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Search for "debenzylation" in Full Text gives 63 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis of ether lipids: natural compounds and analogues
- Marco Antônio G. B. Gomes,
- Alicia Bauduin,
- Chloé Le Roux,
- Romain Fouinneteau,
- Wilfried Berthe,
- Mathieu Berchel,
- Hélène Couthon and
- Paul-Alain Jaffrès
Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96
- the alcoholate reacted with 1-iodohexadecane to produce 3.3 in 50% yield. The phosphocholine moiety was incorporated by using 2-bromoethyl dichlorophosphate as a key reagent and following a previously reported sequence [67]. The debenzylation by using hydrogenolysis conditions produced 3.5 in 75% to
- benzylation produced 4.13. Then, the deprotection of the primary alcohol in acidic conditions allows introducing the phosphocholine polar head group by using POCl3 and the choline tosylate salt as reagents to yield 4.14. Finally, the debenzylation of the secondary alcohol and its acylation produce PAF 4.15. b
- ) The second scheme is shorter (Figure 4D) and starts with the acylation of 4.16 to produce 4.17. Then, the debenzylation of the primary alcohol produced 4.18. Interestingly, the migration of the acetyl group from sn-2 to sn-3 position was not observed. Finally, the installation of the phosphocholine
Graphical Abstract
Figure 1: Chemical structure of some natural ether lipids (ELs).
Figure 2: Synthesis of lyso-PAF and PAF from 1-O-alkylglycerol [64].
Figure 3: Synthesis of lyso-PAF from 1,3-benzylideneglycerol 3.1 [69].
Figure 4: A) Synthesis of the two enantiomers of octadecylglycerol (4.6 and 4.10) from ᴅ-mannitol (4.1); B) s...
Figure 5: Four-step synthesis of PAF 5.6 from (S)-glycidol [73].
Figure 6: Synthesis of 1-O-alkylglycerol A) from solketal, B) from ᴅ- or ʟ-tartaric acid and the intermediate ...
Figure 7: Synthesis of EL building blocks starting from substituted glycidol 7.1a–c [82].
Figure 8: Synthesis of PAF 8.5 by using phosphoramidite 8.2 [86].
Figure 9: Synthesis of oleyl-PAF 9.7 from ʟ-serine [88].
Figure 10: Synthesis of racemic analogues of lyso-PAF 10.8 and PAF 10.9 featuring a phenyl group between the g...
Figure 11: Synthesis of racemic deoxy-lyso-PAF 11.7 and deoxy-PAF 11.8 [91].
Figure 12: Synthesis of racemic thio-PAF 12.8 [93].
Figure 13: Racemic synthesis of 13.6 to illustrate the modification of the glycerol backbone by adding a methy...
Figure 14: Racemic synthesis of 14.5 as an illustration of the introduction of methyl substituents on the glyc...
Figure 15: Synthesis of functionalized sn-2-acyl chains of PC-EL; A) Steglich esterification or acylation reac...
Figure 16: Synthesis of racemic mc-PAF (16.3), a carbamate analogue of PAF [102].
Figure 17: A) Synthesis of (R)-17.2 and (S)-17.6 starting from (S)-solketal (17.1); B) synthesis of N3-PAF (17...
Figure 18: Modification of the phosphocholine polar head to produce PAF analogues [81].
Figure 19: Racemic PAF analogues 19.3 and 19.5 characterized by the absence of the phosphate group [107].
Figure 20: Synthesis of PIP3-PAF (20.7) [108].
Figure 21: Large-scale synthesis of C18-edelfosine (21.8) [116].
Figure 22: Synthesis of C16-edelfosine (22.10) starting from isopropylidene-ʟ-glyceric acid methyl ester (22.1...
Figure 23: Phosphocholine moiety installation by the use of chlorophosphite 23.2 as key reagent [119].
Figure 24: Synthesis of rac-1-alkyl-2-O-methylglycerol (AMG) [120].
Figure 25: Synthesis of stereocontrolled 1-alkyl-2-O-methyl glycerol 25.9 (AMG) from dimethyl ᴅ-tartrate [81].
Figure 26: A) Racemic synthesis of thioether 26.4 [129,130], B) structure of sulfone analogue 26.5 [129].
Figure 27: Stereocontrolled synthesis of C18-edelfosine thioether analogue 27.8 [118].
Figure 28: Synthesis of thioether 28.4 that include a thiophosphate function [134].
Figure 29: Synthesis of ammonium thioether 29.4 and 29.6 [135].
Figure 30: Synthesis of the N-methylamino analogue of edelfosine 30.6 (BN52211) [138].
Figure 31: Synthesis of 1-desoxy analogues of edelfosine; A) with a saturated alkyl chain; B) synthesis of the...
Figure 32: Stereocontrolled synthesis of edelfosine analogue (S)-32.8 featuring a C18:1 lipid chain [142].
Figure 33: Synthesis of edelfosine analogues with modulation of the lipid chain; A) illustration with the synt...
Figure 34: Synthesis of phospholipid featuring a carbamate function to link the lipid chain to the glycerol un...
Figure 35: Synthesis of sesquiterpene conjugates of phospho glycero ether lipids [148].
Figure 36: Racemic synthesis of methyl-substituted glycerol analogues 36.7 and 36.10: A) synthesis of diether ...
Figure 37: Racemic synthesis of ilmofosine (37.6) [155,156].
Figure 38: A) Stereoselective synthesis of 38.5 via a stereoselective hydroboration reaction; B) synthesis of ...
Figure 39: Racemic synthesis of SRI62-834 (39.6) featuring a spiro-tetrahydrofurane heterocycle in position 2 ...
Figure 40: Racemic synthesis of edelfosine analogue 40.5 featuring an imidazole moiety in sn-2 position [160].
Figure 41: Racemic synthesis of fluorine-functionalized EL: A) Synthesis of 41.6 and B) synthesis of 41.8 [161-163].
Figure 42: A) Synthesis of the β-keto-ester 42.6 that also features a decyl linker between the phosphate and t...
Figure 43: Synthesis of phosphonate-based ether lipids; A) edelfosine phosphonate analogue 43.7 and B) thioeth...
Figure 44: Enantioselective synthesis of phosphonates 44.3 and 44.4 [171].
Figure 45: Racemic synthesis of phosphinate-based ether lipid 45.10 [172].
Figure 46: Racemic synthesis of edelfosine arsonium analogue 46.5 [173].
Figure 47: Synthesis of edelfosine dimethylammonium analogue 47.2 [118].
Figure 48: Synthesis of rac-C18-edelfosine methylammonium analogue 48.4 [176].
Figure 49: A) Synthesis of edelfosine N-methylpyrrolidinium analogue 49.2 or N-methylmorpholinium analogue 49.3...
Figure 50: A) Synthesis of edelfosine’s analogue 50.4 with a PE polar group; B) illustration of a pyridinium d...
Figure 51: A) Synthesis of 51.4 featuring a thiazolium cationic moiety; B) synthesis of thiazolium-based EL 51...
Figure 52: Synthesis of cationic ether lipids 52.3, 52.4 and 52.6 [135,183].
Figure 53: Synthesis of cationic carbamate ether lipid 53.5 [184].
Figure 54: Synthesis of cationic sulfonamide 54.5 [185].
Figure 55: Chemical structure of ONO-6240 (55.1) and SRI-63-119 (55.2).
Figure 56: Synthesis of non-ionic ether lipids 56.2–56.9 [188].
Figure 57: Synthesis of ether lipid conjugated to foscarnet 57.6 [189].
Figure 58: A) Synthesis of ether lipid conjugated to arabinofuranosylcytosine; B) synthesis of AZT conjugated ...
Figure 59: Synthesis of quercetin conjugate to edelfosine [191].
Figure 60: Synthesis of 60.8 (Glc-PAF) [194].
Figure 61: A) Synthesis of amino ether lipid 61.7 functionalized with a rhamnose unit and its amide analogue 6...
Figure 62: A) Synthesis of glucose ether lipid 62.4; B) structure of ether lipid 62.5 possessing a maltose uni...
Figure 63: A) Synthesis of glucuronic methyl ester 63.8; B) structure of cellobiose 63.9 and maltose 63.10 ana...
Figure 64: A) Synthesis of maltosyl glycerolipid 64.7; B) structure of lactose analogue 64.8 prepared followin...
Figure 65: A) Asymmetric synthesis of the aglycone moiety starting from allyl 4-methoxyphenyl ether; B) glycos...
Figure 66: A) Synthesis of ohmline possessing a lactose moiety. B) Structure of other glyco glycero lipids pre...
Figure 67: A) Synthesis of lactose-glycerol ether lipid 67.5; B) analogues possessing a maltose (67.6) or meli...
Figure 68: Synthesis of digalactosyl EL 68.6, A) by using trityl, benzyl and acetyl protecting groups, B) by u...
Figure 69: A) Synthesis of α-ohmline; B) structure of disaccharide ether lipids prepared by using similar meth...
Figure 70: Synthesis of lactose ether lipid 70.3 and its analogue 70.6 featuring a carbamate function as linke...
Figure 71: Synthesis of rhamnopyranoside diether 71.4 [196].
Figure 72: Synthesis of 1-O-hexadecyl-2-O-methyl-3-S-(α-ᴅ-1'-thioglucopyranosyl)-sn-glycerol (72.5) [225].
Figure 73: A) Preparation of lipid intermediate 73.4; B) synthesis of 2-desoxy-C-glycoside 73.10 [226].
Figure 74: Synthesis of galactose-pyridinium salt 74.3 [228].
Figure 75: Synthesis of myo-inositol derivative Ino-C2-PAF (75.10) [230].
Figure 76: A) Synthesis of myo-inositol phosphate building block 76.7; B) synthesis of myo-inositolphosphate d...
Figure 77: A) Synthesis of phosphatidyl-3-desoxy-inositol 77.4; B) synthesis of phosphono-3-desoxyinositol 77.9...
Figure 78: A) Structure of diether phosphatidyl-myo-inositol-3,4-diphosphate 78.1; B) synthesis of phosphatidy...
Figure 79: A) Synthesis of diether-phosphatidyl derivative 79.4 featuring a hydroxymethyl group in place of a ...
Figure 80: Synthesis of Glc-amine-PAF [78].
Figure 81: Synthesis of glucosamine ether lipid 81.4 and its analogues functionalized in position 3 of the ami...
Figure 82: Synthesis of fully deprotected aminoglucoside ether lipid 82.5 [246].
