Cover
Half Title
De Gruyter Series in Green Bioactive Heterocycles
Green Bioactive Heterocycles: Volume 1
Non-Conventional Synthesis: Bioactive Heterocycles
Copyright
Preface
Foreword
A brief professional profile of Prof. Anil Kumar Singh
Contents
List of contributors
1. Microwave-assisted catalyst-free synthesis of bioactive heterocycles
1.1 Introduction
1.2 Synthesis of N-heterocycles
1.2.1 Synthesis of pyrrolo[1,10]-phenanthrolines
1.2.2 Synthesis of pyrrolidinyl spirooxindoles
1.2.3 Synthesis of N-substituted 2-methyl-1H-pyrrole-3- carboxylate derivatives
1.2.4 Synthesis of substituted 1,2,3-triazoles
1.2.5 Synthesis of benzimidazole derivatives
1.2.6 Synthesis of ferrocenylimidazolo[2,1-b]-1,3,4-thiadiazoles
1.2.7 Synthesis of 5-substituted 1H-tetrazole
1.2.8 Synthesis of quinoxalinones
1.2.9 Synthesis of 1,4-dihydropyridines
1.2.10 Synthesis of hydroxylated 2,4,6-trisubstituted pyridines
1.2.11 Synthesis of complex fused pyrazole-pyrazines
1.2.12 Synthesis of 1,2,4-triazole-1,4-dihydropyridine derivatives
1.2.13 Synthesis of indeno[1,2-b][1,6]naphthyridine-1,10(2H)-dione
1.2.14 Synthesis of tetrahydropyridine-3-carboxamides
1.2.15 Synthesis of tryptanthrin derivatives
1.2.16 Synthesis of substituted benzo[b][1,4]diazepines
1.3 Synthesis of O-heterocycles
1.3.1 Synthesis of 9H-[1,3]dioxolo[4,5f]chromene derivatives
1.3.2 Synthesis of O-heteroacenes
1.3.3 Synthesis of tetrahydrobenzo[b] pyrans
1.3.4 Synthesis of coumarin and pyrone-fused pyrans
1.3.5 Synthesis of 4-aryl-7,7-dimethyl-5-oxo-3,4,5,6,7, 8-hexahydrocoumarin
1.3.6 Benzylation of naphthols and coumarins
1.3.7 Synthesis of functionalized 2-amino-2H-chromene-3- carboxylates
1.3.8 Synthesis of 2H-pyrans
1.3.9 Synthesis of methyl-7-amino-4-oxo-5-phenyl-2- thioxo-2,3,4,5-tetrahydro-1H-pyrano[2,3-d] pyrimidine-6-carboxylates
1.3.10 Synthesis of novel 1,4-pyranonaphthoquinone derivatives
1.3.11 Synthesis of a series of 1,4-pyranonaphthoquinones
1.4 Synthesis of S-heterocycles
1.4.1 Synthesis of 2-(N-carbamoylacetamide)-substituted 2,3-dihydrothiophenes
1.5 Synthesis of combined heterocycles
1.5.1 Synthesis of thiazol-2(3H)-ones
1.5.2 Synthesis of trisubstituted 1,3-thiazoles
1.5.3 Synthesis of 4-hydroxy-3-arylthiazolidine-2-thiones
1.5.4 Synthesis of hydrazinylthiazole derivatives
1.5.5 Synthesis of 2-substituted benzothiazoles
1.5.6 Synthesis of oxazolo[5,4-b]indoles
1.5.7 Synthesis of 2-(2-oxoalkylidene)-1,3-oxazolidine derivatives
1.6 Synthesis of other heterocycles
1.6.1 Synthesis of 3-hydroxy-2-oxidoles
1.6.2 Synthesis of 3-functionalized 4-hydroxycoumarin
1.7 Conclusions
References
2. Microwave-assisted synthesis of N-heterocycles
2.1 Introduction
2.2 Microwave-assisted synthesis of five-membered heterocycles with one N-atom
2.2.1 Synthesis of pyrrole and its derivatives
2.2.2 Synthesis of pyrrolidines and pyrrolidinones
2.2.3 Synthesis of indole and its derivatives
2.3 Synthesis of five-membered heterocyclic compounds with two N-atoms
