enzymatic resolution of the N-2-hydroxypropylazoles In this paper we report the synthesis of racemic 1-(1H-imidazol-1-yl)propan-2-ol and 1-(1H-1,2,4-triazol-1-yl)propan-2-ol and the procedure for lipase-catalyzed kinetic separation of their

Metathesis access to monocyclic iminocyclitol-based therapeutic agents

• Ileana Dragutan,
• Valerian Dragutan,
• Carmen Mitan,
• Hermanus C.M. Vosloo,
• Lionel Delaude and
• Albert Demonceau

Beilstein J. Org. Chem. 2011, 7, 699–716, doi:10.3762/bjoc.7.81

• both during ester group reduction and the subsequent steps. By a similar approach (Scheme 4), these authors also obtained the enantiopure homoiminocyclitol (−)-(2S,3R,4S,5S)-2,5-dihydroxymethylpyrrolidin-3,4-diol (23). Starting from the same racemic vinyl glycine methyl ester and introducing enzymatic

• resolution in the ester reduction step, enantiopure (+)-21 was obtained. 1st-generation Grubbs catalyst was used for the RCM of (+)-21. It should be noted that the yield of (+)-22 in RCM (10 mol % 2, in benzene) was temperature dependent (88% at room temperature and 98% at 80 °C). Further stereocontrolled

Oxidative allylic rearrangement of cycloalkenols: Formal total synthesis of enantiomerically pure trisporic acid B

• Silke Dubberke,
• Muhammad Abbas and
• Bernhard Westermann

Beilstein J. Org. Chem. 2011, 7, 421–425, doi:10.3762/bjoc.7.54

• the synthesis of natural occurring terpenes, i. a., trisporic acid and its derivatives. An advanced building block has been synthesized in a short reaction sequence, which involves an oxidative allylic rearrangement initiated by pyridinium dichromate (PDC) as the key step. Keywords: enzymatic

• resolution; natural products; oxidative rearrangement; pig liver esterase (PLE); trisporic acid B; Introduction The generation of chiral, non-racemic compounds bearing a stereogenic quaternary carbon centre is of great interest [1][2][3][4][5][6][7][8]. Therefore, much effort has been directed towards the

Development of dynamic kinetic resolution on large scale for (±)-1-phenylethylamine

• Lisa K. Thalén and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2010, 6, 823–829, doi:10.3762/bjoc.6.97

• enzyme can be used for practical DKR of benzylic amines [14][15][16], while the Kim and Park group have combined a palladium nanocatalyst with an enzyme for the DKR of amines [17]. Additional procedures for the chemoenzymatic DKR of amines in which various racemization methods are combined with enzymatic

• resolution have been established [18][19][20][21][22][23]. We herein report the evaluation of our system for application on multigram scale. Results and Discussion The previously reported [12][13] protocol for application of DKR on a 0.5 mmol scale was evaluated with the aim of developing a system that could

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

• (Scheme 15). The results were found to be similar to the batch results where steady emulsions were formed. Up to 58 reactions were performed serially within 4 h, requiring a total of only 150 μL of cell lysate. Numerous applications involving the enzymatic resolution of racemic substrates in flow devices

Large- scale ruthenium- and enzyme- catalyzed dynamic kinetic resolution of (rac)-1-phenylethanol

• Krisztián Bogár,
• Belén Martín-Matute and
• Jan-E. Bäckvall

Beilstein J. Org. Chem. 2007, 3, No. 50, doi:10.1186/1860-5397-3-50

• aldehydes, [17][18] and asymmetric aldol reactions. [19][20][21][22][23] Biocatalysts have also been successfully employed in the enantioselective reduction of ketones.[24] The enzymatic resolution of racemic alcohols is a convenient alternative for preparing enantiomerically pure alcohols,[1][25][26][27

• ][28] and recently this approach has been extended to dynamic kinetic resolution (DKR) by combining the enzymatic resolution with a metal-catalyzed racemization. [29][30][31][32][33][34][35][36][37] Today, many stable lipases are commercially available and they are frequently used in synthetic organic

• organic solvents.[38][39] CALB is immobilized on polyacrylate and this increases its thermostability and makes it easy to recover from the reaction mixture. Recently, we have developed highly efficient DKR protocols for secondary alcohols in which the traditional enzymatic resolution is combined with an