Figure 83: Synthesis of C-aminoglycoside 83.12 using Ramberg–Bäcklund rearrangement as a key step [250].
Figure 84: A) List of the most important glyco lipids and amino glyco lipids included in the study of Arthur a...
Figure 85: Synthesis of mannosamine ether lipid 85.6 [254].
Figure 86: A) Synthesis of glucosamine ether lipids with a non-natural ʟ-glucosamine moiety; B) synthesis of e...
Figure 87: A) Structure of the most efficient anticancer agents 87.1–87.4 featuring a diamino glyco ether lipi...
Figure 88: A) Synthesis of diamino glyco ether lipid 87.4; B) synthesis of bis-glycosylated ether lipid 88.10 [256]....
Figure 89: Synthesis of triamino ether lipid 89.4 [260].
Figure 90: Synthesis of chlorambucil conjugate 90.7 [261].
Figure 91: Three main methods for the preparation of glycerol ether lipid 91.3; A) from solketal and via a tri...
Figure 92: Four different methods for the installation of the phosphocholine polar head group; A) method using...
Figure 93: Illustration of two methods for the installation of saccharides or aminosaccharides; A) O-glycosyla...
Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update
- Anup Biswas
Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72
- after recrystallization. Subsequent ozonolysis of the terminal alkene functionality with a follow-up reduction furnished primary alcohol 134 which was transformed into the azide 135. Reduction of the azide 135 was accompanied by debenzylation, was followed by tosylation of the primary amine and exchange
Graphical Abstract
Scheme 1: First organocatalyzed asymmetric aza-Friedel–Crafts reaction.
Scheme 2: Aza-Friedel–Crafts reaction between indoles and cyclic ketimines.
Scheme 3: Aza-Friedel–Crafts reaction utilizing trifluoromethyldihydrobenzoazepinoindoles as electrophiles.
Scheme 4: Aza-Friedel–Crafts reaction utilizing cyclic N-sulfimines as electrophiles.
Scheme 5: Aza-Friedel–Crafts reaction involving N-unprotected imino ester as electrophile.
Scheme 6: Aza-Friedel–Crafts and lactonization cascade.
Scheme 7: One-pot oxidation and aza-Friedel–Crafts reaction.
Scheme 8: C1 and C2-symmetric phosphoric acids as catalysts.
Scheme 9: Aza-Friedel–Crafts reaction using Nps-iminophosphonates as electrophiles.
Scheme 10: Aza-Friedel–Crafts reaction between indole and α-iminophosphonate.
Scheme 11: [2.2]-Paracyclophane-derived chiral phosphoric acids as catalyst.
Scheme 12: Aza-Friedel–Crafts reaction through ring opening of sulfamidates.
Scheme 13: Isoquinoline-1,3(2H,4H)-dione scaffolds as electrophiles.
Scheme 14: Functionalization of the carbocyclic ring of substituted indoles.
Scheme 15: Aza-Friedel–Crafts reaction between unprotected imines and aza-heterocycles.
Scheme 16: Anilines and α-naphthols as potential nucleophiles.
Scheme 17: Solvent-controlled regioselective aza-Friedel–Crafts reaction.
Scheme 18: Generating central and axial chirality via aza-Friedel–Crafts reaction.
Scheme 19: Reaction between indoles and racemic 2,3-dihydroisoxazol-3-ol derivatives.
Scheme 20: Exploiting 5-aminoisoxazoles as nucleophiles.
Scheme 21: Reaction between unsubstituted indoles and 3-alkynylated 3-hydroxy-1-oxoisoindolines.
Scheme 22: Synthesis of unnatural amino acids bearing an aza-quaternary stereocenter.
Scheme 23: Atroposelective aza-Friedel–Crafts reaction.
Scheme 24: Coupling of 5-aminopyrazole and 3H-indol-3-ones.
Scheme 25: Pyrophosphoric acid-catalyzed aza-Friedel–Crafts reaction on phenols.
Scheme 26: Squaramide-assisted aza-Friedel–Crafts reaction.
Scheme 27: Thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 28: Squaramide-catalyzed reaction between β-naphthols and benzothiazolimines.
Scheme 29: Thiourea-catalyzed reaction between β-naphthol and isatin-derived ketamine.
Scheme 30: Quinine-derived molecule as catalyst.
Scheme 31: Cinchona alkaloid as catalyst.
Scheme 32: aza-Friedel–Crafts reaction by phase transfer catalyst.
Scheme 33: Disulfonamide-catalyzed reaction.
Scheme 34: Heterogenous thiourea-catalyzed aza-Friedel–Crafts reaction.
Scheme 35: Total synthesis of (+)-gracilamine.
Scheme 36: Total synthesis of (−)-fumimycin.
Pyridine C(sp2)–H bond functionalization under transition-metal and rare earth metal catalysis
- Haritha Sindhe,
- Malladi Mounika Reddy,
- Karthikeyan Rajkumar,
- Akshay Kamble,
- Amardeep Singh,
- Anand Kumar and
- Satyasheel Sharma
Beilstein J. Org. Chem. 2023, 19, 820–863, doi:10.3762/bjoc.19.62
- (II)–alkenyl intermediate 88. Then, the intermediate 88 undergoes protio-depalladation and demethylation to yield the Z-isomer 85 (Scheme 17b). In case of N-benzylpyridinium salts 83, first debenzylation occurs to form 2-pyridyl–Cu(I) species 89 in the presence of CuBr which then coordinates to the Pd
Graphical Abstract
Figure 1: Representative examples of bioactive natural products and FDA-approved drugs containing a pyridine ...
Scheme 1: Classical and traditional methods for the synthesis of functionalized pyridines.
Scheme 2: Rare earth metal (Ln)-catalyzed pyridine C–H alkylation.
Scheme 3: Pd-catalyzed C–H alkylation of pyridine N-oxide.
Scheme 4: CuI-catalyzed C–H alkylation of N-iminopyridinium ylides with tosylhydrazones (A) and a plausible r...
Scheme 5: Zirconium complex-catalyzed pyridine C–H alkylation.
Scheme 6: Rare earth metal-catalyzed pyridine C–H alkylation with nonpolar unsaturated substrates.
Scheme 7: Heterobimetallic Rh–Al complex-catalyzed ortho-C–H monoalkylation of pyridines.
Scheme 8: Mono(phosphinoamido)-rare earth complex-catalyzed pyridine C–H alkylation.
Scheme 9: Rhodium-catalyzed pyridine C–H alkylation with acrylates and acrylamides.
Scheme 10: Ni–Al bimetallic system-catalyzed pyridine C–H alkylation.
Scheme 11: Iridium-catalyzed pyridine C–H alkylation.
Scheme 12: para-C(sp2)–H Alkylation of pyridines with alkenes.
Scheme 13: Enantioselective pyridine C–H alkylation.
Scheme 14: Pd-catalyzed C2-olefination of pyridines.
Scheme 15: Ru-catalyzed C-6 (C-2)-propenylation of 2-arylated pyridines.
Scheme 16: C–H addition of allenes to pyridines catalyzed by half-sandwich Sc metal complex.
Scheme 17: Pd-catalyzed stereodivergent synthesis of alkenylated pyridines.
Scheme 18: Pd-catalyzed ligand-promoted selective C3-olefination of pyridines.
Scheme 19: Mono-N-protected amino acids in Pd-catalyzed C3-alkenylation of pyridines.
Scheme 20: Amide-directed and rhodium-catalyzed C3-alkenylation of pyridines.
Scheme 21: Bimetallic Ni–Al-catalyzed para-selective alkenylation of pyridine.
Scheme 22: Arylboronic ester-assisted pyridine direct C–H arylation.
Scheme 23: Pd-catalyzed C–H arylation/benzylation with toluene.
Scheme 24: Pd-catalyzed pyridine C–H arylation with potassium aryl- and heteroaryltrifluoroborates.
Scheme 25: Transient activator strategy in pyridine C–H biarylation.
Scheme 26: Ligand-promoted C3-arylation of pyridine.
Scheme 27: Pd-catalyzed arylation of nicotinic and isonicotinic acids.
Scheme 28: Iron-catalyzed and imine-directed C–H arylation of pyridines.
Scheme 29: Pd–(bipy-6-OH) cooperative system-mediated direct pyridine C3-arylation.
Scheme 30: Pd-catalyzed pyridine N-oxide C–H arylation with heteroarylcarboxylic acids.
Scheme 31: Pd-catalyzed C–H cross-coupling of pyridine N-oxides with five-membered heterocycles.
Scheme 32: Cu-catalyzed dehydrative biaryl coupling of azine(pyridine) N-oxides and oxazoles.
Scheme 33: Rh(III)-catalyzed cross dehydrogenative C3-heteroarylation of pyridines.
Scheme 34: Pd-catalyzed C3-selective arylation of pyridines.
Scheme 35: Rhodium-catalyzed oxidative C–H annulation of pyridines to quinolines.
Scheme 36: Rhodium-catalyzed and NHC-directed C–H annulation of pyridine.
Scheme 37: Ni/NHC-catalyzed regio- and enantioselective C–H cyclization of pyridines.
Scheme 38: Rare earth metal-catalyzed intramolecular C–H cyclization of pyridine to azaindolines.
Scheme 39: Rh-catalyzed alkenylation of bipyridine with terminal silylacetylenes.
Scheme 40: Rollover cyclometallation in Rh-catalyzed pyridine C–H functionalization.
Scheme 41: Rollover pathway in Rh-catalyzed C–H functionalization of N,N,N-tridentate chelating compounds.
Scheme 42: Pd-catalyzed rollover pathway in bipyridine-6-carboxamides C–H arylation.
Scheme 43: Rh-catalyzed C3-acylmethylation of bipyridine-6-carboxamides with sulfoxonium ylides.
Scheme 44: Rh-catalyzed C–H functionalization of bipyridines with alkynes.
Scheme 45: Rh-catalyzed C–H acylmethylation and annulation of bipyridine with sulfoxonium ylides.
Scheme 46: Iridium-catalyzed C4-borylation of pyridines.
Scheme 47: C3-Borylation of pyridines.
Scheme 48: Pd-catalyzed regioselective synthesis of silylated dihydropyridines.