2.3.1 Synthesis of imidazole derivatives
2.3.2 Synthesis of pyrazole derivatives
2.4 Synthesis of triazole derivatives
2.5 Synthesis of tetrazole derivatives
2.6 Synthesis of six-membered heterocyclic compounds with one N-atom
2.6.1 Synthesis of pyridine derivatives
2.6.2 Synthesis of quinoline and quinolone derivatives
2.7 Synthesis of six-membered heterocyclic compounds with two N-atoms
2.7.1 Synthesis of pyrimidine derivatives
2.7.2 Synthesis of quinazoline and quinazolinone derivatives
2.8 Synthesis of triazine derivatives
2.9 Synthesis of diazepine and benzodiazepine derivatives
2.10 Synthesis of a few fused heterocyclic compounds containing N-atom
2.11 Conclusions
References
3. Microwave-assisted synthesis of O,S-heterocycles
3.1 Introduction
3.2 Formation of O-heterocyclic moieties under microwave irradiation
3.3 Formation of S-heterocyclic moieties under microwave irradiation
3.4 Conclusions
References
4. Ultrasound-assisted synthesis of N-heterocycles
4.1 Introduction
4.2 Recent research findings
4.2.1 Pyrroles
4.2.2 Pyrazoles
4.2.3 Imidazoles
4.2.4 Oxazoles
4.2.5 Isoxazole
4.2.6 Thiazoles
4.2.7 Oxadiazoles
4.2.8 Thiadiazoles
4.2.9 Triazoles
4.2.10 Tetrazoles
4.2.11 Pyridines
4.2.12 Pyrimidines
4.2.13 Quinolines
4.2.14 Quinoxalines
4.2.15 Phthalazines
4.2.16 Quinazolines
4.2.17 Diazepines/other fused systems
4.3 Conclusions
References
5. Ultrasound-assisted synthesis of O,S-heterocycles
5.1 Introduction
5.2 Ultrasound-assisted synthesis of O-heterocycles
5.2.1 Furans
5.2.2 Benzofurans
5.2.3 Pyrans
5.2.4 Chromenes
5.2.5 Flavones
5.3 Ultrasound-assisted synthesis of S-heterocycles
5.3.1 Thiophenes
5.4 Ultrasound-assisted synthesis of O,S-heterocycles
5.5 Conclusions
References
6. Ultrasound-assisted synthesis of bioactive 1,2,3-triazoles via click reactions
6.1 Introduction
6.2 Ultrasound-assisted click reactions
6.2.1 Synthesis of 1,2,3-triazoles using sodium azide
6.2.1.1 Synthesis of 1,4-dialkyl/aryl-substituted-1,2,3-triazoles
6.2.1.2 Synthesis of diaryl sulfone-coupled 1,2,3-triazoles
6.2.1.3 Synthesis of N-(benzo[d]thiazol-2-yl)-2-(4-substituted-1H-1,2,3-triazol-1-yl)acetamides
6.2.1.4 Synthesis of fluorinated 1,2,4-triazole-benzothiazole-functionalized 1,2,3-triazoles
6.2.2 Synthesis of 1,2,3-triazoles using aryl azide
6.2.2.1 Synthesis of 5ʹ-(4-substituted-1H-1,2,3-triazol-1-yl)spiro[[1,3]dioxolane-2,3ʹ-indolin]-2ʹ-one
6.2.2.2 Synthesis of selanyl-1,2,3-triazoles
6.2.2.3 Synthesis of 4-(4-phenyl-1H-1,2,3-triazol-1-yl)quinoline
6.2.3 Synthesis of 7-(3-(4-aryloxymethyl-1,2,3-triazol-1-yl)propoxy)-5-hydroxyflavone using alkyl azide
6.2.4 Synthesis of 1,2,3-triazole nucleosides
6.3 Conclusions
References
7. Photoirradiated synthesis of bioactive heterocycles
7.1 Introduction
7.2 History of heterocycles
7.3 Classifications of heterocycles
7.3.1 Three-membered rings with one or two heteroatoms
7.3.2 Four-membered rings with one or two heteroatoms
7.3.3 Five-membered rings with one or two heteroatoms
7.3.4 Six-membered rings
