Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA II. Racemic cis-Configured Derivatives

1996 ◽  
Vol 61 (5) ◽  
pp. 778-790 ◽  
Author(s):  
Radek Liboska ◽  
Milena Masojídková ◽  
Ivan Rosenberg
Keyword(s):  
Ring Opening ◽  
Nucleoside Analogs ◽  
Mitsunobu Reaction ◽  
Nucleotide Analogs ◽  
Heterocyclic Bases ◽  
Derivatives Of

Racemic N-(cis-2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of adenine- (6a, 6b), uracil- (6c) and cytosine- (6d) containing carbocyclic phosphonates is based on the reaction of cis-2-hydroxycycloalkyl derivatives of protected nucleobases with diisopropyl tosyloxymethanephosphonate. The starting purine-containing nucleoside analogs 5a-5f were prepared by the Mitsunobu reaction of protected nucleobases with trans-2-benzyloxycycloalkanols, whereas pyrimidine-containing nucleoside analogs 5g-5k were obtained by configurational inversion at C-2' of the corresponding 1-(trans-2-hydroxycycloalkyl)pyrimidines via ring opening of their 2,2'-anhydro derivatives.

Carbocyclic Phosphonate-Based Nucleotide Analogs Related to PMEA. I. Racemic trans-Configured Derivatives

1996 ◽  
Vol 61 (2) ◽  
pp. 313-332 ◽  
Author(s):  
Radek Liboska ◽  
Milena Masojídková ◽  
Ivan Rosenberg
Keyword(s):  
Ring Opening ◽  
Oxirane Ring ◽  
Nucleotide Analogs ◽  
Heterocyclic Bases ◽  
Derivatives Of

Racemic trans-N-(2-phosphonomethoxycycloalkyl) derivatives of heterocyclic bases, a novel type of nucleotide analogs related to 9-(2-phosphonomethoxyethyl)adenine (PMEA), are reported. The synthesis of fully protected adenine- (5), hypoxanthine- (7), guanine- (11), thymine- (13), uracil- (16) and cytosine-containing (18) carbocyclic nucleotide analogs is based on the reaction of trans-2-hydroxycycloalkyl derivatives of N-protected nucleobases (2, 10, 12, 14, 17) with diisopropyl tosyloxymethanephosphonate. Deprotection of these compounds afforded the title nucleotide analogs. The starting nucleoside derivatives have been prepared via nucleophilic oxirane ring opening of cycloalkene oxides with various protected or free nucleobases.

Derivatives of isatin in aqueous solution. I. Kinetics of ring opening of Isatin-5-sulfonate

1981 ◽  
Vol 34 (2) ◽  
pp. 365 ◽  
Author(s):  
H Stunzi
Keyword(s):  
Ring Opening ◽  
Rate Of Change ◽  
Spectroscopic Methods ◽  
Ph Values ◽  
Buffer Region ◽  
Pka Value ◽  
Back Titration ◽  
Kinetics Of ◽  
Derivatives Of ◽  
Sulfonate Anion

The reactions of isatin-5-sulfonate anion (si-) which cause a hysteresis in pH titrations were studied by pH-metric and n.m.r, spectroscopic methods. Rapid alkalimetric titrations [I 0.15 M (KNO3),37�] gave the pKa value corresponding to the addition of OH- to si- [pKa(ring) 9.55]. The slow ring opening to the sulfonatoisatate dianion (sia2-) led to a drift of the pH values towards an equilibrium buffer region. Its pKa, value [pKa(eq) 3.44] corresponds to the reaction si-+H2O ↔ sia 2-+H+ Rapid back-titration gave the pKa value of the ring-opened species Hsia- [pKa(open) c. 1.3]. The rate law for the ring opening d[sia]/dt=k2 [siOH](OH)+k1*[si] was obtained from the rate of change of pH. N-Methylisatin-5-sulfonate behaves analogously.

Preparation of 2,3-Dideoxy-2,3-epimino and 3,4-Dideoxy-3,4-epimino Derivatives of 1,6-Anhydro-β-D-hexopyranoses by Mitsunobu Reaction

1998 ◽  
Vol 63 (6) ◽  
pp. 813-825 ◽  
Author(s):  
Jiří Kroutil ◽  
Tomáš Trnka ◽  
Miloš Buděšínský ◽  
Miloslav Černý
Keyword(s):  
Nmr Spectra ◽  
Mitsunobu Reaction ◽  
Derivatives Of ◽  
C Nmr

A series of new 2-, 3- and 4-benzylamino-2-, 3- and 4-deoxy derivatives of 1,6-anhydro-β-D-hexopyranoses were prepared from 1,6:2,3- and 1,6:3,4-dianhydro-β-D-hexopyranoses by treatment with benzylamine and converted into 2,3-(N-benzylepimino)-2,3-dideoxy- and 3,4-(N-benzylepimino)-3,4-dideoxy-β-D-hexopyranoses of the D-allo, D-galacto and D-talo configuration by Mitsunobu reaction. The structures of benzylamino and benzylimino derivatives were confirmed by 1H and 13C NMR spectra.