A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups
- Naser-Abdul Yousefi,
- Morten L. Zimmermann and
- Mikael Bols
Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165
- secondary alcohols was prepared and subjected to DIBAL (diisobutylaluminum hydride)-promoted selective debenzylation. Debenzylation proceeded by first removing two dichlorobenzyl groups from the 6A,D positions and then removing one or two benzyl groups from the 3A,D positions. Keywords: aluminum hydrides
- ; cyclodextrin; debenzylation; 2,4-dichlorobenzyl; selective; Introduction α-Cyclodextrin (1) is a cyclic carbohydrate consisting of six α-1,4-linked ᴅ-glucose molecules (Figure 1). It has a donut-like structure with the glucose residues all aligned with the α-side towards the center of the ring and the polar
- linkers, lids or catalytic groups can be installed which is no simple task due to the many similar functionalities in 1 [5][6][7]. A very useful way to access the hydroxy groups in a selective manner is the perbenzylation of 1 and the subsequent selective debenzylation of 2 using DIBAL [8][9][10]. This
Graphical Abstract
Figure 1: Structure of α-cyclodextrins 1–10.
Scheme 1: The reaction of perbenzylated α-cyclodextrin with iBu2AlH.
Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol
- Emine Salamci and
- Ayse Kilic Lafzi
Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163
- )cyclooctane-1,2-diyl dimethanesulfonate. Reaction of the bis(benzyloxy)cyclooctane-1,2-diyl dimethanesulfonate with NaN3 gave 2-azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate. Reduction of the azide group and debenzylation to give an amine provided the new 3-aminocyclooctanetriol. Treatment of the 2
- -azido-3,8-bis(benzyloxy)cyclooctyl methanesulfonate with Zn/NH4Cl and debenzylation resulted in the target aziridinecyclooctanediol. Keywords: aminocyclitols; aminocyclooctanetriol; azides; aziridines; aziridinecyclooctanediol; Introduction Aziridines are the smallest nitrogen-containing heterocycles
Graphical Abstract
Figure 1: Some biologically active aziridine-bearing compounds 1, 2 and aminocyclitol 3.
Scheme 1: Synthesis of dimesylate 8.
Scheme 2: Synthesis of aminocyclooctanetriol 13.
Scheme 3: Synthesis of aziridinecyclooctanediol 16.
Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization
- Sebastien Curpanen,
- Per Reichert,
- Gabriele Lupidi,
- Giovanni Poli,
- Julie Oble and
- Alejandro Perez-Luna
Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131
- debenzylation/cyclization of benzyldimethysilyl-substituted allylic alcohols [32]. To that end, carbinol 4c was treated with TBAF⋅3H2O (1.0 equiv), which resulted in the formation of 16 in 86% yield (along with toluene, Scheme 6). Alike 5-membered cyclic dimethyl(alkenyl)siloxanes, 16 was found to be highly
Graphical Abstract
Scheme 1: C3–Si bond functionalization of biomass-derived 3-silylated furfural platforms.
Scheme 2: Preparation of 3-silylated 2-furyl carbinols.
Scheme 3: C–Si bond functionalization of 2,3-disubstituted furyl carbinols by 1,4-silyl migration.
Scheme 4: Attempts of C3–Si bond functionalization promoted by intramolecular activation via alkoxide.
Scheme 5: Alkoxide-promoted cyclic siloxane formation from 2-[(3-benzyldimethylsilyl)furyl] carbinol 4c.
Scheme 6: TBAF-promoted cyclic siloxane formation from 2-[(3-benzyldimethylsilyl)furyl] carbinol 4c.
Scheme 7: Pd-catalyzed arylation of 2-[(3-benzyldimethylsilyl)furyl] carbinol 4c.
Scheme 8: Cu-catalyzed allylation and methylation of 2-[(3-benzyldimethylsilyl)furyl] carbinols. aCuI⋅PPh3 (1...
Ready access to 7,8-dihydroindolo[2,3-d][1]benzazepine-6(5H)-one scaffold and analogues via early-stage Fischer ring-closure reaction
- Irina Kuznetcova,
- Felix Bacher,
- Daniel Vegh,
- Hsiang-Yu Chuang and
- Vladimir B. Arion
Beilstein J. Org. Chem. 2022, 18, 143–151, doi:10.3762/bjoc.18.15
- [2,3-d][1]benzazepin-6(5H)-one (3a). This procedure delivered analytically pure 3a in 80% yield as also confirmed by SC-XRD (Figure 3). The final step to structure C required removal of the benzyl group. Debenzylation of amines is commonly performed by palladium-catalyzed hydrogenation [40]. However
- the lactam ring of 3a. Gratifyingly, we obtained scaffold C in 71% yield by refluxing 3a with aluminum chloride in benzene (Scheme 6) [43]. For comparison, debenzylation of paullone with sodium in liquid ammonia gave A in 40% yield [23]. In addition, the generality of synthetic pathway (c) (Scheme 1
Graphical Abstract
Figure 1: Paullone related indolobenzazepinone isomers. 7,12-Dihydroindolo[3,2-d][1]benzazepin-6(5H)-one or p...
Scheme 1: Investigated retrosynthetic pathways to scaffold C.
Scheme 2: Attempted synthesis of scaffold C by route (a).
Scheme 3: Attempted synthesis of C by route (b).
Scheme 4: Attempted synthesis of N-benzylated indole-2-acetic acid.
Scheme 5: Attempt to obtain open-chain precursor N-(2-bromophenyl)-2-(1H-indol-2-yl)acetamide.
Scheme 6: Synthesis of scaffold C and analogues by route (c).
Figure 2: ORTEP view of 1a with thermal ellipsoids drawn at the 50% probability level.
Figure 3: ORTEP view of 3a with thermal ellipsoids drawn at the 50% probability level.
Scheme 7: Attempted Ullmann cross-coupling of 23 with o-bromo-nitrobenzene.
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
Graphical Abstract
Figure 1: Representative modified 1,3-oxathiolane nucleoside analogues.
Figure 2: Mechanism of antiviral action of 1,3-oxathiolane nucleosides, 3TC (1) and FTC (2), as chain termina...
Figure 3: Synthetic strategies for the construction of the 1,3-oxathiolane sugar ring.
Scheme 1: Synthesis of 4 from benzoyloxyacetaldehyde (3a) and 2-mercapto-substituted dimethyl acetal 3na.
Scheme 2: Synthesis of 8 from protected glycolic aldehyde 3b and 2-mercaptoacetic acid (3o).
Scheme 3: Synthesis of 20 from ᴅ-mannose (3c).
Scheme 4: Synthesis of 20 from 1,6-thioanhydro-ᴅ-galactose (3d).
Scheme 5: Synthesis of 8 from 2-(tert-butyldiphenylsilyloxy)methyl-5-oxo-1,2-oxathiolane (3m).
Scheme 6: Synthesis of 20a from ʟ-gulose derivative 3f.
Scheme 7: Synthesis of 31 from (+)-thiolactic acid 3p and 2-benzoyloxyacetaldehyde (3a).
Scheme 8: Synthesis of 35a from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g) hydrate.
Scheme 9: Synthetic routes toward 41 through Pummerer reaction from methyl 2-mercaptoacetate (3j) and bromoac...
Scheme 10: Strategy for the synthesis of 2,5-substituted 1,3-oxathiolane 41a using 4-nitrobenzyl glyoxylate an...
Scheme 11: Synthesis of 44 by a resolution method using Mucor miehei lipase.
Scheme 12: Synthesis of 45 from benzoyloxyacetaldehyde (3a) and 2-mercaptoacetaldehyde bis(2-methoxyethyl) ace...
Scheme 13: Synthesis of 46 from 2-mercaptoacetaldehyde bis(2-methoxyethyl) acetal (3nc) and diethyl 3-phosphon...
Scheme 14: Synthesis of 48 from 1,3-dihydroxyacetone dimer 3l.
Scheme 15: Approach toward 52 from protected alkene 3rb and lactic acid derivative 51 developed by Snead et al....
Scheme 16: Recent approach toward 56a developed by Kashinath et al.
Scheme 17: Synthesis of 56a from ʟ-menthyl glyoxylate (3h) hydrate by DKR.
Scheme 18: Possible mechanism with catalytic TEA for rapid interconversion of isomers.
Scheme 19: Synthesis of 35a by a classical resolution method through norephedrine salt 58 formation.
Scheme 20: Synthesis of 63 via [1,2]-Brook rearrangement from silyl glyoxylate 61 and thiol 3nb.
Scheme 21: Combined use of STS and CAL-B as catalysts to synthesize an enantiopure oxathiolane precursor 65.
Scheme 22: Synthesis of 1 and 1a from glycolaldehyde dimer 64 and 1,4-dithiane-2,5-diol (3q) using STS and CAL...
Scheme 23: Synthesis of 68 by using Klebsiella oxytoca.
Scheme 24: Synthesis of 71 and 72 using Trichosporon taibachii lipase and kinetic resolution.
Scheme 25: Synthesis of 1,3-oxathiolan-5-ones 77 and 78 via dynamic covalent kinetic resolution.
Figure 4: Pathway for glycosidic bond formation.
Scheme 26: First synthesis of (±)-BCH-189 (1c) by Belleau et al.
Scheme 27: Enantioselective synthesis of 3TC (1).
Scheme 28: Synthesis of cis-diastereomer 3TC (1) from oxathiolane propionate 44.
Scheme 29: Synthesis of (±)-BCH-189 (1c) via SnCl4-mediated N-glycosylation of 8.
Scheme 30: Synthesis of (+)-BCH-189 (1a) via TMSOTf-mediated N-glycosylation of 20.
Scheme 31: Synthesis of 3TC (1) from oxathiolane precursor 20a.
Scheme 32: Synthesis of 83 via N-glycosylation of 20 with pyrimidine bases.
Scheme 33: Synthesis of 85 via N-glycosylation of 20 with purine bases.
Scheme 34: Synthesis of 86 and 87 via N-glycosylation using TMSOTf and pyrimidines.
Scheme 35: Synthesis of 90 and 91 via N-glycosylation using TMSOTf and purines.
Scheme 36: Synthesis of 3TC (1) via TMSI-mediated N-glycosylation.
Scheme 37: Stereoselective N-glycosylation for the synthesis of 1 by anchimeric assistance of a chiral auxilia...
Scheme 38: Whitehead and co-workers’ approach for the synthesis of 1 via direct N-glycosylation without an act...
Scheme 39: ZrCl4-mediated stereoselective N-glycosylation.
Scheme 40: Plausible reaction mechanism for stereoselective N-glycosylation using ZrCl4.
Scheme 41: Synthesis of enantiomerically pure oxathiolane nucleosides 1 and 2.
Scheme 42: Synthesis of tetrazole analogues of 1,3-oxathiolane nucleosides 97.
Scheme 43: Synthetic approach toward 99 from 1,3-oxathiolane 45 by Camplo et al.