7.4 Synthesis of heterocycles
7.4.1 Synthesis of N-containing heterocycles using photoirradiation
7.4.2 Synthesis of five-membered N-heterocycles
7.4.3 Synthesis of O-heterocycles
7.4.4 O,N-Heterocycle synthesis
7.4.5 Synthesis of S-containing heterocycles
7.4.6 Heterocycles containing nitrogen and sulfur
7.5 Named reactions leading to heterocycles
7.5.1 Paterno–Buchi reaction
7.5.2 Barton reaction
7.5.3 Hofmann–Loffler–Freytag reaction
7.6 Conclusions
References
8. Synthesis of heterocycles through electrolysis
8.1 Introduction
8.2 Electrosynthesis of heterocyclic compounds through intramolecular cyclization
8.2.1 Intramolecular cyclization involving oxidative formation of carbon–carbon bonds
8.2.2 Intramolecular cyclization involving reductive formation of carbon–carbon bonds
8.2.2.1 Electroreductive generation of carbon–carbon bond utilizing unsaturated halide compounds
8.2.2.2 Electroreductive generation of carbon–carbon bond utilizing unsaturated ketones
8.2.2.3 Electroreductive generation of carbon–carbon bond based on aromatic imines and cyclic imides
8.2.3 Electrosynthesis of heterocycles via formation of carbon–hetero atom bond
8.2.3.1 Electrooxidative generation of carbon–nitrogen bonds
8.2.3.2 Electroreductive generation of carbon–nitrogen bonds
8.2.3.3 Electrooxidative generation of carbon-oxygen bonds
8.2.3.3.1 Intramolecular electrochemical reaction of electron-rich olefin and alcohol nucleophile
8.2.3.3.2 Iminium cations-mediated synthesis of oxygen-based heterocycles
8.2.3.3.3 Synthesis of heterocycles via reaction of unactivated alkenes and Schiff’s base with oxygen nucleophiles
8.3 Electrochemical synthesis of heterocycles via intermolecular cyclization
8.3.1 Synthesis of heterocyclic compounds involving electrogenerated benzoquinones and analogues
8.3.2 Electrosynthesis of heterocyclic compounds via cycloaddition reaction
8.3.3 Electrochemical synthesis of heterocyclic compounds mediated by electrogenerated anions
8.4 Conclusions
References
9. Flow synthesis of oxygen and nitrogen heterocycles
9.1 Introduction
9.2 Flow synthesis of 1,3-triazoles
9.3 Flow synthesis of telemisartan
9.4 Domino synthesis of azetidinium salts in batch and flow mode
9.5 Synthesis of 3-aminoimidazo[1,2-a]-pyrimidines using flow mechanism
9.6 Access of biologically interesting pyrazole derivatives via flow mode
9.7 Synthesis of nifedipine through flow synthesis
9.8 Flow reaction for the synthesis of benzodiazepines
9.9 Synthesis of fluconazole using multistep flow technique
9.10 Combination of continuous flow with acid catalyst for the synthesis of 3-indolyl naphthoquinone
9.11 High-temperature and pressure flow synthesis of 2-substituted azoles
9.12 Flow synthesis of pyridine-oxazoline (PyOX) ligands
9.13 Continuous-flow synthesis of the URAT1 inhibitor
9.14 Continuous organocatalytic flow synthesis of 2-substituted oxazolidinones
9.15 Direct azidation of alcohols and peroxides and tandem synthesis of quinoxalinone, benzooxazinone, and triazole derivatives using the flow technique
