Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• vibralactone, a potent inhibitor of pancreatic lipase, is reported. The synthesis of the challenging all-carbon quaternary center within the cyclopentene ring was achieved through intramolecular alkylidene carbene C–H insertion. Keywords: alkylidene carbene; C–H insertion; total synthesis; vibralactone

• channels [13]. Tetrahydrolipstatin (5) is a potent pancreatic lipase inhibitor and has been developed into an antiobesity drug marketed under the generic name Orlistat. Vibralactone (6), which was isolated by Liu and co-workers from Basidiomycete Boreostereum vibrans, features a fused β-lactone with a

• cyclopentene ring containing an all-carbon quaternary center [14], and inhibits pancreatic lipase with an IC50 of 0.4 µg/mL. Several congeners with varying oxidation state, as well as related β-hydroxy acids or esters have also been isolated from the culture broth of the basidiomycete [15][16][17][18][19][20

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• general mechanism of a reaction catalyzed by lipases is illustrated in Scheme 1. Additionally, the diverse three-dimensional structures of lipases confer enantioselectivity in lipase-catalyzed esterification [24][25]. Moreover, their commercial availability makes lipases an attractive option for preparing

• optically pure intermediates in total synthesis. This section focuses on applications of lipase-catalyzed acylation of prochiral 1,3-diols in total synthesis. Porcine pancreatic lipase (PPL) PPL, a commercially available lipase isolated from fresh porcine pancreas [26], is one of the most widely used

• in two steps. Subsequently, asymmetric acetylation of 2 catalyzed by PPL afforded (R)-3 in 95% yield with 83% ee. The authors also used Candida antarctica lipase (CAL) in this transformation but with a suboptimal result ((S)-3 in 19% yield with 94% ee). The monoacetate (R)-3 was further converted

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• Mannich reactions [20], lipase-catalyzed esterification [21], nitro-aldol [22], Michael [23], and aza-Michael reactions [24][25], Diels–Alder reactions [26][27] and Friedel–Crafts alkylation of indoles [28]. Many high pressure reactions were applied in natural product synthesis [29]. The high pressure

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• with vinyl acetate as the acylating agent, Amano lipase AK (AKL) was identified as the most effective biocatalyst for achieving selective acetylation, converting diol 28 to the monoacetate 37 in 91% yield with >99.4% de (by HPLC). The diacetate byproduct 39 was formed in a small amount (9%). A similar

• diol desymmetrization of ent-28 was best achieved with Amano lipase PS (PSL), yielding monoacetate ent-37 (de 99.6%, 93% yield) without the formation of diacetate ent-39. Compound 37 was tosylated using tosyl chloride in pyridine with the addition of DMAP and the resulting product was treated with

• alcohol as a THP ether. Yadav and Yadav commenced their synthesis with the enzymatic desymmetrization of meso-diol 67 to monoacetate 66, achieving a 47% yield with an enantiomeric excess greater than 95%, using porcine pancreatic lipase (PPL) and vinyl acetate in THF (Scheme 10). The remaining primary

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• (R)-citronellic acid [18], methyl (S)-3-hydroxy-2-methylpropanoate, (S)-2-methyl-1-butanol [19], (R)-2,3-O-isopropylideneglyceraldehyde [20], (R)- and (S)-citronellol [21], (R)-4-methyl-δ-valerolactone [22], porcine pancreatic lipase (PPL)-catalyzed acetylation of racemic citronellol [23], and Evan′s

Natural resorcylic lactones derived from alternariol

• Joachim Podlech

Beilstein J. Org. Chem. 2024, 20, 2171–2207, doi:10.3762/bjoc.20.187

• especially active against the kinase pp60c-Src (IC50: 20 nM) [231]. Altenusin turned out to be an inhibitor of α-glucosidase and pancreatic lipase (IC50: 46.1, 21.5 µM, respectively) [238], and of neutral sphingomyelinase (nSMase) with an IC50 value of 28 µM (but not of aSMase) [230][239]. It inhibited tau