Scheme 44: Synthesis of 100 from oxathiolane phosphonate analogue 46.
Scheme 45: Synthetic approach toward 102 and the corresponding cyclic thianucleoside monophosphate 102a by Cha...
Scheme 46: Synthesis of emtricitabine (2) from 1,4-dithiane-2,5-diol (3q) and glyoxylic acid (3g).
Scheme 47: Synthesis of 1 and 2, respectively, from 56a–d using iodine-mediated N-glycosylation.
Scheme 48: Plausible mechanism for silane- and I2-mediated N-glycosylation.
Scheme 49: Pyridinium triflate-mediated N-glycosylation of 35a.
Scheme 50: Possible pathway for stereoselective N-glycosylation via in situ chelation with a metal ligand.
Scheme 51: Synthesis of novel 1,3-oxathiolane nucleoside 108 from oxathiolane precursor 8 and 3-benzyloxy-2-me...
Scheme 52: Synthesis of 110 using T-705 as a nucleobase and 1,3-oxathiolane derivative 8 via N-glycosylation.
Scheme 53: Synthesis of 1 using an asymmetric leaving group and N-glycosylation with bromine and mesitylene.
Scheme 54: Cytidine deaminase for enzymatic separation of 1c.
Scheme 55: Enzymatic resolution of the monophosphate derivative 116 for the synthesis of (−)-BCH-189 (1) and (...
Scheme 56: Enantioselective resolution by PLE-mediated hydrolysis to obtain FTC (2).
Scheme 57: (+)-Menthyl chloroformate as a resolving agent to separate a racemic mixture 120.
Scheme 58: Separation of racemic mixture 1c by cocrystal 123 formation with (S)-(−)-BINOL.
Progress and challenges in the synthesis of sequence controlled polysaccharides
- Giulio Fittolani,
- Theodore Tyrikos-Ergas,
- Denisa Vargová,
- Manishkumar A. Chaube and
- Martina Delbianco
Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129
Graphical Abstract
Figure 1: Overview of the methods available for the synthesis of polysaccharides. For each method, advantages...
Figure 2: Overview of the classes of polysaccharides discussed in this review. Each section deals with polysa...
Scheme 1: Enzymatic and chemical polymerization approaches provide cellulose oligomers with a non-uniform dis...
Scheme 2: AGA of a collection of cellulose analogues obtained using BBs 6–9. Specifically placed modification...
Figure 3: Chemical structure of the different branches G, X, L, F commonly found in XGs. Names are given foll...
Scheme 3: AGA of XG analogues with defined side chains. The AGA cycle includes coupling (TMSOTf), Fmoc deprot...
Figure 4: Synthetic strategies and issues associated to the formation of the β(1–3) linkage.
Scheme 4: Convergent synthesis of β(1–3)-glucans using a regioselective glycosylation strategy.
Scheme 5: DMF-mediated 1,2-cis glycosylation. A) General mechanism and B) examples of α-glucans prepared usin...
Scheme 6: Synergistic glycosylation strategy employing a nucleophilic modulation strategy (TMSI and Ph3PO) in...
Scheme 7: Different approaches to produce xylans. A) Polymerization techniques including ROP, and B) enzymati...
Scheme 8: A) Synthesis of arabinofuranosyl-decorated xylan oligosaccharides using AGA. Representative compoun...
Scheme 9: Chemoenzymatic synthesis of COS utilizing a lysozyme-catalyzed transglycosylation reaction followed...
Scheme 10: Synthesis of COS using an orthogonal glycosylation strategy based on the use of two different LGs.
Scheme 11: Orthogonal N-PGs permitted the synthesis of COS with different PA.
Scheme 12: AGA of well-defined COS with different PA using two orthogonally protected BBs. The AGA cycle inclu...
Scheme 13: A) AGA of β(1–6)-N-acetylglucosamine hexasaccharide and dodecasaccharide. AGA includes cycles of co...
Figure 5: ‘Double-faced’ chemistry exemplified for ᴅ-Man and ʟ-Rha. Constructing β-Man linkages is considerab...
Figure 6: Implementation of a capping step after each glycosylation cycle for the AGA of a 50mer oligomannosi...
Scheme 14: AGA enabled the synthesis of a linear α(1–6)-mannoside 100mer 93 within 188 h and with an average s...
Scheme 15: The 151mer branched polymannoside was synthesized by a [30 + 30 + 30 + 30 + 31] fragment coupling. ...
Figure 7: PG stereocontrol strategy to obtain β-mannosides. A) The mechanism of the β-mannosylation reaction ...
Scheme 16: A) Mechanism of 1,2-cis stereoselective glycosylation using ManA donors. Once the ManA donor is act...
Figure 8: A) The preferred 4H3 conformation of the gulosyl oxocarbenium ion favors the attack of the alcohol ...
Scheme 17: AGA of type I rhamnans up to 16mer using disaccharide BB 115 and CNPiv PG. The AGA cycle includes c...
Figure 9: Key BBs for the synthesis of the O-antigen of Bacteroides vulgatus up to a 128mer (A) and the CPS o...
Figure 10: Examples of type I and type II galactans synthesized to date.
Figure 11: A) The DTBS PG stabilizes the 3H4 conformation of the Gal oxocarbenium ion favoring the attack of t...
Figure 12: Homogalacturonan oligosaccharides synthesized to date. Access to different patterns of methyl-ester...
Figure 13: GlfT2 from Mycobacterium tuberculosis catalyzes the sequential addition of UPD-Galf donor to a grow...
Figure 14: The poor reactivity of acceptor 137 hindered a stepwise synthesis of the linear galactan backbone a...
Scheme 18: AGA of a linear β(1–5) and β(1–6)-linked galactan 20mer. The AGA cycle includes coupling (NIS/TfOH)...
Figure 15: The 92mer arabinogalactan was synthesized using a [31 + 31 + 30] fragment coupling between a 31mer ...
Scheme 19: Synthesis of the branched arabinofuranose fragment using a six component one-pot synthesis. i) TTBP...
Figure 16: A) Chemical structure and SNFG of the representative disaccharide units forming the GAG backbones, ...
Figure 17: Synthetic challenges associated to the H/HS synthesis.
Scheme 20: Degradation of natural heparin and heparosan generated valuable disaccharides 150 and 151 that can ...
Scheme 21: A) The one-step conversion of cyanohydrin 156 to ʟ-iduronamide 157 represent the key step for the s...
Scheme 22: A) Chemoenzymatic synthesis of heparin structures, using different types of UDP activated natural a...
Scheme 23: Synthesis of the longest synthetic CS chain 181 (24mer) using donor 179 and acceptor 180 in an iter...
Scheme 24: AGA of a collection of HA with different lengths. The AGA cycle includes coupling (TfOH) and Lev de...
Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings
- Ivan P. Mosiagin,
- Olesya A. Tomashenko,
- Dar’ya V. Spiridonova,
- Mikhail S. Novikov,
- Sergey P. Tunik and
- Alexander F. Khlebnikov
Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105
- could be performed only with AlCl3 under harsh conditions and, therefore, cannot be used for the preparation of compounds with acid-sensitive substituents. In addition, the debenzylation of 1-benzyl-3-arylpyrido[2,1-a]pyrrolo[3,2-c]isoquinolines A was found to accompany by isomerization to 2-aryl
Graphical Abstract
Scheme 1: Retrosynthetic analysis of heterocycles A and B.
Figure 1: Molecular structure of compound 3a, displacement parameters are drawn at 50%.
Scheme 2: Free-radical cyclization of N-protected and N-unprotected pyrroles 1a and 2.
Scheme 3: Synthesis of 2H-pyrido[2,1-a]pyrrolo[3,4-c]isoquinolin-4-ium bromide 8.
Scheme 4: Free-radical cyclization of dihalogeno-substituted salts 9 and 12.
Figure 2: Molecular structure of compound 13, displacement parameters are drawn at 50% probability level.
Scheme 5: N-alkylation of the base 6a.
Figure 3: Molecular structure of compound 17a, displacement parameters are drawn at 50% probability level.
Scheme 6: Isomerization of compounds 17a and 18a.
Scheme 7: N-Alkylation of compounds 18a and 19.
Double-headed nucleosides: Synthesis and applications
- Vineet Verma,
- Jyotirmoy Maity,
- Vipin K. Maikhuri,
- Ritika Sharma,
- Himal K. Ganguly and
- Ashok K. Prasad
Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98
- ] synthesized the double-headed nucleoside (1S,3R,4R,6R,7S)-7-hydroxy-1-(hydroxymethyl)-3-(thymin-1-yl)-6-(4-(thymin-1-ylmethyl)-1,2,3-triazol-1-yl)methyl-2,5-dioxabicyclo[2.2.1]heptane (127). The CuAAc reaction of nucleoside azide 126 with propargylated thymine followed by Pd-catalyzed debenzylation under
Graphical Abstract
Figure 1: Double-headed nucleosides. B1 and B2 = nucleobases or heterocyclic/carbocyclic moieties; L = linker....
Scheme 1: Synthesis of 2′-(pyrimidin-1-yl)methyl- or 2′-(purin-9-yl)methyl-substituted double-headed nucleosi...
Scheme 2: Synthesis of double-headed nucleoside 7 having two cytosine moieties.
Scheme 3: Synthesis of double-headed nucleoside 2′-deoxy-2′-C-(2-(thymine-1-yl)ethyl)-uridine (11).
Scheme 4: Double-headed nucleosides 14 and 15 obtained by click reaction.
Scheme 5: Synthesis of the double-headed nucleoside 19.
Scheme 6: Synthesis of the double-headed nucleosides 24 and 25.
Scheme 7: Synthesis of double-headed nucleosides 28 and 29.
Scheme 8: Synthesis of double-headed nucleoside 33.
Scheme 9: Synthesis of double-headed nucleoside 37.
Scheme 10: Synthesis of the double-headed nucleoside 1-(5′-O-(4,4′-dimethoxytrityl)-2′-C-((4-(pyren-1-yl)-1,2,...
Scheme 11: Synthesis of triazole-containing double-headed ribonucleosides 46a–c and 50a–e.
Scheme 12: Synthesis of double-headed nucleosides 54a–g.
Scheme 13: Synthesis of double-headed nucleosides 59 and 60.
Scheme 14: Synthesis of the double-headed nucleosides 63 and 64.
Scheme 15: Synthesis of double-headed nucleosides 66a–c.
Scheme 16: Synthesis of benzoxazole-containing double-headed nucleosides 69 and 71 from 5′-amino-5′-deoxynucle...
