Steroid total synthesis. 3. 9 , 10 -testosterone

The total synthesis of 9β, 10α-testosterone via a BCD-tricyclic intermediate is described. The latter compound – 17β-hydroxy-des-A-androst-9-en-5-one – was obtained in optically active form by our previously reported scheme, using an efficient resolution step early in the synthesis. New results regarding the asymmetric induction step are also discussed.     

HPTLC Monitoring of the Biocatalytic Synthesis of Quinoxalinone Derivatives in a One-Pot Reaction

JPC – Journal of Planar Chromatography – Modern TLC - High-performance thin-layer chromatography has been used to follow the synthesis of some quinoxalinone derivatives by biocatalysis...     

Mononuclear Tetraamineplatinum(II) Complexes: Synthesis,Anticancer Activity,DNA Binding,and Cellular Uptake

The synthesis of three bis[(tert‐butoxy)carbonyl]‐protected (tetramine)dichloroplatinum complexes 2a – c of formula cis‐[PtCl₂(LL)] and of their cationic deprotected analogs 3a – c and their evaluation with respect to in vitro cytotoxicity, intramolecular stability, DNA binding, and cellular uptake is reported. The synthesis comprises the complexation of K₂[PtCl₄] with di‐N‐protected tetramines 1a – c to give 2a – c and subsequent acidolysis, yielding 3a – c . The cytotoxicity of the complexes is in direct relation to the length of the polyamine. Complexes 3a – c display a significant higher affinity for CT DNA as well as for cellular DNA in A2780 cells than cisplatin.     

Efficient Synthesis of α‐Benzylidene‐γ‐methyl‐γ‐butyrolactones

A concise synthesis of α‐benzylidene‐γ‐methyl‐γ‐butyrolactones 5a – g from substituted benzaldehydes is described. Compounds 1a – g on reaction with phosphorane 2 , provide the pentenoates 3a – g , which can be hydrolyzed to the acids 4a – g . The latter are cyclized to the corresponding butyrolactones 5a – g in excellent yields. The pentenoates 3a – g , on acid catalyzed cyclization, also provide 5a – g in very high yields.     

Towards an Integrated Platform for Combinatorial Library Synthesis and Screening

JPC – Journal of Planar Chromatography – Modern TLC - Combined technology for the synthesis, separation, screening, and analysis of combinatorial libraries is described. The technique...     

A Simple Synthesis of 5‐(2‐Aminophenyl)‐1H‐pyrazoles

A four‐step synthesis of 1‐substituted 5‐(2‐aminophenyl)‐1H‐pyrazoles 5 as a novel type of histamine analogs and versatile building blocks for further transformations was developed. The synthesis starts from commercially available 2‐nitroacetophenone ( 12 ), which is converted into the enamino ketone 13 as the key intermediate. Cyclization of the key intermediate 13 with monosubstituted hydrazines 14a – 14l afforded the 5‐(2‐nitrophenyl)‐1H‐pyrazoles 17a – 17l . Finally, catalytic hydrogenation of the nitro compounds 17a, 17c – 17e , and 17g – 17j furnished the title compounds 5a, 5c – 5e , and 5g – 5j , respectively, in good yields. As demonstrated by some further transformations, additional functionalization of compounds 17 and 5 is feasible, either by electrophilic substitution at C(4) of the pyrazole ring, or at the NH₂ group.     

ChemScreen: Planar Synthesis,Separation and Screening of Antioxidants

JPC – Journal of Planar Chromatography – Modern TLC - The method described herein is a very powerful tool for rapid synthesis, separation, and screening of combinatorial libraries on...     

Synthesis of bicyclic tripeptides inspired by the ABC-ring system of vancomycin through ruthenium-based cyclization chemistries

The synthesis of a bicyclic tripeptide that mimics the ABC ring system of vancomycin is described by using a ring closing metathesis (RCM) – peptide coupling – ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) strategy.     

