N,N-Dialkyl-N′-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part XIV. Synthesis and Reactivity of the New Benzo[4,5]imidazo[1,2-b][1,2,6]thiadiazine Ring System

2018 ◽  
Vol 71 (1) ◽  
pp. 58 ◽  
Author(s):  
Dylan Innes ◽  
Michael V. Perkins ◽  
Andris J. Liepa ◽  
Craig L. Francis
Keyword(s):  
Medicinal Chemistry ◽  
Ring System ◽  
Heterocyclic Synthesis ◽  
Alkyl Derivatives ◽  
Regioselective Reactions ◽  
Novel Scaffold ◽  
Derivatives Of ◽  
Related Compounds

N,N-Dialkyl-N′-chlorosulfonyl chloroformamidines 1 underwent regioselective reactions with the 1,3-NCC bis-nucleophilic 1H-benzimidazole-2-acetonitriles 4 and related compounds to produce benzo[4,5]imidazo[1,2-b][1,2,6]thiadiazine dioxides 6, 9, 12, and 14, representatives of a new ring system. Reaction of dichlorides 1 with trifluoroacetyl derivative 16 afforded benzo[4,5]imidazo[1,2-c]pyrimidines 19 and 20. An N-acyl and some N-alkyl derivatives of benzimidazo-thiadiazines 6 were prepared to demonstrate the potential of this new ring system as a novel scaffold for synthetic and medicinal chemistry applications. Treatment of the 4-cyano-5-methyl-benzimidazo-thiadiazine 26c with LiAlH4 resulted in an unexpected and remarkable conversion of the nitrile to give the 4,5-dimethyl-benzimidazo-thiadiazine 29.

N,N-Dialkyl-N′-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part VII 4-Dialkylamino[1,2,3,5]Benzoxathiadiazepine Dioxides and 4-Dialkylamino-[2,1,3,5]Benzothiatriazepine Dioxides

2008 ◽  
Vol 61 (10) ◽  
pp. 785 ◽  
Author(s):  
Teresa Cablewski ◽  
Craig M. Forsyth ◽  
Craig L. Francis ◽  
Andris J. Liepa ◽  
Victor Tran
Keyword(s):  
Medicinal Chemistry ◽  
Ring System ◽  
Heterocyclic Synthesis ◽  
Derivatives Of ◽  
Acyl Derivatives

N,N-dialkyl-N′-chlorosulfonyl chloroformamidines 1 reacted with 2-aminophenols 2 to give 4-dialkylamino[1,2,3,5]benzoxathiadiazepine dioxides 3, which are examples of a new ring system. Reaction of 1 with 1,2-diaminobenzenes 7 afforded 4-dialkylamino[2,1,3,5]benzothiatriazepine dioxides 8 and 9, which are new derivatives of a rare ring system. Some N-alkyl and N-acyl derivatives of 3 and 8 were prepared to demonstrate the potential of these compounds as novel scaffolds for synthetic and medicinal chemistry.

The Meisenheimer Rearrangement in Heterocyclic Synthesis. IV. Derivatives of the 2H,6H-1,5,4-Benzodioxazocine and 7H-1,6,5-Benzodioxazonine Ring Systems: X-Ray Crystal Structure of 10-Methoxy-5-methyl-7-phenyl-2,3,4,5-tetrahydro-7H-1,6,5-benzodioxazonine

1988 ◽  
Vol 41 (3) ◽  
pp. 293 ◽  
Author(s):  
JB Bremner ◽  
EJ Browne ◽  
LM Engelhardt ◽  
IWK Gunawardana ◽  
AH White
Keyword(s):  
Molecular Structure ◽  
Crystal Structure ◽  
Crystal And Molecular Structure ◽  
Ring System ◽  
Heterocyclic Synthesis ◽  
Rearrangement Product ◽  
Ring Systems ◽  
X Ray ◽  
Derivatives Of ◽  
Moderate Yield