Scheme 17: Synthesis of 4′-C-((N6-benzoyladenin-9-yl)methyl)thymidine (75) and 4′-C-((thymin-1-yl)methyl)thymi...
Scheme 18: Synthesis of double-headed nucleosides 5′-(adenine-9-yl)-5′-deoxythymidine (79) and 5′-(adenine-9-y...
Scheme 19: Synthesis of double-headed nucleosides 85–87 via reversed nucleosides methodology.
Scheme 20: Double-headed nucleosides 91 and 92 derived from ω-terminal-acetylenic sugar derivatives 90a,b.
Scheme 21: Synthesis of double-headed nucleosides 96a–g.
Scheme 22: Synthesis of double-headed nucleosides 100 and 103.
Scheme 23: Double-headed nucleosides 104 and 105 with a triazole motif.
Scheme 24: Synthesis of the double-headed nucleosides 107 and 108.
Scheme 25: Synthesis of double-headed nucleoside 110 with additional nucleobase in 5′-(S)-C-position joined th...
Scheme 26: Synthesis of double-headed nucleosides 111–113 with additional nucleobases in the 5′-(S)-C-position...
Scheme 27: Synthesis of double-headed nucleoside 114 by click reaction.
Scheme 28: Synthesis of double-headed nucleosides 118 with an additional nucleobase at the 5′-(S)-C-position.
Scheme 29: Synthesis of bicyclic double-headed nucleoside 122.
Scheme 30: Synthesis of double-headed nucleosides 125a–c derived from 2′-amino-LNA.
Scheme 31: Double-headed nucleoside 127 obtained by click reaction.
Scheme 32: Synthesis of double-headed nucleoside 130.
Scheme 33: Double-headed nucleosides 132a–d and 134a–d synthesized by Sonogashira cross coupling reaction.
Scheme 34: Synthesis of double-headed nucleosides 137 and 138 via Suzuki coupling.
Scheme 35: Synthesis of double-headed nucleosides 140 and 141 via Sonogashira cross coupling reaction.
Scheme 36: Synthesis of double-headed nucleoside 143.
Scheme 37: Synthesis of the double-headed nucleoside 146.
Scheme 38: Synthesis of 5-C-alkynyl-functionalized double-headed nucleosides 151a–d.
Scheme 39: Synthesis of 5-C-triazolyl-functionalized double-headed nucleosides 154a, b.
Scheme 40: Synthesis of double-headed nucleosides 157a–c.
Scheme 41: Synthesis of double-headed nucleoside 159, phosphoramidite 160 and the corresponding nucleotide mon...
Scheme 42: Synthesis of double-headed nucleoside 163, phosphoramidite 164 and the corresponding nucleotide mon...
Scheme 43: Synthesis of double-headed nucleoside 167, phosphoramidite 168, and the corresponding nucleotide mo...
Scheme 44: Synthesis of double-headed nucleoside 171, phosphoramidite 172, and the corresponding nucleotide mo...
Scheme 45: Synthesis of double-headed nucleoside 175, phosphoramidite 176, and the corresponding nucleotide mo...
Scheme 46: Synthesis of double-headed nucleoside 178.
Scheme 47: Synthesis of the double-headed nucleosides 181 and 183.
Scheme 48: Alternative synthesis of the double-headed nucleoside 183.
Scheme 49: Synthesis of double-headed nucleoside 188 through thermal [2 + 3] sydnone–alkyne cycloaddition reac...
Scheme 50: Synthesis of the double-headed nucleosides 190 and 191.
Scheme 51: Synthesis of 1-((5S)-2,3,4-tri-O-acetyl-5-(2,6-dichloropurin-9-yl)-β-ᴅ-xylopyranosyl)uracil (195).
Scheme 52: Synthesis of hexopyranosyl double-headed pyrimidine homonucleosides 200a–c.
Figure 2: 3′-C-Ethynyl-β-ᴅ-allopyranonucleoside derivatives 201a–f.
Scheme 53: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 203–207.
Scheme 54: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleosides 208 and 209.
Scheme 55: Synthesis of 3′-C-(1,4-disubstituted-1,2,3-triazolyl)-double-headed pyranonucleoside 210.
Scheme 56: Synthesis of double-headed acyclic nucleosides (2S,3R)-1,4-bis(thymine-1-yl)butane-2,3-diol (213a) ...
Scheme 57: Synthesis of double-headed acyclic nucleosides (2R,3S)-1,4-bis(thymine-1-yl)butane-2,3-diol (213c) ...
Scheme 58: Synthesis of double-headed acetylated 1,3,4-oxadiazino[6,5-b]indolium-substituted C-nucleosides 218b...
Scheme 59: Synthesis of double-headed acyclic nucleoside 222.
Scheme 60: Synthesis of functionalized 1,2-bis(1,2,4-triazol-3-yl)ethane-1,2-diols 223a–f.
Scheme 61: Synthesis of acyclic double-headed 1,2,4-triazino[5,6-b]indole C-nucleosides 226–231.
Scheme 62: Synthesis of double-headed 1,3,4-thiadiazoline, 1,3,4-oxadiazoline, and 1,2,4-triazoline acyclo C-n...
Scheme 63: Synthesis of double-headed acyclo C-nucleosides 240–242.
Scheme 64: Synthesis of double-headed acyclo C-nucleoside 246.
Scheme 65: Synthesis of acyclo double-headed nucleoside 250.
Scheme 66: Synthesis of acyclo double-headed nucleoside 253.
Scheme 67: Synthesis of acyclo double-headed nucleosides 259a–d.
Scheme 68: Synthesis of acyclo double-headed nucleoside 261.
Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides
- Vojtěch Hamala,
- Lucie Červenková Šťastná,
- Martin Kurfiřt,
- Petra Cuřínová,
- Martin Dračínský and
- Jindřich Karban
Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85
- -catalyzed hydrogenolysis in ethanol/acetic anhydride appeared to be a logical deprotection step [26], the desired fluoro sugars were contaminated with varying quantities of unidentified byproducts. However, clean debenzylation was achieved by first converting the azide to an acetamide on reaction with
- degree upon reaction with AcSH in pyridine and traces of O1 acetates were removed by chromatography or recrystallization. Palladium-catalyzed hydrogenolytic debenzylation of 49–58 then yielded the target fluoro analogs 61–70. To complete the series of fluorinated analogs for the purpose of comparing
- conversion and debenzylation. The values [Hz] of selected coupling constants. Boldfaced values illustrate the trends discussed in the text. Supporting Information Supporting Information File 89: Experimental procedures and spectral data. Supporting Information File 90: Copies of 1H, 13C, 19F, and 2D NMR
Graphical Abstract
Scheme 1: Retrosynthetic analysis of the target fluoro analogs.
Scheme 2: Conversion of 1,6-anhydro derivatives into thioglycosides, and a possible mechanism for the formati...
Scheme 3: Deoxyfluorination and O-benzylation of thioglycosides and thioaglycone migration.
Scheme 4: Thioglycoside hydrolysis.
Scheme 5: Synthesis of the target compounds by azide/acetamide conversion and debenzylation.
Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles
- Lívia Dikošová,
- Júlia Laceková,
- Ondrej Záborský and
- Róbert Fischer
Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112
- (Scheme 4). According to the literature, the N-debenzylation by a Pd-catalyzed hydrogenolysis in methanol with formic acid as the hydrogen source [37][38] should allow the access to N-deprotected isoxazolidines. Unfortunately, all attempts to remove the benzyl group directly from the model isoxazolidine
- 8b resulted only in a reductive cleavage of the N–O bond. A successful debenzylation was achieved in a two-step procedure using 2,2,2-trichloroethyl chloroformate (TrocCl). However, the protection of the hydroxy group was required first (for the reaction of 8b with benzoyl chloride, see Supporting
- was successfully used for the inversion of the C-3/4-trans relative configuration of the isoxazolidine ring. The bulkier ʟ-selectride showed an excellent selectivity toward the C-3/4-cis isomer compared to lithium borohydride. The final N-debenzylation by a two-step procedure involving a basic
Graphical Abstract
Figure 1: 3-Substituted isoxazolidin-4-ols resembling 3-hydroxypyrrolidines.
Scheme 1: Synthetic approach towards isoxazolidin-4-ols via the regioselective reductive cleavage of the C5–O...
Scheme 2: Hydroboration-oxidation of 4,5-unsubstituted 2,3-dihydroisoxazoles.
Figure 2: Selected NOE enhancements observed in the isoxazolidin-4-ol trans-8a. The arrows show the NOESY cor...
Scheme 3: Dess-Martin oxidation of isoxazolidin-4-ols to ketones.
Scheme 4: Inversion of the relative configuration of the isoxazolidine ring.
Figure 3: Selected NOE enhancements observed in the isoxazolidin-4-ol cis-10a. The arrows show the NOESY corr...
Scheme 5: N-debenzylation via N-Troc-protected isoxazolidines.
Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates
- Marcin Kaźmierczak and
- Henryk Koroniak
Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69
- into the salts 14 was applied. The salts 14 could be then crystallized and subjected to X-ray studies. A standard N−debenzylation protocol was employed to remove the benzyl protecting group. The hydrogenolysis reaction was catalyzed by palladium on carbon (Pd/C), and was carried out in trifluoroethanol
Graphical Abstract
Figure 1: Chemical structure of PyFluor, PBSF and SulfoxFluor.
Scheme 1: Synthesis of 5.
Figure 2: Chemical structure bases.
Scheme 2: Synthesis of 11.
Scheme 3: Synthesis of 13 and 14.
Figure 3: Molecular structure of compound (1R,2S)-14c (ORTEP image).
Scheme 4: Synthesis of 15. aConditions are given in the Experimental section.
Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules
- Valerian Dragutan,
- Ileana Dragutan,
- Albert Demonceau and
- Lionel Delaude
Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68
- in the pyrrolidine ring catalyzed by RhCl3·H2O, followed by debenzylation, amidation, and aminal generation using the Stille protocol [77]. (–)‐Clavukerin A and related sesquiterpenes Applying original organocatalytic/metal-catalyzed tactics, Metz et al. [78] reported a tandem dienyne RCM for the
Graphical Abstract
Scheme 1: Intramolecular (A) and intermolecular (B) enyne metathesis reactions.
Scheme 2: Ene–yne and yne–ene mechanisms for intramolecular enyne metathesis reactions.
Scheme 3: Metallacarbene mechanism in intermolecular enyne metathesis.