Rearrangement of Cephem Bromohydrins to Thiazepine Derivatives

A new rearrangement of cephem bromohydrins 2 – 5 to thiazepine derivatives 7 – 8 is described. The structure of the rearrangement product is established by an independent synthesis. The probable mechanism of the above rearrangement is discussed.     

A Convenient Synthesis of Bipyrido‐Fused Coumarins and Their Biological Evaluation

A convenient and efficient strategy has been devised for the synthesis of bipyrido‐fused coumarins employing Kröhnke's pyridine synthesis approach. In the present work, 4‐hydroxycoumarins 1a – d were reacted with appropriate chalcones 2a – c to afford desired bipyridyl‐fused coumarins 3a – l . The structures of all the newly synthesized compounds 3a – l were ascertained by IR, ¹H NMR, ¹³C NMR, mass spectral data, and elemental analyses. The compounds were further evaluated for their antimicrobial response against representative panel of pathogens, and the results thus obtained were compared with those of standard drugs. Few of the derivatives 3c , 3f , and 3i exhibited promising potency.     

Synthesis and Characterization of Phosphate-Catecholate Chelated Nd(III), Zr(IV), and Al(III) Complexes

Metal phosphates are important catalysts and materials in synthesis chemistry. Herein, we describe the synthesis and characterization of phosphate-catecholate chelated Nd(III), Zr(IV) and Al(III) chlorides ( 2 – 5 ). These species are achieved via ethyl chloride elimination reaction of oxophosphoranes with corresponding metal chlorides. The product 2 – 5 represent a new serial of monometallic and bimetallic phosphate-catecholate chelated metal complexes stabilized by both P−O and catecholate-O donors. These findings pave the way for future explorations of such species in catalysis.     

Nucleotides,Part LXI,Phthaloyl Strategy: A New Concept of Oligonucleotide Synthesis

A new alternative strategy of oligonucleotide synthesis was developed by use of the phthaloyl protecting group for the exocyclic amino functions of the nucleobases (see 9 – 12 ). This approach combines the advantages of cheap and easily accessable monomeric building blocks (see 17 – 20 ), standard machine-aided oligonucleotide synthesis, and a fast deprotection protocol which is orthogonal to the cleavage procedure from the solid support. The crude oligonucleotides show high purity and require, in general, no further chromatographic purification.     

β-Cleavage of Bis(homoallylic) Potassium Alkoxides. Preparation of 3-Hydroxypropyl and 4-Hydroxybutyl Propenyl Ketones from γ- and δ-Lactones. Synthesis of (±)-Rose oxide

Starting from γ- and δ-lactones 1 – 3 , a two-step preparation of 3-hydroxypropyl and 4- hydroxybutyl propenyl ketones 10 – 18 is described, involving as the key step the β-cleavage of the bis(homoallylic) potassium alkoxides 4a – 9a . The novel methodology is illustrated by a short synthesis of (±)-rose oxide( 20 ).     

Microwave‐Assisted Synthesis and Characterization of Novel Sulfonamide‐β‐Lactam Conjugates

New sulfonamide‐β‐lactam molecular conjugates 3 ( a – l ) have been generated through microwave‐assisted synthesis. β‐Lactams 1 ( a – e ) reacted with selected sulfonamides under microwave irradiation in the presence of KI and mediated by K₂CO₃ to afford conjugates 3 ( a – l ). All new compounds were structurally authenticated by spectroscopic and elemental analyses.     

7-Halogenated 7-Deaza-2′-deoxyinosines

The synthesis of the 7-deaza-2′-deoxyinosine derivatives 3a – c with chloro, bromo, and iodo substituents at position 7 is described. Glycosylation of the 7-halogenated 6-chloro-7-deazapurines 4a – c or of the 7-halogenated 6-chloro-7-deaza-2-(methylthio)purines 9a – c with 2-deoxy-3,5-di-O-(4-toluoyl)-α-D -erythro-pentofuranosyl chloride ( 5 ) furnished the intermediates 7a – c and 11a – c , respectively, which gave, upon deprotection, the desired nucleosides 3a – c .     