scholarly journals Biochemical Studies on the Mechanism of Human Immunodeficiency Virus Type 1 Reverse Transcriptase Resistance to 1-(β-d-Dioxolane)Thymine Triphosphate

2007 ◽  
Vol 51 (6) ◽  
pp. 2078-2084 ◽  
Author(s):  
Johan Lennerstrand ◽  
Chung K. Chu ◽  
Raymond F. Schinazi
Keyword(s):  
Human Immunodeficiency Virus ◽  
Reverse Transcriptase ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Nucleoside Analogs ◽  
Nucleotide Analogs ◽  
Immunodeficiency Virus ◽  
Large Panel ◽  
Tenofovir Diphosphate

ABSTRACT A large panel of drug-resistant mutants of human immunodeficiency virus type 1 reverse transcriptase (RT) was used to study the mechanisms of resistance to 1-(β-d-dioxolane)thymine triphosphate (DOT-TP) and other nucleotide analogs. RT containing thymidine analog-associated mutations (TAM) or RT with a T69S-SG insertion in combination with TAM removed 3′-azido-3′-deoxythymidine-5′-monophosphate or tenofovir more efficiently than DOT-monophosphate from chain-terminated DNA primer/template through ATP-mediated pyrophosphorolysis. For non-ATP-dependent discrimination toward DOT-TP, high levels of resistance were found for RT bearing the Q151M mutation with family mutations, while RT bearing only the M184V or the Y115F mutation conferred no resistance to DOT-TP. A lower degree of resistance to DOT-TP than to tenofovir diphosphate or carbovir-TP was found for RT containing the K65R mutation. In the present studies, 1-(β-d-dioxolane)guanine triphosphate, another nucleotide with a dioxolane sugar moiety, showed a resistance profile similar to that of DOT-TP. The results suggest that DOT, compared with other approved nucleoside analogs, is overall more resilient to mutations such as TAM, M184V, and K65R, which are commonly found in viruses derived from subjects failing multinucleoside therapy.

Synthesis and Biological Effects of N-(2-Phosphonomethoxyethyl) Derivatives of Deazapurine Bases

1993 ◽  
Vol 58 (6) ◽  
pp. 1419-1429 ◽  
Author(s):  
Hana Dvořáková ◽  
Antonín Holý
Keyword(s):  
Biological Effects ◽  
Sodium Hydride ◽  
Cesium Carbonate ◽  
Cytostatic Effect ◽  
Phosphonic Acids ◽  
Dna Viruses ◽  
Purine Bases ◽  
Heterocyclic Bases ◽  
L 1210 Leukemia ◽  
Derivatives Of

Analogs of antiviral 9-(2-phosphonomethoxyethyl)adenine (PMEA,II), containing modified purine bases 1-deazaadenine (VII, 3-deazapurine (XI), 7-deaza-7-cyanoadenine (XIIIb) and 3-deazaguanine (XXIb) were prepared by alkylation of the heterocyclic bases with bis(2-propyl) 2-chloroethoxymethylphosphonate (V) in dimethylformamide in the presence of sodium hydride or cesium carbonate. The obtained protected derivatives were deblocked with bromotrimethylsilane to give the phosphonic acids. 3-DeazaPMEG (XXIb) is active against DNA viruses and exhibits a marked cytostatic effect against L-1210 leukemia.

scholarly journals Fates of imine intermediates in radical cyclizations of N-sulfonylindoles and ene-sulfonamides

2015 ◽  
Vol 11 ◽  
pp. 1649-1655 ◽  
Author(s):  
Hanmo Zhang ◽  
E Ben Hay ◽  
Stephen J Geib ◽  
Dennis P Curran
Keyword(s):  
Carbonyl Group ◽  
Ring Opening ◽  
Radical Cyclizations ◽  
Type Reaction ◽  
Primary Products ◽  
Lactam Carbonyl Group ◽  
Lactam Carbonyl ◽  
Imine Reduction ◽  
Derivatives Of

Two new fates of imine intermediates formed on radical cyclizations of ene-sulfonamides have been identified, reduction and hydration/fragmentation. Tin hydride-mediated cyclizations of 2-halo-N-(3-methyl-N-sulfonylindole)anilines provide spiro[indoline-3,3'-indolones] or spiro-3,3'-biindolines (derived from imine reduction), depending on the indole C2 substituent. Cyclizations of 2-haloanilide derivatives of 3-carboxy-N-sulfonyl-2,3-dihydropyrroles also presumably form spiro-imines as primary products. However, the lactam carbonyl group facilitates the ring-opening of these cyclic imines by a new pathway of hydration and retro-Claisen-type reaction, providing rearranged 2-(2'-formamidoethyl)oxindoles.

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