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 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.

Purine Nucleoside Analogues. 11. An Alternative Synthesis of N- and O-Alkyl Derivatives of 9- and 7-[(2-Acetoxyethoxy)methyl]-N2-acetylguanine

1999 ◽  
Vol 64 (4) ◽  
pp. 685-695 ◽  
Author(s):  
Marina Madre ◽  
Natella Panchenko ◽  
Alexander Golbraikh ◽  
Regina Zhuk ◽  
Upendra K. Pandit ◽  
...  
Keyword(s):  
Nmr Spectra ◽  
Room Temperature ◽  
Purine Nucleoside ◽  
Nucleoside Analogues ◽  
Alternative Synthesis ◽  
Restricted Rotation ◽  
H Nmr ◽  
Alkyl Derivatives ◽  
Derivatives Of ◽  
Conformational Calculations

Alkylations of 9- and 7-[(2-acetoxyethoxy)methyl]-N2-acetylguanine with alkyl halogenides in the presence of base have been investigated affording a new route to the preparation of 1,N2-dimethyl- as well as O6-benzyl-9(7)-alkoxyalkylguanines. 1H NMR spectra revealed that the 1,N2-dimethyl derivatives exist as mixtures of two conformers at room temperature due to the restricted rotation about the C2-N2 bond. These findings agreed with conformational calculations.

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

ChemInform ◽  
2003 ◽  
Vol 34 (34) ◽  
Author(s):  
Marcela Krecmerova ◽  
Milos Budesinsky ◽  
Milena Masojidkova ◽  
Antonin Holy
Keyword(s):  
Optically Active ◽  
Alkyl Derivatives ◽  
Derivatives Of ◽  
Related Compounds

7-O-Alkyl derivatives of daunomycinone

1984 ◽  
Vol 49 (1) ◽  
pp. 313-319 ◽  
Author(s):  
Věra Přikrylová ◽  
Petr Sedmera ◽  
Josef V. Jizba ◽  
Jindřich Vokoun ◽  
Helena Lipavská ◽  
...  
Keyword(s):  
H Nmr ◽  
Toluenesulfonic Acid ◽  
Alkyl Derivatives ◽  
Derivatives Of

Reaction of daunomycinone (I) with alcohols and p-toluenesulfonic acid produces a mixture (~3 : 1) of its (7S)- and (7R)-O-alkyl derivatives II-IX. According to the 1H NMR evidence, the alicyclic ring exists in the 9H8 conformation in (7R)-O-alkyl derivatives, on the contrary to (7S)-epimers and 7-epi-daunomycinone that adopt the 8H9 conformation.

New Substituted Difurylchalcones

1992 ◽  
Vol 57 (10) ◽  
pp. 2203-2207 ◽  
Author(s):  
Katarína Špirková ◽  
Štefan Stankovský
Keyword(s):  
Nmr Spectra ◽  
Knoevenagel Condensation ◽  
Secondary Amines ◽  
H Nmr ◽  
Nucleophilic Reactions

Preparation of 1-(5-substituted-2-furyl)-2-phenylsulfonyl-2-furoyl ethylenes (IIa-IId) using the Lehnert modification of Knoevenagel condensation, as well as substitution nucleophilic reactions of the 1-(5-bromo-2-furoyl)-2-phenylsulfonyl-2-furoyl derivative (IIa) with the corresponding phenolate, thiophenolate and secondary amines are described. IR, UV and 1H NMR spectra of final products are presented.

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.

Photoreaktionen von Dekacarbonyldirhenium mit Allen und unverzweigten Allenderivaten / Photoreactions of Decacarbonyldirhenium with Allene and Unbranched Derivatives of Allene

1995 ◽  
Vol 50 (4) ◽  
pp. 649-660 ◽  
Author(s):  
Cornelius G. Kreiter ◽  
Wolfgang Michels ◽  
Gerhard Heeb
Keyword(s):  
Nmr Spectra ◽  
Crystal And Molecular Structure ◽  
Reaction Products ◽  
X Ray Diffraction ◽  
X Ray ◽  
H Nmr ◽  
Oxidative Rearrangement ◽  
Dirhenium Complexes ◽  
Derivatives Of ◽  
By Products

Decacarbonyldirhenium (1) reacts upon UV irradiation with allene (2), 1,2-butadiene (3) and 2,3-pentadiene (4) preferentially by CO substitution and oxidative rearrangement to the corresponding enneacarbonyl-μ-η1:3-endiyl-dirhenium complexes 5, 9, and 15 and to the octacarbonyl-μ-η2:2-allene-dirhenium complexes 6, the stereoisomers 10, 11, and 16. At elevated temperature 5, 9, and 15 loose CO and yield by a reductive rearrangement also the complexes 6, 10, 11, and 16. In addition to these main products, depending upon the allene derivative used, various by-products are obtained.By-products of the reaction o f 1 with 2 are octacarbonyl-μ-η3:3-(2,3-dimethylene-buta-1,4- diyl)dirhenium (7) and μ-η2:2-allene-hexacarbonyl-μ-η1:3-1-propene-1,3-diyl-dirheniurn (8). The photo reaction of 1 with 3 yields, in addition to 9-11, tetracarbonyl-η3-(E-5-ethylidene- 4-methyl-2-cyclopenten-1-yl)rhenium (12) and tetracarbonyl-η3-(Z-5-ethyliden-4- methyl-2-cyclopenten-1-yl)rhenium (13) as a mixture of isomers. 1 and 4 form the by-products tetracarbonyl-η3-(EZ-3-penten-2-yl)rhenium (17), tetracarbonyl-η3-(EE-3-penten-2-yl)rhenium (18) and heptacarbonyl-μ-η1:2:1:2-(4,5-dimethyl-2,6-octadiene-3,6-diyl)dirhenium (19) with an unusually bridging and chelating ligand. The constitutions of the reaction products have been concluded from the IR and 1H NMR spectra. For 19 the crystal and molecular structure has been determined by X-ray diffraction analysis.

Preparation of secondary alcohols of high optical purity

1986 ◽  
Vol 51 (2) ◽  
pp. 401-403 ◽  
Author(s):  
Otakar Červinka ◽  
Anna Fábryová ◽  
Irina Sablukova
Keyword(s):  
Nmr Spectroscopy ◽  
Optical Purity ◽  
Optically Active ◽  
Secondary Alcohols ◽  
Lithium Aluminium Hydride ◽  
Enantioselective Reduction ◽  
H Nmr ◽  
Lithium Aluminium ◽  
High Optical Purity ◽  
Optically Pure

Partially resolved enantiomers of optically active alcohols I-V, obtained by enantioselective reduction of the corresponding ketones with lithium aluminium hydride in the presence of (-)-quinine, were converted into crystalline 3,5-dinitrobenzoates or phenylcarbamates. The esters of the nearly optically pure enantiomers were separated by crystallization from the generally more soluble esters of the racemates. Optical purity of the hydrolytically liberated alcohols was determined by 1H NMR spectroscopy in the presence of chiral shifting agents.

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