Meisenheimer rearrangement of the N-oxides (4) derived from a series of 5-aryl-4-methyl-2,3,4,5-tetrahydro-1,4-benzoxazepines (3) gave rise to eight derivatives (5) of the new 2H,6H-1,5,4-benzodioxazocine ring system. Reaction of 9-methoxy-5-methyl-6-phenyl-3,4,5,6- tetrahydro-2H-1,5-benzoxazocine (6) with 3-chloroperoxybenzoic acid gave an unstable N-oxide (7). A Meisenheimer rearrangement product from (7), 10-methoxy-5-methyl-7-phenyl-2,3,4,5-tetrahydro-7 H-1,6,5- benzodioxazonine (8), the first example of this ring system, was isolated directly in moderate yield on oxidation of (6) with cooling. The crystal and molecular structure of (8) has been determined by X-ray crystallographic methods.

Synthesis and Cytostatic Activity of N-[2-(Phosphonomethoxy)alkyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds

2001 ◽  
Vol 66 (10) ◽  
pp. 1545-1592 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Votruba ◽  
Eva Tloušťová ◽  
Milena Masojídková
Keyword(s):  
Cytostatic Activity ◽  
Secondary Amines ◽  
Dimethylformamide Dimethylacetal ◽  
Alkyl Derivatives ◽  
Derivatives Of ◽  
Related Compounds ◽  
Substituted Adenines

N6-Substituted adenine and 2,6-diaminopurine derivatives of 9-[2-(phosphonomethoxy)- ethyl] (PME), 9-[(R)-2-(phosphonomethoxy)propyl] [(R)-PMP] and enantiomeric (S)-PMP series were synthesized by reactions of primary or secondary amines with 6-chloro-9-{[2-(diisopropoxyphosphoryl)methoxy]alkyl}purines (26-28) or 2-amino-6-chloro-9-{[2-(diisopropoxy- phosphoryl)methoxy]alkyl}purines (29-31) followed by treatment of the diester intermediates32with bromo(trimethyl)silane and hydrolysis. Diesters32were also obtained by reaction ofN6-substituted purines with synthons23-25bearing diisopropoxyphosphoryl group. Alkylation of 2-amino-6-chloropurine (9) with diethyl [2-(2-chloroethoxy)ethyl]phosphonate (148) gave the diester149which was analogously converted toN6-substituted 2,6-diamino- 9-[2-(2-phosphonoethoxy)ethyl]purines151-153. Alkylation ofN6-substituted 2,6-diaminopurines with (R)-[(trityloxy)methyl]oxirane (155) followed by reaction of thus-obtained intermediates156with dimethylformamide dimethylacetal and condensation with diisopropyl [(tosyloxy)methyl]phosphonate (158) followed by deprotection of the intermediates159gaveN6-substituted 2,6-diamino-9-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]purines160-163. The highest cytostatic activityin vitrowas exhibited by the followingN6-derivatives of 2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (PMEDAP): 2,2,2-trifluoroethyl (53), allyl (54), [(2-dimethylamino)ethyl] (68), cyclopropyl (75) and dimethyl (91). In CCRF-CEM cells, the cyclopropyl derivative75is deaminated to the guanine derivative PMEG (3) which is then converted to its diphosphate.

N,N-Dialkyl-N'-Chlorosulfonyl Chloroformamidines in Heterocyclic Synthesis. Part VIII. Novel Pyrazolo-Fused Oxathiadiazines and Thiatriazoles

2010 ◽  
Vol 63 (4) ◽  
pp. 659 ◽  
Author(s):  
Craig M. Forsyth ◽  
Craig L. Francis ◽  
Saba Jahangiri ◽  
Andris J. Liepa ◽  
Michael V. Perkins ◽  
...  
Keyword(s):  
Recent Work ◽  
Major Product ◽  
Ring System ◽  
Heterocyclic Synthesis ◽  
Ring Systems ◽  
The Core ◽  
Derivatives Of