The Groebke–Blackburn–Bienaymé reaction in its maturity: innovation and improvements since its 21st birthday (2019–2023)

• Cristina Martini,
• Muhammad Idham Darussalam Mardjan and
• Andrea Basso

Beilstein J. Org. Chem. 2024, 20, 1839–1879, doi:10.3762/bjoc.20.162

• et al. reported the first biocatalytic GBB reaction using lipase [21]. The model reaction depicted in Scheme 2 (R = t-Bu) was tested in ethanol at room temperature with various enzymes, where Candida antarctica lipase B (CALB) and Aspergillus niger gave best results, affording 3 in 63% and 64% yields

Polymer degrading marine Microbulbifer bacteria: an un(der)utilized source of chemical and biocatalytic novelty

• Weimao Zhong and
• Vinayak Agarwal

Beilstein J. Org. Chem. 2024, 20, 1635–1651, doi:10.3762/bjoc.20.146

• -fructofuranosidase were expressed in E. coli [41]. Both enzymes can work together to effectively degrade inulin. Lipases are enzymes that can hydrolyze various fatty esters and find applications in the detergent, oil, and pharmaceutical industries. The lip4346 is a novel lipase-encoding gene cloned from the

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• group where an immobilized lipase (e.g., CALB) facilitated the derivatization of high-boiling benzyl alcohol in scaled Curtius rearrangement reactions. Ultimately, this approach negated the use of column chromatography in favor of a simple trituration process to isolate pure carbamate products [106

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• stereoselective kinetic resolution of allenol 3 via lipase AK-catalyzed acetylation [15]. In this way, unaltered, (−)-hydroxyallene 3 could be separated from (+)-acetyl derivative 9 through standard column chromatography (Scheme 3). Enantiomeric excesses of (−)-3 and (+)-9 were determined by chiral HPLC analyses

• ) AgNO3, Me2CO, 75%. Racemic resolution of allenol 3 and synthesis of derivatives. a) Lipase AK, vinyl acetate, t-BuOMe, 30 °C, ((−)-(S)-3: 46%, 90% ee, (+)-(R)-9: 39%, 95% ee); b) N,N’-dicyclohexylcarbodiimide (DCC), dimethylaminopyridine (DMAP), (S) or (R)-(−)-α-methoxy-α-(trifluoromethyl)phenylacetic

Synthesis of odorants in flow and their applications in perfumery

• Merlin Kleoff,
• Paul Kiler and
• Philipp Heretsch

Beilstein J. Org. Chem. 2022, 18, 754–768, doi:10.3762/bjoc.18.76

• a method for the acetylation of isoamyl alcohol (9) catalyzed by Candida antarctica lipase B (Scheme 3) [26]. A biphasic system consisting of n-heptane and an aqueous buffer solution is used and efficiently mixed in a Corning AFRTM Low Flow reactor providing a fine dispersion of the reaction mixture

• and, thus, a large interface between the phases. Subsequently, the biphasic system is directly separated, employing a PTFE membrane separator, to afford a solution of isoamyl acetate in n-heptane, while the aqueous layer containing the lipase could be recycled. At 60 °C with a residence time of 8.6

• layer is mixed with vinyl acetate (53) and pumped through a column reactor containing Candida antarctica lipase A. At 30 °C and with a residence time of 11 min, acetylation of cis-alcohol 52 is mediated. After distillation, cis-woody acetate 54 is obtained in 89% isolated yield (de > 99%) on a gram

Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

• Sandeep Kumar,
• Jyotirmoy Maity,
• Banty Kumar,
• Sumit Kumar and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2022, 18, 95–101, doi:10.3762/bjoc.18.10

• % overall yield starting from compound 11, respectively (Scheme 2). The use of lipase as biocatalyst was employed for the selective acetylation of the primary hydroxy group present in trihydroxy nucleosides 14a,b. This led to the screening of two different lipases, viz Candida antarctica lipase-B (CAL-B