9.16 Flow synthesis of fused pyrimidinone and quinolone derivatives
9.17 Quinazolidione synthesis using integrated CO2 capture-fixation chemistry via interfacial ionic liquid catalyst in laminar gas/liquid flow
9.18 Continuous-flow access to API 7-ethyltryptophol
9.19 Conclusions
Refrences
10. Ball-milling-promoted synthesis of bioactive heterocycles
10.1 Introduction
10.2 Synthesis of bioactive heterocyclic compounds
10.2.1 Synthesis of naphthopyran derivatives
10.2.2 Synthesis of quinoxaline derivatives
10.2.3 Synthesis of pyrimidinone derivatives
10.2.4 Synthesis of pyrrole derivatives
10.2.5 Synthesis of indole derivatives
10.2.6 Synthesis of pyrazole derivatives
10.2.7 Synthesis of pyrazoline derivatives
10.2.8 Synthesis of triazole derivatives
10.2.9 Synthesis of benzimidazole, benzoxazole, and benzthiazole derivatives
10.2.10 Synthesis of dibenzophenazine derivatives
10.2.11 Synthesis of oxazolidinone derivatives
10.2.12 Synthesis of xanthene derivatives
10.2.13 Synthesis of flavone derivatives
10.3 Conclusions
References
11. Synthesis of bioactive heterocycles via click reaction
11.1 Introduction
11.2 Applications of click reactions for the synthesis of various bioactive heterocycles
11.2.1 Synthesis of pyrrolizines
11.2.2 Synthesis of azepines
11.2.3 Synthesis of isoquinolines, quinolines, and pyridines
11.2.4 Synthesis of quinoline-based bioactive molecules using diversity-oriented synthesis (DOS)
11.2.5 Synthesis of pyridines
11.3 Modifications of alkaloids
11.3.1 Cinchona alkaloids
11.3.2 Colchicine alkaloids
11.3.3 Berberine alkaloids
11.4 Bioactivity of triazoles
11.4.1 Antibacterial activity
11.4.2 Anticancer activity
11.5 Conclusions
References
12. Synthesis of bioactive heterocycles by nanocatalysis
12.1 Introduction
12.2 What is nanocatalysis?
12.3 Synthesis of effective nanocatalysts
12.4 Improvement of NP catalytic reactivity
12.4.1 Size effect
12.4.2 Morphological effect
12.4.3 Composition effect
12.5 Nanocatalysts in the synthesis of biologically active heterocyclics
12.5.1 Synthesis of four-membered heterocycles
12.5.1.1 β-Lactam synthesis
12.5.2 Synthesis of five-membered heterocycles
12.5.2.1 Pyrrole
12.5.2.2 Indole
12.5.2.3 Pyrazoles
12.5.2.4 Imidazoles
12.5.2.5 Triazole
12.5.2.6 Tetrazole
12.5.2.7 Furan derivatives
12.5.2.8 Thiazole
12.5.3 Synthesis of six-membered heterocycles
12.5.3.1 Pyran
12.5.3.2 Pyridines
12.5.3.3 Quinolines
12.5.3.4 Quinazolines
12.5.3.5 Pyrimidines
12.5.4 Synthesis of seven-membered heterocycles
12.5.4.1 Diazepines
12.6 Conclusions
References
13. Enantioselective metal-catalyzed domino reactions in the total synthesis of bioactive heterocycles
13.1 Introduction
13.2 Bisphosphine ligands
13.3 Bisoxazoline ligands
13.4 P,N-ligands
13.5 Other ligands
Abbreviations
References
14. Synthesis of pharmacologically significant pentathiepins: a journey from harsh to mild conditions
14.1 Introduction