Scheme 4: The Oguri strategy for accessing artemisinin analogs 1a–c through enyne metathesis.
Scheme 5: Access to the tetracyclic core of nanolobatolide (2) via tandem enyne metathesis followed by an Eu(...
Scheme 6: Synthesis of (−)-amphidinolide E (3) using an intermolecular enyne metathesis as the key step.
Scheme 7: Synthesis of amphidinolide K (4) by an enyne metathesis route.
Scheme 8: Trost synthesis of des-epoxy-amphidinolide N (5) [72].
Scheme 9: Enyne metathesis between the propargylic derivative and the allylic alcohol in the synthesis of the...
Scheme 10: Synthetic route to amphidinolide N (6a).
Scheme 11: Synthesis of the stereoisomeric precursors of amphidinolide V (7a and 7b) through alkyne ring-closi...
Scheme 12: Synthesis of the anthramycin precursor 8 from ʟ-methionine by a tandem enyne metathesis–cross metat...
Scheme 13: Synthesis of (−)‐clavukerin A (9) and (−)‐isoclavukerin A (10) by an enyne metathesis route startin...
Scheme 14: Synthesis of (−)-isoguaiene (11) through an enyne metathesis as the key step.
Scheme 15: Synthesis of erogorgiaene (12) by a tandem enyne metathesis/cross metathesis sequence using the sec...
Scheme 16: Synthesis of (−)-galanthamine (13) from isovanilin by an enyne metathesis.
Scheme 17: Application of enyne metathesis for the synthesis of kempene diterpenes 14a–c.
Scheme 18: Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis.
Scheme 19: Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis.
Scheme 20: Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions.
Scheme 21: Total synthesis of (−)-flueggine A (18) and (+)-virosaine B (19) from Weinreb amide by enyne metath...
Scheme 22: Access to virgidivarine (20) and virgiboidine (21) by an enyne metathesis route.
Scheme 23: Enyne metathesis approach to (−)-zenkequinone B (22).
Scheme 24: Access to C-aryl glycoside 23 by an intermolecular enyne metathesis/Diels–Alder cycloaddition.
Scheme 25: Synthesis of spiro-C-aryl glycoside 24 by a tandem intramolecular enyne metathesis/Diels–Alder reac...
Scheme 26: Pathways to (−)-exiguolide (25) by Trost’s Ru-catalyzed enyne cross-coupling and cross-metathesis [94].
Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis
- David C. B. Siebert,
- Roman Sommer,
- Domen Pogorevc,
- Michael Hoffmann,
- Silke C. Wenzel,
- Rolf Müller and
- Alexander Titz
Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286
- -ᴅ-Ala (16) was coupled to O-benzylserine ethyl ester 37 to give dipeptide 38, hydrogenolytic debenzylation gave the substrate 39 for the copper(I)-mediated elimination of the carbodiimide formed in situ using EDC, and then yielded the dipeptide Boc-ᴅ-Ala-Dha ester 40 in good yields. Lithium
Graphical Abstract
Figure 1: Chemical structures of naturally occurring argyrins with potent antipseudomonal activity.
Figure 2: The biosynthetic pathway for argyrin production in Cystobacter sp. SBCb004 (Arg1, radical SAM-depen...
Figure 3: Designed mutasynthons 9–14 for argyrin biosynthesis. Peptides are based on three amino acids and ad...
Scheme 1: Synthesis of tripeptide thioesters. Reagents and conditions: (a) SOCl2, EtOH, 78 °C; (b) IBCF, NMM,...
Scheme 2: Improved synthesis of the tripeptide thioester 14. Reagents and conditions: (a) SOCl2, EtOH, 78 °C;...
Figure 4: Analysis of mutasynthon 14 obtained via the convergent synthetic route by HPLC on a HILIC stationar...
N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds
- Iwona E. Głowacka,
- Aleksandra Trocha,
- Andrzej E. Wróblewski and
- Dorota G. Piotrowska
Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168
- selective desilylation and N-debenzylation with simultaneous N-Boc protection and served as a key intermediate for installation of a dimethylhexylene fragment in Julia–Kocienski olefination [56]. Pyrrolidine alkaloids (−)-hygrine ((S)-61) and (−)-hygroline ((2S,2'S)-62) were isolated from many natural
- morpholine first required the reaction with iodotrimethylsilane and furnished diamino alcohol 82 which after N-debenzylation and acylation gave (1R,2R)-81. In a similar way other GCS inhibitors, e.g., ᴅ-threo-P4 (1R,2R)-83a and ᴅ-threo-4'-hydroxy-P4 (1R,2R)-83b (Scheme 20) were obtained and examined as
- group was acquired as shown earlier to provide (2S,3R)-92a and (2S,3R)-92b as N-Boc derivatives after N-debenzylation. Analogues (2S,3R)-89a (DS-SG-44) and (2S,3R)-89b (DS-SG-45) were formed after a regioselective phosphorylation and final treatment with bromotrimethylsilane. DS-SG-44 emerged as an
Graphical Abstract
Figure 1: Examples of three-carbon chirons.
Figure 2: Structures of derivatives of N-(1-phenylethyl)aziridine-2-carboxylic acid 5–8.
Figure 3: Synthetic equivalency of aziridine aldehydes 6.
Scheme 1: Synthesis of N-(1-phenylethyl)aziridine-2-carboxylates 5. Reagents and conditions: a) TEA, toluene,...
Scheme 2: Absolute configuration at C2 in (2S,1'S)-5a. Reagents and conditions: a) 20% HClO4, 80 °C, 30 h the...
Scheme 3: Major synthetic strategies for a 2-ketoaziridine scaffold [R* = (R)- or (S)-1-phenylethyl; R′ = Alk...
Scheme 4: Synthesis of cyanide (2S,1'S)-13. Reagents and conditions: a) NH3, EtOH/H2O, rt, 72 h; b) Ph3P, CCl4...
Scheme 5: Synthesis of key intermediates (R)-16 and (R)-17 for (R,R)-formoterol (14) and (R)-tamsulosin (15)....
Scheme 6: Synthesis of mitotic kinesin inhibitors (2R/S,1'R)-23. Reagents and conditions: a) H2, Pd(OH)2, EtO...
Scheme 7: Synthesis of (R)-mexiletine ((R)-24). Reagents and conditions: a) TsCl, TEA, DMAP, CH2Cl2, rt, 1 h;...
Scheme 8: Synthesis of (−)-cathinone ((S)-27). Reagents and conditions: a) PhMgBr, ether, 0 °C; b) H2, 10% Pd...
Scheme 9: Synthesis of N-Boc-norpseudoephedrine ((1S,2S)-(+)-29) and N-Boc-norephedrine ((1R,2S)-29). Reagent...
Scheme 10: Synthesis of (−)-ephedrine ((1R,2S)-31). Reagents and conditions: a) TfOMe, MeCN then NaBH3CN, rt; ...
Scheme 11: Synthesis of xestoaminol C ((2S,3R)-35), 3-epi-xestoaminol C ((2S,3S)-35) and N-Boc-spisulosine ((2S...
Scheme 12: Synthesis of ʟ-tryptophanol ((S)-41). Reagents and conditions: a) CDI, MeCN, rt, 1 h then TMSI, MeC...
Scheme 13: Synthesis of ʟ-homophenylalaninol ((S)-42). Reagents and conditions: a) NaH, THF, 0 °C to −78 °C, 1...
Scheme 14: Synthesis of ᴅ-homo(4-octylphenyl)alaninol ((R)-47) and a sphingolipid analogue (R)-48. Reagents an...
Scheme 15: Synthesis of florfenicol ((1R,2S)-49). Reagents and conditions: a) (S)-1-phenylethylamine, TEA, MeO...
Scheme 16: Synthesis of natural tyroscherin ((2S,3R,6E,8R,10R)-55). Reagents and conditions: a) I(CH2)3OTIPS, t...
Scheme 17: Syntheses of (−)-hygrine (S)-61, (−)-hygroline (2S,2'S)-62 and (−)-pseudohygroline (2S,2'R)-62. Rea...
Scheme 18: Synthesis of pyrrolidine (3S,3'R)-68, a fragment of the fluoroquinolone antibiotic PF-00951966. Rea...
Scheme 19: Synthesis of sphingolipid analogues (R)-76. Reagents and conditions: a) BnBr, Mg, THF, reflux, 6 h;...
Scheme 20: Synthesis of ᴅ-threo-PDMP (1R,2R)-81. Reagents and conditions: a) TMSCl, NaI, MeCN, rt, 1 h 50 min,...
Scheme 21: Synthesis of the sphingolipid analogue SG-14 (2S,3S)-84. Reagents and conditions: a) LiAlH4, THF, 0...
Scheme 22: Synthesis of the sphingolipid analogue SG-12 (2S,3R)-88. Reagents and conditions: a) 1-(bromomethyl...
Scheme 23: Synthesis of sphingosine-1-phosphate analogues DS-SG-44 and DS-SG-45 (2S,3R)-89a and (2S,3R)-89a. R...
Scheme 24: Synthesis of N-Boc-safingol ((2S,3S)-95) and N-Boc-ᴅ-erythro-sphinganine ((2S,3R)-95). Reagents and...
Scheme 25: Synthesis of ceramide analogues (2S,3R)-96. Reagents and conditions: a) NaBH4, ZnCl2, MeOH, −78 °C,...
Scheme 26: Synthesis of orthogonally protected serinols, (S)-101 and (R)-102. Reagents and conditions: a) BnBr...
Scheme 27: Synthesis of N-acetyl-3-phenylserinol ((1R,2R)-105). Reagents and conditions: a) AcOH, CH2Cl2, refl...
Scheme 28: Synthesis of (S)-linezolid (S)-107. Reagents and conditions: a) LiAlH4, THF, 0 °C to reflux; b) Boc2...
Scheme 29: Synthesis of (2S,3S,4R)-2-aminooctadecane-1,3,4-triol (ᴅ-ribo-phytosphingosine) (2S,3S,4R)-110. Rea...
Scheme 30: Syntheses of ᴅ-phenylalanine (R)-116. Reagents and conditions: a) AcOH, CH2Cl2, reflux, 4 h; b) MsC...
Scheme 31: Synthesis of N-Boc-ᴅ-3,3-diphenylalanine ((R)-122). Reagents and conditions: a) PhMgBr, THF, −78 °C...
Scheme 32: Synthesis of ethyl N,N’-di-Boc-ʟ-2,3-diaminopropanoate ((S)-125). Reagents and conditions: a) NaN3,...