• ) immobilized on polyacrylate (Lewatit), commonly known as Novozyme® 435 and Thermomyces lanuginosus lipase immobilized on silica, commonly known as Lipozyme® TL IM in different organic solvents, such as THF, acetonitrile, toluene, acetone, DIPE and 2-Me-THF. Vinyl acetate was used as acetyl donor at

• reusability of the recovered Lipozyme® TL IM was also checked and it was found that the lipase could be used up to seven cycles of selective acetylation of 3′-azido-3′-deoxy-β-ᴅ-allofuranosyl nucleosides 14a,b without noticeable loss of regioselectivity and efficiency. Thus, trihydroxy nucleosides 14a,b were

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

• 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

• oxathiolane propionate derivative 43 by using Mucor miehei lipase, which affords (−)-enantiomer 44 as residual substrate. This enantioenriched precursor was useful to obtain the pure corresponding nucleoside analogue. Faury and co-workers [50] synthesized the tetrazole analogues of 1,3-oxathiolane nucleosides

• -friendliness. Ren and colleagues [59] recently reported the preparation of an enantiopure 1,3-oxathiolane 65 utilizing a multienzymatic cascade protocol (Scheme 21). The combined use of surfactant-treated Subtilisin Carlsberg (STS) and Candida antarctica lipase B (CAL-B) resulted in the 1,3-oxathiolane ring in

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

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

• -reductases. The reductant (usually NADH or NADPH) has to bind first to the enzyme, followed by the prochiral ketone in the second step. The chiral products are then released before the oxidised co-product. “Ping-pong, second”. Followed by most transaminases and lipase or esterase-catalysed acylation of

• prochiral diols. The enzyme reacts with an amino or acyl donor, releasing a first co-product, to give an aminated or acylated enzyme intermediate. This then reacts with the prochiral ketone or diol to generate the chiral products. “Ping-pong, first”. Followed in most lipase or esterase hydrolyses of

• , both”. Followed in most lipase or esterase reactions of prochiral diacids: either hydrolysis of their esters, or esterification of the free acids. The enzyme reacts enantiospecifically with the ester or acid. But now the acyl enzyme can be in either stereoisomeric form, so the kinetics are different

Biochemistry of fluoroprolines: the prospect of making fluorine a bioelement

• Vladimir Kubyshkin,
• Rebecca Davis and
• Nediljko Budisa

Beilstein J. Org. Chem. 2021, 17, 439–460, doi:10.3762/bjoc.17.40

• subdomain [129], T. thermohydrosulfuricus lipase [130][131][132], human ubiquitin [133], single-chain Fv format protein [134], KlenTag DNA polymerase [135], thioredoxin A [120], β2-microglobulin [136], red fluorescent protein [137][138], Pin1 WW domain [139], bacteriophage T4 fibritin C-terminal domain [106

• Geobacillus thermoleovorans lipase (GTL) yielded a properly folded sample with R-Flp and an insoluble protein with S-Flp (Figure 14A). The lack of solubility in the latter case indicates critical folding issues induced by the presence of S-Flp in the sequence. With α-amylase from Pyrococcus woesei (PWA), the

Coupling biocatalysis with high-energy flow reactions for the synthesis of carbamates and β-amino acid derivatives

• Alexander Leslie,
• Thomas S. Moody,
• Megan Smyth,
• Scott Wharry and
• Marcus Baumann

Beilstein J. Org. Chem. 2021, 17, 379–384, doi:10.3762/bjoc.17.33

• within continuous flow processes [17][18][19][20] to provide a greener and more chemoselective means for the synthesis of drug-like targets. Recently, we reported on an innovative telescoped process using immobilized CALB (Candida antarctica lipase B) to enable the conversion of residual benzyl alcohol

Regioselective chemoenzymatic syntheses of ferulate conjugates as chromogenic substrates for feruloyl esterases