Synthesis and Cyclization of 8‐Formyl‐2‐(phenoxymethyl)quinoline‐3‐carboxylic Acids

A facile synthesis of a series of new quinoline‐8‐carbaldehyde compounds, namely 8‐formyl‐2‐(phenoxymethyl)quinoline‐3‐carboxylic acids ( 4a – 4h ) and 13‐oxo‐6,13‐dihydro[1]benzoxepino[3,4‐b]quinoline‐8‐carbaldehyde ( 5a – 5g ) is described, involving the one‐pot synthesis reaction of ethyl 2‐(chloromethyl)‐8‐formylquinoline‐3‐carboxylate ( 3 ) with substituted phenols followed by the intramolecular cyclization reaction via the treatment with polyphosphoric acid (PPA). Quinoline‐8‐carbaldehydes 4a – 4h and 5a – 5g are novel and their structures were supported by IR, ¹H NMR, ¹³C NMR, MS and elemental analysis.     

Cu (I) Catalyzed One Pot SN‐Click Reactions of Halogenated Coumarins and 1‐aza‐coumarins

A one pot three component, copper catalyzed azide‐alkyne cycloaddition reaction has been employed for the synthesis of bis‐coumarinyl triazoles ( A – D ) using 4‐chloro, 4‐bromomethyl, 3‐bromoacetyl and 4‐bromomethyl‐1‐aza‐coumarins ( I – IV ), sodium azide, and coumarin propargyl ethers ( V – IX ) in moderate yields.     

Selbstorganisation von Molekülen über kovalente Bindungen: Selektive Tetramerisierung eines p-Chinodimethans

Self-Organization of Molecules by Covalent Bonds: Selective Tetramerization of a p -Quinodimethane A simple and efficient synthesis of paracyclophane derivatives based on self-organization of a quinodimethane is described. Treatment of dibromides 5a – d with mercury afforded in high yield the macrocyclic compounds 6a – d . Interestingly, these compounds change the color on grinding and heating, from colorless to violet. The structure of 6a – d was determined by spectroscopic analyses. Single-crystal structure analysis of 6b and 6c confirmed the proposed structure.     

An alternative synthesis of the lipophilic tail portion of abediterol using linear-selective hydroformylation

Abediterol is a compound currently in development for the treatment of respiratory disease at AstraZeneca. In this work we employ hydroformylation, an under-utilised reaction in the synthesis of pharmaceutical intermediates, as a key step to access the lipophilic amine portion of this molecule. The route described herein addresses some of the issues identified in the original route. Namely, hazardous materials are avoided and increased levels of control – from a process chemistry point of view – are demonstrated, with isolation of intermediates possible at multiple points in the synthesis. This work provides ‘proof-of-concept’ for an alternative synthetic route and provides high-quality material using a series of robust transformations.     

Combining spiro-fused cyclohexadienone – tetrahydrofuran ring system with glycine: Asymmetric synthesis of a new class of α-amino acid derivatives

Herein, we present the asymmetric synthesis of spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives as a new class of nonproteinogenic α-amino acid derivatives. Starting from commercially available 2-allylphenols, key β-hydroxy-α-amino esters were synthesized via high-yielding multi-step reaction sequences involving Sharpless asymmetric dihydroxylation as the chirality induction step. PhI(OAc)₂-mediated oxidative dearomatization – spirocyclization of phenol-tethered β-hydroxy-α-amino esters efficiently produced the corresponding spiro-fused cyclohexadienone – tetrahydrofuran-embedded glycine derivatives, providing a general route to this hitherto-unreported class of compounds that are equipped with three privileged scaffolds (cyclohexadienone – tetrahydrofuran – α-amino ester).