Scheme 33: Synthesis of the bicyclic amino acid (S)-(+)-127. Reagents and conditions: a) BF3·OEt2, THF, 60 °C,...
Scheme 34: Synthesis of lacosamide, (R)-2-acetamido-N-benzyl-3-methoxypropanamide (R)-130. Reagents and condit...
Scheme 35: Synthesis of N-Boc-norfuranomycin ((2S,2'R)-133). Reagents and conditions: a) H2C=CHCH2I, NaH, THF,...
Scheme 36: Synthesis of MeBmt (2S,3R,4R,6E)-139. Reagents and conditions: a) diisopropyl (S,S)-tartrate (E)-cr...
Scheme 37: Synthesis of (+)-polyoxamic acid (2S,3S,4S)-144. Reagents and conditions: a) AD-mix-α, MeSO2NH2, t-...
Scheme 38: Synthesis of the protected 3-hydroxy-ʟ-glutamic acid (2S,3R)-148. Reagents and conditions: a) LiHMD...
Scheme 39: Synthesis of (+)-isoserine (R)-152. Reagents and conditions: a) AcCl, MeCN, rt, 0.5 h then Na2CO3, ...
Scheme 40: Synthesis of (3R,4S)-N3-Boc-3,4-diaminopentanoic acid (3R,4S)-155. Reagents and conditions: a) Ph3P...
Scheme 41: Synthesis of methyl (2S,3S,4S)-4-(dimethylamino)-2,3-dihydroxy-5-methoxypentanoate (2S,3S,4S)-159. ...
Scheme 42: Syntheses of methyl (3S,4S) 4,5-di-N-Boc-amino-3-hydroxypentanoate ((3S,4S)-164), methyl (3S,4S)-4-N...
Scheme 43: Syntheses of (3R,5S)-5-(aminomethyl)-3-(4-methoxyphenyl)dihydrofuran-2(3H)-one ((3R,5S)-168). Reage...
Scheme 44: Syntheses of a series of imidazolin-2-one dipeptides 175–177 (for R' and R'' see text). Reagents an...
Scheme 45: Syntheses of (2S,3S)-N-Boc-3-hydroxy-2-hydroxymethylpyrrolidine ((2S,3S)-179). Reagents and conditi...
Scheme 46: Syntheses of enantiomers of 1,4-dideoxy-1,4-imino-ʟ- and -ᴅ-lyxitols (2S,3R,4S)-182 and (2R,3S,4R)-...
Scheme 47: Synthesis of 1,4-dideoxy-1,4-imino-ʟ-ribitol (2S,3S,4R)-182. Reagents and conditions: a) AcOH, CH2Cl...
Scheme 48: Syntheses of 1,4-dideoxy-1,4-imino-ᴅ-arabinitol (2R,3R,4R)-182 and 1,4-dideoxy-1,4-imino-ᴅ-xylitol ...
Scheme 49: Syntheses of natural 2,5-imino-2,5,6-trideoxy-ʟ-gulo-heptitol ((2S,3R,4R,5R)-184) and its C4 epimer...
Scheme 50: Syntheses of (−)-dihydropinidine ((2S,6R)-187a) (R = C3H7) and (2S,6R)-isosolenopsins (2S,6R)-187b ...
Scheme 51: Syntheses of (+)-deoxocassine ((2S,3S,6R)-190a, R = C12H25) and (+)-spectaline ((2S,3S,6R)-190b, R ...
Scheme 52: Synthesis of (−)-microgrewiapine A ((2S,3R,6S)-194a) and (+)-microcosamine A ((2S,3R,6S)-194b). Rea...
Scheme 53: Syntheses of ʟ-1-deoxynojirimycin ((2S,3S,4S,5R)-200), ʟ-1-deoxymannojirimycin ((2S,3S,4S,5S)-200) ...
Scheme 54: Syntheses of 1-deoxy-ᴅ-galacto-homonojirimycin (2R,3S,4R,5S)-211. Reagents and conditions: a) MeONH...
Scheme 55: Syntheses of 7a-epi-hyacinthacine A1 (1S,2R,3R,7aS)-220. Reagents and conditions: a) TfOTBDMS, 2,6-...
Scheme 56: Syntheses of 8-deoxyhyacinthacine A1 ((1S,2R,3R,7aR)-221). Reagents and conditions: a) H2, Pd/C, PT...
Scheme 57: Syntheses of (+)-lentiginosine ((1S,2S,8aS)-227). Reagents and conditions: a) (EtO)2P(O)CH2COOEt, L...
Scheme 58: Syntheses of 8-epi-swainsonine (1S,2R,8S,8aR)-231. Reagents and conditions: a) Ph3P=CHCOOMe, MeOH, ...
Scheme 59: Synthesis of a protected vinylpiperidine (2S,3R)-237, a key intermediate in the synthesis of (−)-sw...
Scheme 60: Synthesis of a modified carbapenem 245. Reagents and conditions: a) AcOEt, LiHMDS, THF, −78 °C, 1.5...
Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors
- Alexander Dahlqvist,
- Axel Furevi,
- Niklas Warlin,
- Hakon Leffler and
- Ulf J. Nilsson
Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102
- substituents other than fluorine could be prepared, as they were dehalogenated during the final debenzylation. Galectin binding Galectin-1, -3, -4C (C-terminal CRD), -4N (N-terminal CRD), -7, -8C, -8N, -9C, and -9N affinities for (aryltriazolyl)methyl galactopyranosyls 1a–n were determined in a competitive
Graphical Abstract
Scheme 1: Diastereoselective hydroboration of glycopyranosyl exomethylene enol ethers 2, 4, and 6: a) BH3-DMS...
Scheme 2: Synthesis of (aryltriazolyl)methylene galactopyranosides 1a–n. Conditions: a) 3, MsCl, pyridine, 0 ...
Figure 1: Galectin-1 in complex with 1b derived by energy-minimizing a representative snapshot from a 200 ns ...
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
- the amine using LiAlH4 with concomitant debenzoylation, followed by the acylation of the amine with lauric acid to afford 9a, and finally, ii) reductive cleavage by hydrogenolysis using Pd–C/H2 leading to debenzylation (Scheme 3). However, during hydrogenolysis, the elimination of the -OBn group led
- to product 9b, which was undesirable. A similar elimination was earlier observed by Sharf et al. during hydrogenolysis of dibenzyl ether [55]. To avoid this, an oxidative debenzylation of 9a using DDQ/CH2Cl2–H2O was carried out. However, this led to a very poor yield of the target compound 2 (Scheme
- 3). Hence, we decided to debenzylate compound 9 prior to its reduction to the amine and subsequent acylation. Towards this (Scheme 4), oxidative debenzylation of 9 using DDQ yielded 10 in 84% yield. Treatment of 10 with LiAlH4 led to the reduction of the azide group to amine along with
Graphical Abstract
Figure 1: Structure of most active HPA-12 isomers, originally proposed (1) and revised (2).
Scheme 1: Lipase-catalyzed trans-acylation of (±)-4 and subsequent Mitsunobu inversion. Conditions: (i) Zn/TH...
Scheme 2: Synthesis of azide 9 from (S)-4. Conditions: (i) NaH/Bu4NI/BnBr/THF/25 °C/4 h; (ii) AD-mix-β/t-BuOH...
Scheme 3: Attempted synthesis of 2 from 9. Conditions: (i) (a) LiAlH4 (1 M in THF)/THF/25 °C/3 h, (b) DCC/DMA...
Scheme 4: Actual synthesis of 2 from 9. Conditions: (i) DDQ/CH2Cl2–H2O 4:1/3 h; (ii) a) LiAlH4/THF/25 °C/3 h,...
Microwave-assisted synthesis of N,N-bis(phosphinoylmethyl)amines and N,N,N-tris(phosphinoylmethyl)amines bearing different substituents on the phosphorus atoms
- Erika Bálint,
- Anna Tripolszky,
- László Hegedűs and
- György Keglevich
Beilstein J. Org. Chem. 2019, 15, 469–473, doi:10.3762/bjoc.15.40
- -tolyl)- or dibenzylphosphine oxide was carried out in acetonitrile at 100 °C for 1 h affording the products with excellent yields (Scheme 4). Then, (aminomethyl)diphenylphosphine oxide (9) was prepared through debenzylation of (benzylaminomethyl)diphenylphosphine oxide (8, Scheme 5). The reduction was
Graphical Abstract
Scheme 1: Synthesis of chiral thiazole-substituted aminophosphine oxides.
Scheme 2: Synthesis of a P-chiral aminophosphine oxide containing a 2-pyridyl moiety.
Scheme 3: Condensation of (octylaminomethyl)dihexylphosphine oxide with paraformaldehyde and di(p-tolyl)phosp...
Scheme 4: Synthesis of (aminomethyl)phosphine oxides 5–7.
Scheme 5: Synthesis of (aminomethyl)diphenylphosphine oxide (9).
Scheme 6: Synthesis of N,N-bis(phosphinoylmethyl)amines 10a,b, 11a,b and 12a,b bearing different substituents...
Scheme 7: Synthesis of N,N-bis(phosphinoylmethyl)amines 13a–c.
Scheme 8: Synthesis of N,N,N-tris(phosphinoylmethyl)amines 14–17.
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
- -one (4S,5S)-20 after reduction of the carbon–iodine bond formed in the primary products of cyclization (via iodonium ion 22). Hydrogenolytic debenzylation preceded oxidation of the hydroxymethyl group to afford diester (4R,5S)-21 which after hydrolysis gave (2R,3S)-2 as the hydrochloride (Scheme 5
Graphical Abstract
Figure 1: Structure of L-glutamic acid.
Figure 2: 3-Hydroxy- (2), 4-hydroxy- (3) and 3,4-dihydroxyglutamic acids (4).
Figure 3: Enantiomers of 3-hydroxyglutamic acid (2).
Scheme 1: Synthesis of (2S,3R)-2 from (R)-Garner's aldehyde. Reagents and conditions: a) MeOCH=CH–CH(OTMS)=CH2...
Scheme 2: Synthesis of (2S,3R)-2 and (2S,3S)-2 from (R)-Garner’s aldehyde. Reagents and conditions: a) H2C=CH...
Scheme 3: Two-carbon homologation of the protected L-serine. Reagents and conditions: a) Fmoc-succinimide, Na2...
Scheme 4: Synthesis of di-tert-butyl ester of (2R,3S)-2 from L-serine. Reagents and conditions: a) PhSO2Cl, K2...