• Olga Gherbovet,
• Fernando Ferreira,
• Apolline Clément,
• Mélanie Ragon,
• Julien Durand,
• Sophie Bozonnet,
• Michael J. O'Donohue and
• Régis Fauré

Beilstein J. Org. Chem. 2021, 17, 325–333, doi:10.3762/bjoc.17.30

• ; hydrolysis; lipase; transesterification; Introduction The development of “white biotechnology” is underpinned by advances in enzyme discovery and engineering, areas that are being driven by metagenomics and in vitro-directed enzyme evolution. These techniques procure massive discovery or the creation of new

• in 56% in-house yield and in up to 77% previously reported yield [24][25] in one step on a gram scale) using Lipozyme® TL IM (a commercially available immobilized lipase from T. lanuginosus that efficiently catalyzes the transesterification of cinnamates) [26][27][28] and readily available and

• groups of the glycoside and the O-acetyl group of the ferulate moiety. The fact that lipase-catalyzed transesterification obviates the need for protection and deprotection is a considerable advantage because the final deprotection in the chemical pathway is complicated by the presence of another ester

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

• corresponding monoacetate through Alcaligenes sp. lipase-catalyzed hydrolysis with >99% enantiomeric excess. Kirihara et al. have reported the synthesis of the separate enantiomers of 2,2-difluoro-1-aminocyclopropanecarboxylic acid, which are analogs of the naturally occurring 1-aminocyclopropanecarboxylic acid

• [81]. The authors obtained the chiral monoacetate intermediates (R)-78 and (S)-80 by lipase-catalyzed methods. The lipase-catalyzed asymmetric transesterification of prochiral diol 77 and the deacetylation of the prochiral diacetate 79 resulted in the formation of the (R)-monoacetate (R)-78 and (S

• )-monoacetate (S)-80, respectively (Scheme 32). As for the transesterification, a high yield (96.5%) and enantioselectivity (91.3% ee) were obtained using lipase PS in benzene. In the case of the deacetylation, the use of Amano PS lipase in acetone gave a high yield (86.2%), enantioselectivity (91.7% ee), and

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• amination of the tetrahydropyranone 50 to generate the (all-cis)-tetrahydropyran fragment. This group reported multiple different routes to 50. In an abortive route, the addition of allyl-Grignard to 5-methylfurfural, followed by the resolution of the racemic homoallylic alcohol with Amano lipase gave

Synthesis of new dihydroberberine and tetrahydroberberine analogues and evaluation of their antiproliferative activity on NCI-H1975 cells

• Giacomo Mari,
• Lucia De Crescentini,
• Serena Benedetti,
• Francesco Palma,
• Stefania Santeusanio and
• Fabio Mantellini

Beilstein J. Org. Chem. 2020, 16, 1606–1616, doi:10.3762/bjoc.16.133

• effects [32], inhibits both hERG current and the expression of hERG protein [33], inhibits the pancreatic lipase [34], shows antiradical, revitalizing and antifibrotic properties for dermatological applications [35], manifests a synergic effect with antibiotics [36], and displays antitumoral activities

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

• synthesis of the title compound has been developed using an efficient and highly enantioselective lipase-catalyzed acylation in a hydrophobic ionic liquid, [bmim][PF6], followed by a diastereoselective asymmetric dihydroxylation as the key steps for incorporating the stereogenic centers. The further

• conversion to the appropriate intermediates and subsequent acylation with lauric acid furnished the target compound. Keywords: AD mix-β; [bmim][PF6]; DDQ; HPA-12; lipase; Introduction Ceramides belong to the family of sphingolipids (SLs) and are synthesized de-novo in the endoplasmic reticulum (ER) [1

• ]. Our group has been using lipases for the chemoenzymatic syntheses of several bioactive molecules [34][35][36][37][38][39]. The prevalence of PhCH(OH) in 2, and in many other biochemicals, attracted our attention to formulate an enantioselective lipase-catalyzed transacetylation strategy to obtain a