N,N-dialkyl-N′-chlorosulfonyl chloroformamidines 1 reacted with pyrazol-3-ones 2 under a variety of conditions to give pyrazolo[2,3-e][1,2,3,5]oxathiadiazine dioxides 3 and pyrazolo[3,2-b][1,4,3,5]oxathiadiazine dioxides 5, and frequently, one or both of pyrazolo[1,2-b][1,2,3,5]thiatriazole 1,1,5-trioxides 4 and 1,1,7-trioxides 6. In all reactions, the pyrazolo[3,2-b][1,4,3,5]oxathiadiazine 5 was the major product, with the pyrazolo[2,3-e][1,2,3,5]oxathiadiazine 3 being a significant product in the absence of base. Prior to our recent work, the core ring systems of compounds 3 and 5 had not been reported and compounds 4 and 6 are new derivatives of a rare ring system.

Synthesis of Optically Active N6-Alkyl Derivatives of (R)-3-(Adenin-9-yl)-2-hydroxypropanoic Acid and Related Compounds

2003 ◽  
Vol 68 (5) ◽  
pp. 931-950 ◽  
Author(s):  
Marcela Krečmerová ◽  
Miloš Buděšínský ◽  
Milena Masojídková ◽  
Antonín Holý
Keyword(s):  
Nmr Spectra ◽  
Enantiomeric Purity ◽  
Optically Active ◽  
Secondary Amines ◽  
H Nmr ◽  
Alkyl Derivatives ◽  
Optically Pure ◽  
Derivatives Of ◽  
Related Compounds

Reaction of ethyl (R)-oxiranecarboxylate (2a) with various nucleobases (adenine, 6-chloropurine, thymine, cytosine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one and 4-methoxypyrimidin-2(1H)-one) afforded ethyl 3-substituted-2-hydroxypropanoates 4-10. Enantioselectivity of this reaction is dependent on the type of the base: 6-chloropurine, N6-benzoyladenine, 4-methoxy-5-methylpyrimidin-2(1H)-one, thymine and cytosine gave optically pure R enantiomers. In other cases, partial or complete racemization occurred. Optically pure ethyl (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoate (5a) was hydrolyzed to give (R)-3-(6-chloropurin-9-yl)-2-hydroxypropanoic acid (11). Reactions of 11 with various primary or secondary amines led to N6-substituted (R)-3-(adenin-9-yl)-2-hydroxypropanoic acids 14-19. Enantiomeric purity was determined from 1H NMR spectra measured in the presence of (-)-(R)-1-(9-anthryl)-2,2,2-trifluoroethan-1-ol.

Synthesis of Some 2'-C-Alkyl Derivatives of 9-(2-Phosphonomethoxyethyl)adenine and Related Compounds

1994 ◽  
Vol 59 (9) ◽  
pp. 2069-2094 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý ◽  
Ivan Rosenberg
Keyword(s):  
Reaction Pathway ◽  
Sodium Hydride ◽  
Amino Group ◽  
Trimethylsilyl Derivative ◽  
Phosphonic Acids ◽  
Alkyl Derivatives ◽  
Hydrolysis Of ◽  
Trifluoromethyl Derivative ◽  
Derivatives Of ◽  
Related Compounds