Scheme 5: Synthesis of (2R,3S)-2 from O-benzyl-L-serine. Reagents and conditions: a) (CF3CH2O)2P(O)CH2COOMe, ...
Scheme 6: Synthesis of (2S,3R)-2 employing a one-pot cis-olefination–conjugate addition sequence. Reagents an...
Scheme 7: Synthesis of the orthogonally protected (2S,3R)-2 from a chiral aziridine. Reagents and conditions:...
Scheme 8: Synthesis of N-Boc-protected (2S,3R)-2 from D-phenylglycine. Reagents and conditions: a) BnMgCl, et...
Scheme 9: Synthesis of (2S,3R)-2 employing ketopinic acid as chiral auxiliary. Reagents and conditions: a) Br2...
Scheme 10: Synthesis of dimethyl ester of (2S,3R)-2 employing (1S)-2-exo-methoxyethoxyapocamphane-1-carboxylic...
Scheme 11: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 from (S)-N-(1-phenylethyl)thioacetamide. R...
Scheme 12: Synthesis of N-Boc-protected dimethyl ester of (2S,3R)-2 via Sharpless epoxidation. Reagents and co...
Scheme 13: Synthesis of (2S,3S)-2 from the imide 51. Reagents and conditions: a) NaBH4, MeOH/CH2Cl2; b) Ac2O, ...
Scheme 14: Synthesis of (2R,3S)-2 and (2S,3S)-2 from the acetolactam 55 (PMB = p-methoxybenzyl). Reagents and ...
Scheme 15: Synthesis of (2S,3R)-2 from D-glucose. Reagents and conditions: a) NaClO2, 30% H2O2, NaH2PO4, MeCN;...
Figure 4: Enantiomers of 3-hydroxyglutamic acid (3).
Scheme 16: Synthesis of (4S)-4-hydroxy-L-glutamic acid [(2S,4S)-3] by electrophilic hydroxylation. Reagents an...
Scheme 17: Synthesis of all stereoisomers of 4-hydroxyglutamic acid (3). Reagents and conditions: a) Br2, PBr5...
Scheme 18: Synthesis of the orthogonally protected 4-hydroxyglutamic acid (2S,4S)-73. Reagents and conditions:...
Scheme 19: Synthesis of (2S,4R)-4-acetyloxyglutamic acid as a component of a dipeptide. Reagents and condition...
Scheme 20: Synthesis of N-Boc-protected dimethyl esters of (2S,4R)- and (2S,4S)-3 from (2S,4R)-4-hydroxyprolin...
Scheme 21: Synthesis of orthogonally protected (2S,4S)-3 from (2S,4R)-4-hydroxyproline. Reagents and condition...
Scheme 22: Synthesis of the protected (4R)-4-hydroxy-L-pyroglutamic acid (2S,4R)-87 by electrophilic hydroxyla...
Figure 5: Enantiomers of 3,4-dihydroxy-L-glutamic acid (4).
Scheme 23: Synthesis of (2S,3S,4R)-4 from the epoxypyrrolidinone 88. Reagents and conditions: a) MeOH, THF, KC...
Scheme 24: Synthesis of (2S,3R,4R)-4 from the orthoester 92. Reagents and conditions: a) OsO4, NMO, acetone/wa...
Scheme 25: Synthesis of (2S,3S,4S)-4 from the aziridinolactone 95. Reagents and conditions: a) BnOH, BF3·OEt2,...
Scheme 26: Synthesis of (2S,3S,4R)-4 and (2R,3S,4R)-4 from cyclic imides 106. Reagents and conditions: a) NaBH4...
Scheme 27: Synthesis of (2R,3R,4R)-4 and (2S,3R,4R)-4 from the cyclic meso-imide 110. Reagents and conditions:...
Scheme 28: Synthesis of (2S,3S,4S)-4 from the protected serinal (R)-23. Reagents and conditions: a) Ph3P=CHCOO...
Scheme 29: Synthesis of (2S,3S,4S)-4 from O-benzyl-N-Boc-D-serine. Reagents and conditions: a) ClCOOiBu, TEA, ...
Scheme 30: Synthesis of (2S,3S,4R)-127 by enantioselective conjugate addition and asymmetric dihydroxylation. ...
Figure 6: Structures of selected compounds containing hydroxyglutamic motives (in blue).
Novel solid-phase strategy for the synthesis of ligand-targeted fluorescent-labelled chelating peptide conjugates as a theranostic tool for cancer
- Sagnik Sengupta,
- Mena Asha Krishnan,
- Premansh Dudhe,
- Ramesh B. Reddy,
- Bishnubasu Giri,
- Sudeshna Chattopadhyay and
- Venkatesh Chelvam
Beilstein J. Org. Chem. 2018, 14, 2665–2679, doi:10.3762/bjoc.14.244
- , 28.0; HRMS (ESI) m/z: [M + Na]+ calcd for C30H46N2O9, 601.3096; found, 601.3092. Procedure for debenzylation of benzyl tris(tert-butoxy)-protected DUPA precursor 3 to give (S)-5-(tert-butoxy)-4-(3-((S)-1,5-di-tert-butoxy-1,5-dioxopentan-2-yl)ureido)-5-oxopentanoic acid (4): To a solution of benzyl tris
Graphical Abstract
Figure 1: (a) Structure of universal nova tag resin, (b) structure of H-L-Cys(Trt)-2-ClTrt resin.
Figure 2: (a) PSMA targeted DUPA rhodamine B chelating conjugate 13. (b) Folate receptor targeted pteroate rh...
Scheme 1: Synthesis of PSMA tris(tert-butoxy) protected DUPA ligand 4. Reagents and conditions: (a) Triphosge...
Scheme 2: Attempted synthesis of PSMA targeted DUPA rhodamine B chelating conjugate 13 using Fmoc-Lys(Mtt/Mmt...
Scheme 3: Synthesis of PSMA targeting DUPA rhodamine B chelating conjugate 13. Reagents and conditions: (a) F...
Scheme 4: Synthesis of folate receptor targeting pteroate rhodamine B chelating conjugate 17. Reagents and co...
Figure 3: (i) and (ix) DIC image of LNCaP cells (PSMA+); (ii) binding and internalization of DUPA-rhodamine B...
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
- achieved by N-debenzylation under catalytic hydrogenolysis conditions followed by protection of the liberated amines with CbzCl furnishing fully protected pyrrolidines 14 [35] and 15. Exposure of 14 to a catalytic amount of PTSA (0.04 equiv) in a mixture of CH2Cl2/MeOH 30:1 (v/v) resulted in rapid cleavage
Graphical Abstract
Figure 1: Structures of GMIIb inhibitors.
Scheme 1: Synthesis of pyrrolidines 2a and 3a.
Scheme 2: Synthesis of pyrrolidines 2b,c and 3b,c.
Scheme 3: Synthesis of pyrrolidines 4.
Scheme 4: Synthesis of pyrrolidines 5.
Figure 2: Molecular structure (OLEX2 drawing with adjacent ChemDraw image) of compound 20. Atomic displacemen...
Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline
- Benedikt C. Melzer,
- Jan G. Felber and
- Franz Bracher
Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8
- material 3. Due to the very similar polarities of 3 and 4, chromatographic separation was very tedious, and only 34% of methyl compound 4 was isolated, accompanied by about 30% of starting material 3 and mixed fractions. Debenzylation of 4 by catalytic hydrogenation in methanol solution under palladium
- hydrogenolysis experiments with 5, which were aimed at simultaneous O-debenzylation at the 7-position and conversion of the N,N-dimethylaminomethyl group at C1 into a methyl group. Hydrogenation in presence of palladium as catalyst at 1 bar in the presence or absence of small amounts of sulfuric acid gave the
- highly reactive benzylammonium residue still takes place, but O-debenzylation is predominantly suppressed by this catalyst poison. Finally, poisoning of the catalyst was prevented by simply passing a solution of the methoiodide 7 through a chloride-loaded ion exchanger prior to catalytic hydrogenation
Graphical Abstract
Figure 1: Previously published total syntheses of alkaloid 1 [11,12].
Scheme 1: Total synthesis of alkaloid 1 via direct ring metalation and methylation.
Scheme 2: Total synthesis of alkaloid 1 via the aminomethyl intermediate 5 and selectivity’s found in debenzy...
Intramolecular glycosylation
- Xiao G. Jia and
- Alexei V. Demchenko
Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201
- debenzylation followed by global acetylation to afford product 30. The extension of this approach to convergent oligosaccharide synthesis and reiterative sequencing in presented in Scheme 8. Thus, maltose and lactose disaccharide building blocks were linked via the xylylene tether, and the resulting compound 31
Graphical Abstract
Scheme 1: The mechanistic outline of the intermolecular (a) and intramolecular (b) glycosylation reactions.
Figure 1: Three general concepts for intramolecular glycosylation reactions.
Scheme 2: First intramolecular glycosylation using the molecular clamping.
Scheme 3: Succinoyl as a flexible linker for intramolecular glycosylation of prearranged glycosides.
Scheme 4: Template-directed cyclo-glycosylation using a phthaloyl linker.
Scheme 5: Phthaloyl linker-mediated synthesis of branched oligosaccharides via remote glycosidation.
Scheme 6: Molecular clamping with the phthaloyl linker in the synthesis of α-cyclodextrin.
Scheme 7: m-Xylylene as a rigid tether for intramolecular glycosylation.
Scheme 8: Oligosaccharide synthesis using rigid xylylene linkers.
Scheme 9: Stereo- and regiochemical outcome of peptide-based linkers.
Scheme 10: Positioning effect of donor and acceptor in peptide templated synthesis.
Scheme 11: Synthesis of a trisaccharide using a non-symmetrical tether strategy.
Scheme 12: Effect of ring on glycosylation with a furanose.
Scheme 13: Rigid BPA template with various linkers.
Scheme 14: The templated synthesis of maltotriose in complete stereoselectivity.
Scheme 15: First examples of the IAD.
Scheme 16: Long range IAD via dimethylsilane.
Scheme 17: Allyl-mediated tethering strategy in the IAD.
Scheme 18: IAD using tethering via the 2-naphthylmethyl group.
Scheme 19: Origin of selectivity in boronic ester mediated IAD.
Scheme 20: Arylborinic acid approach to the synthesis of β-mannosides.
Figure 2: Facial selectivity during HAD.
Scheme 21: Possible mechanisms to explain α and β selectivity in palladium mediated IAD.
Scheme 22: DISAL as the leaving group that favors the intramolecular glycosylation pathway.
Scheme 23: Boronic acid as a directing group in the leaving group-based glycosylation method.
