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

Efficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a-c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity

Scalable synthesis of (1-cyclopropyl)cyclopropylamine hydrochloride

1-Cyclopropylcyclopropanecarboxylic acid (2), which is accessible on a large scale (900 mmol) from 1-bromo-1-cyclopropylcyclopropane (1) in 64% yield (89% on a 12.4 mmol scale), has been subjected to a Curtius degradation employing the Weinstock protocol to furnish the N-Boc-protected (1-cyclopropyl)cyclopropylamine 3 (76%). Deprotection of 3 with hydrogen chloride in diethyl ether gave the (1-cyclopropyl)cyclopropylamine hydrochloride (4·HCl) in 87% yield

Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

4-Fluoropyrazole systems may be prepared by a single, sequential telescoped two-step continuous gas/liquid–liquid/liquid flow process from diketone, fluorine gas and hydrazine starting materials

(2 R

Efficient and scalable syntheses of enantiomerically pure (2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-mono(di,tri)fluoromethylcyclopropyl]alanines 9a-c, as well as allo-D-threonine (4) and (2S,3R)-β-methylphenylalanine (3), using the Belokon' approach with (S)- and (R)-2-[(N-benzylprolyl)amino]benzophenone [(S)- and (R)-10] as reusable chiral auxiliaries have been developed. Three new fluoromethyl analogues of the naturally occurring octadepsipeptide hormaomycin (1) with (fluoromethylcyclopropyl)alanine moieties have been synthesized and subjected to preliminary tests of their antibiotic activity

9,10-Dioxa-1,2-diaza-anthracene derivatives from tetrafluoropyridazine

Reaction of tetrafluoropyridazine with catechol gives a tricyclic 9,10-dioxa-1,2-diaza-anthracene system by a sequential nucleophilic aromatic substitution ring annelation process, further extending the use of perfluoroheteroaromatic derivatives for the synthesis of unusual polyfunctional heterocyclic architectures. The tricyclic scaffold reacts with amines and sodium ethoxide providing a short series of functional 9,10-dioxa-1,2-diaza-anthracene systems

Annelation of perfluorinated heteroaromatic systems by 1,3-dicarbonyl derivatives

Reactions of various perfluorinated heteroaromatic substrates such as tetrafluoro-4-cyanopyridine, tetrafluoropyrazine and tetrafluoropyridazine with 1,3-dicarbonyl systems gave corresponding [5,6]-ring fused furo derivatives. Subsequent reactions of the [5,6] bicyclic scaffolds with nucleophiles gave some highly functionalised heteroaromatic systems

9,10-Dioxa-1,2-diaza-anthracene derivatives from tetrafluoropyridazine

Abstract Reaction of tetrafluoropyridazine with catechol gives a tricyclic 9,10-dioxa-1,2-diaza-anthracene system by a sequential nucleophilic aromatic substitution ring annelation process, further extending the use of perfluoroheteroaromatic derivatives for the synthesis of unusual polyfunctional heterocyclic architectures. The tricyclic scaffold reacts with amines and sodium ethoxide providing a short series of functional 9,10-dioxa-1,2-diaza-anthracene systems