To study the effect of β-substitution in 2'-alkyl derivatives of 9-(2-phosphonomethoxyethyl)adenine (Ia) on the antiviral activity or group specificity, these derivatives were synthesized. 9-(2-Hydroxyalkyl)adenines VIII were prepared by alkylation of adenine with suitably substituted oxiranes XIII or 2-hydroxyalkyl p-toluenesulfonates IV and VI. After protection of the adenine amino group by benzoylation (compounds IX) or amidine formation (compounds X), the intermediates were alkylated with diisopropyl p-toluenesulfonyloxymethanephosphonate (XI) in the presence of sodium hydride. After deprotection, the obtained phosphonate diesters XII were converted into phosphonic acids I by transsilylation and hydrolysis. This synthetic scheme was used for the preparation of ethyl (Ie), propyl (If), 2-propyl (Ig), 2-methylpropyl (Ih), cyclopropyl (Ii), cyclohexyl (Ij), benzyl (Ik) and phenyl (Il) derivatives. The 2'-trifluoromethyl derivative XXIIa was prepared analogously from 9-(2-hydroxy-3,3,3-trifluoropropyl)adenine (XXa), obtained by alkylation of adenine sodium salt with 2-hydroxy-3,3,3-trifluoropropyl bromide. 2'-Trimethylsilyl derivative XIXa was obtained by alkylation of adenine with 2-diisopropylphosphonomethoxy-3-(4-toluenesulfonyloxy)propyltrimethylsilane (XVII) followed by transsilylation and hydrolysis of diester XVIIIa. 2,6-Diaminopurine derivatives XVIIId and XXIIb were obtained analogously. 9-(3-Phosphonomethoxybutyl)adenine (XXVIII) and 9-(2-methyl-2-phosphonomethoxypropyl)adenine (XXXV) were prepared from the corresponding hydroxy derivatives XXVIb and XXXII, respectively, by the same reaction pathway as derivatives I.

N-sec- and N-tert-Alkyl derivatives of methoxamine and related compounds

1968 ◽  
Vol 11 (4) ◽  
pp. 833-844 ◽  
Author(s):  
Richard Baltzly ◽  
Nariman B. Mehta
Keyword(s):  
Alkyl Derivatives ◽  
Derivatives Of ◽  
Related Compounds

scholarly journals Toward the Synthesis of the Fungal Metabolite (-)-TAN-2483B

2021 ◽  
Author(s):  
◽  
Daniel Phipps
Keyword(s):  
Biological Activity ◽  
Chemical Species ◽  
Ring System ◽  
Fungal Metabolites ◽  
Target Compound ◽  
Fungal Metabolite ◽  
Relative Configuration ◽  
Total Syntheses ◽  
Derivatives Of ◽  
Related Compounds

<p>In the search of chemical species with potential therapeutic biological activity, synthetic chemists have looked to nature for inspiration. Molecules built by biological machinery often have structures predisposed for biological interaction.  (-)-TAN-2483B and the related compounds (-)-TAN-2483A, and waol A are fungal metabolites that display biological activity in kinase inhibition and parathyroid-induced bone resorption. Though total syntheses of (-)-TAN-2483A and waol A have been achieved, the established methodology does not afford access to (-)-TAN-2483B owing to the unique relative configuration about the ring system.  Derivatives of D-galactal have been synthesised, and functionalised at the C-1 and C-2 positions, laying the groundwork for a route to (-)-TAN-2483B and analogues. Using D-galactal derivatives is advantageous as it circumvents some difficult transformations in the existing method for analogue synthesis.  The functionalities installed were halide and formyl groups at the C-2 position, and acetylenes at the C-1 position. The synthesis of 2-haloglycals from tri-O-acetyl-D-galactal using N-halosuccinimides was achieved in 32% and <37% for the bromo- and iodo- variants respectively. Vilsmeier-Haack formylation was explored using per-benzylated and per-acetylated galactals as substrates. Formylation of the per-benzylated species was achieved in 78% yield in accordance with literature values. Vilsmeier-Haack formylation on the per-acetylated galactal has not been reported and the glycal was found to be a poor substrate for the formylation. Theories regarding the incompatibility of the per-acetylated species with Vilsmeier-Haack conditions were developed.  Ferrier-type alkynylation of the 2-halo/formylglycals was explored, with yields up to 17% and 13% for the bromo- and iodo- species (unoptimised), and 7% for 2-formylglycal (after optimisation studies). The resulting 1-ethynyl-2-formyl/halo-2,3-unsaturated pyrans could be potential intermediates en route to the furanone ring of the target compound.</p>

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