scholarly journals Chemical and chemoenzymatic routes to bridged homoarabinofuranosylpyrimidines: Bicyclic AZT analogues

2022 ◽  
Vol 18 ◽  
pp. 95-101
Author(s):  
Sandeep Kumar ◽  
Jyotirmoy Maity ◽  
Banty Kumar ◽  
Sumit Kumar ◽  
Ashok K Prasad
Keyword(s):  
Hydroxy Group ◽  
Chemical Method ◽  
Secondary Hydroxy Group ◽  
Synthetic Pathway ◽  
Conformationally Restricted ◽  
Hydroxy Groups ◽  
Azt Analogues

Conformationally restricted diastereomeric homoarabinofuranosylpyrimidines (AZT analogue), i.e., (5′R)-3′-azido-3′-deoxy-2′-O,5′-C-bridged-β-ᴅ-homoarabinofuranosylthymine and -uracil had been synthesized starting from diacetone ᴅ-glucofuranose following chemoenzymatic and chemical routes in 34–35% and 24–25% overall yields, respectively. The quantitative and diastereoselective acetylation of primary hydroxy over two secondary hydroxy groups present in the key nucleoside precursor was mediated with Lipozyme® TL IM in 2-methyltetrahydrofuran following a chemoenzymatic pathway. Whereas, the protection of the primary hydroxy over the lone secondary hydroxy group in the key azido sugar precursor was achieved using bulky tert-butyldiphenylsilyl chloride (TBDPS-Cl) in pyridine in 92% yield following a chemical synthetic pathway. The chemoenzymatic method was found to be superior over the chemical method in respect of the number of synthetic steps and overall yield of the final product.

Participation of the oxygen-containing substituent in alkaline saponification of 3,4a-disubstituted 4,4-dimethyl-5,6β-epoxy-A-homo-5β-cholestane derivatives

1986 ◽  
Vol 51 (4) ◽  
pp. 930-936 ◽  
Author(s):  
Helena Velgová
Keyword(s):  
Hydroxy Group ◽  
Acetoxy Group ◽  
Epoxide Ring ◽  
Main Component ◽  
Hydroxy Groups

Alkaline saponification of the 3-acetoxy group in 3,4a-disubstituted 4,4-dimethyl-5,6β-epoxy-A-homo-5βcholestane derivatives I-VI was studied. It was found that the 3α- and 4aα-hydroxy groups participated in the cleavage of the 5β,6β-epoxide ring in the derivatives II-IV: the 5(O)n participation by the 3α-hydroxy group (the derivatives III and IV) led to formation of the transannular 3α,5α-epoxides XII and XIV whereas the participation by the 4aα-hydroxy group (the derivatives II and IV) gave rise to the 4aα,5α-epoxides IX and XV. The 5(O)n participation by the 3α-hydroxy group predominated over the preparation by the 4aα-hydroxy group. In the case of the 4a-keto epoxides V and VI the retroaldol-aldol type isomerization led to formation of 3β-hydroxy-4,4-dimethyl-5,6β-epoxy-A-homo-5β-cholestan-4a-one as the main component of the equilibration mixtures.

scholarly journals Linking Aromatic Hydroxy Metabolic Functionalization of Drug Molecules to Structure and Pharmacologic Activity

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2119 ◽  
Author(s):  
Babiker El-Haj ◽  
Samrein Ahmed ◽  
Mousa Garawi ◽  
Heyam Ali
Keyword(s):  
Benzene Ring ◽  
Hydroxy Group ◽  
Water Solubility ◽  
Parent Drug ◽  
Drug Action ◽  
Alkoxy Group ◽  
Drug Molecules ◽  
Drug Classes ◽  
Pharmacologic Activity ◽  
Hydroxy Groups