14.1.1 Pentathiepins: a special class of cyclic polysulfides
14.2 Synthesis
14.2.1 Metal-free approaches
14.2.1.1 Synthesis of benzopentathiepins
14.2.1.2 Synthesis of heterocycle fused pentathiepins
14.2.2 Metal mediated syntheses
14.2.2.1 Synthesis mediated by tin
14.2.2.2 Synthesis mediated by titanium
14.2.2.3 Synthesis mediated by molybdenum
14.3 Reactions of pentathiepins
14.3.1 Reactions involving the pentathiepin ring
14.3.1.1 Thermal decomposition
14.3.1.2 Reduction
14.3.1.3 Oxidation
14.3.1.4 Nucleophilic attack
14.3.1.5 Ring contraction to 1,2,3-trithiol
14.3.1.6 Sulfur replacement by carbon
14.3.1.7 Dimerization to tetrathiocines
14.3.1.8 1,2,4-trithiins
14.3.1.9 1,4-Thianthrenes
14.3.1.10 1,4-dithiins and 1,4-dithians
14.3.2 Reactions involving (hetero)aromatic backbone
14.4 Physical and theoretical properties of pentathiepins
14.4.1 X-ray crystallography
14.4.2 NMR spectroscopy
14.4.3 Mass spectrometry
14.4.4 Vibrational spectroscopy
14.4.5 UV-Vis spectroscopy
14.4.6 Conformation and chirality
14.4.7 DFT calculations
14.5 Biological activity and applications of pentathiepins
14.5.1 Naturally occurring pentathiepins
14.5.2 Benzopentathiepin analogues
14.5.3 Pentathiepins with a heterocyclic backbone
14.6 Other applications of pentathiepins
14.7 Conclusions
References
15. Developments in the synthesis of ring phosphine oxides
15.1 Introduction
15.2 Synthesis of five-membered P-heterocycles
15.3 Synthesis of six-membered P-heterocycles
15.4 Special cases: large P-heterocycles and bridged derivatives
15.5 Conclusions
References
16. Total synthesis of bioactive heterocyclic scaffolds via Pauson Khand reaction
16.1 Introduction
16.2 Terpenes
16.2.1 Monoterpenoids
16.2.1.1 Synthesis of iridoids
16.2.2 Sesquiterpenes
16.2.2.1 Synthesis of (2R)-hydroxynorneomajucin
16.2.2.2 Synthesis of 2-epi-a-cedren-3-one
16.2.2.3 Synthesis of sinodielide A
16.2.3 Diterpenoids
16.2.3.1 Synthesis of waihoensene
16.2.3.2 Synthesis of marrubin
16.2.3.3 Synthesis of crinipellin A
16.2.3.4 Synthesis of 5-epi-cyanthiwigin
16.2.3.5 Synthesis of 4-desmethyl rippertenol and 7-epi-rippertenol
16.2.4 Sesterterpenoids
16.2.4.1 Synthesis of astellatol
16.2.4.2 Synthesis of retigeranic acid
16.2.5 Triterpenoid
16.2.5.1 Synthesis of haperforin G
16.2.6 Special class of terpenoids
16.2.6.1 Synthesis of spirochensilide A
16.2.6.2 Synthesis of caribenol A
16.3 Alkaloids
16.3.1 C19 diterpenoid alkaloids
16.3.2 Synthesis of (–)-daphlongamine H and (–)-isodaphlongamine H
16.3.3 Synthesis of lycopoclavamine-A
16.3.4 Synthesis of hybridaphniphylline B
16.3.5 Total synthesis of (–)-allosecurinine
16.3.6 Synthesis of streptazone A
16.4 Steroids
16.4.1 Synthesis of bufospirostenin A
16.5 Conclusion
References
17. Nonconventional approaches in drug discovery
17.1 Introduction
17.2 Reverse pharmacology or rational drug design
17.3 Drug repurposing or drug repositioning
17.4 Computer-aided drug discovery (CADD)
17.5 High-throughput screening (HTS)
17.6 Conclusions
References
Index