Drug functionalization through the formation of hydrophilic groups is the norm in the phase I metabolism of drugs for the modification of drug action. The reactions involved are mainly oxidative, catalyzed mostly by cytochrome P450 (CYP) isoenzymes. The benzene ring, whether phenyl or fused with other rings, is the most common hydrophobic pharmacophoric moiety in drug molecules. On the other hand, the alkoxy group (mainly methoxy) bonded to the benzene ring assumes an important and sometimes essential pharmacophoric status in some drug classes. Upon metabolic oxidation, both moieties, i.e., the benzene ring and the alkoxy group, produce hydroxy groups; the products are arenolic in nature. Through a pharmacokinetic effect, the hydroxy group enhances the water solubility and elimination of the metabolite with the consequent termination of drug action. However, through hydrogen bonding, the hydroxy group may modify the pharmacodynamics of the interaction of the metabolite with the site of parent drug action (i.e., the receptor). Accordingly, the expected pharmacologic outcome will be enhancement, retention, attenuation, or loss of activity of the metabolite relative to the parent drug. All the above issues are presented and discussed in this review using selected members of different classes of drugs with inferences regarding mechanisms, drug design, and drug development.

scholarly journals Crystal structure oftrans-N,N′-bis(3,5-di-tert-butyl-2-hydroxyphenyl)oxamide methanol monosolvate

2016 ◽  
Vol 72 (7) ◽  
pp. 918-921
Author(s):  
Miguel-Ángel Velázquez-Carmona ◽  
Sylvain Bernès ◽  
Francisco Javier Ríos-Merino ◽  
Yasmi Reyes Ortega
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bonds ◽  
Hydroxy Group ◽  
Molecular Conformation ◽  
Methanol Molecule ◽  
Molecular Symmetry ◽  
Methyl Group ◽  
Supramolecular Motifs ◽  
Butyl Group ◽  
Hydroxy Groups

The here crystallized oxamide was previously characterized as an unsolvated species [Jímenez-Pérezet al.(2000).J. Organomet. Chem.614–615, 283–293], and is now reported with methanol as a solvent of crystallization, C30H44N2O4·CH3OH, in a different space group. The introduction of the solvent influences neither the molecular symmetry of the oxamide, which remains centrosymmetric, nor the molecular conformation. However, the unsolvated molecule crystallized as an ordered system, while many parts of the solvated crystal are disordered. The hydroxy group in the oxamide is disordered over two chemically equivalent positions, with occupancies 0.696 (4):0.304 (4); onetert-butyl group is disordered by rotation about the C—C bond, and was modelled with three sites for each methyl group, each one with occupancy 1/3. Finally, the methanol solvent, which lies on a twofold axis, is disordered by symmetry. The disorder affecting hydroxy groups and the solvent of crystallization allows the formation of numerous supramolecular motifs using four hydrogen bonds, with N—H and O—H groups as donors and the oxamide and methanol molecule as acceptors.

Preparation and Conformational Study of B-Ring Substituted Lupane Derivatives

2006 ◽  
Vol 71 (8) ◽  
pp. 1131-1160 ◽  
Author(s):  
Martin Dračínský ◽  
Simona Hybelbauerová ◽  
Jan Sejbal ◽  
Miloš Buděšínský
Keyword(s):  
Double Bond ◽  
Hydroxy Group ◽  
Molecular Modelling ◽  
Nmr Spectra ◽  
Hydroxy Derivative ◽  
Secondary Hydroxy Group ◽  
Conformational Study ◽  
Primary Hydroxy Group ◽  
Type 3 ◽  
C Nmr

New lupane-type triterpenoids with 5(6) double bond were prepared using the method of partial demethylation on carbon C-4. Hydroboration of the double bond led to 6α-hydroxy derivative. By the oxidation and following reduction of 6α-hydroxy derivative the 6-oxo and 6β-hydroxy derivatives were prepared. A new method for selective oxidation of secondary hydroxy group in the presence of primary hydroxy group was performed. The conformation of ring A of new lupane-type 3-oxo derivatives with a substituent on ring B was elucidated on the bases of 1H and 13C NMR spectra and molecular modelling.

scholarly journals Threefold helical assembly via hydroxy hydrogen bonds: the 2:1 co-crystal of bicyclo[3.3.0]octane-endo-3,endo-7-diol and bicyclo[3.3.0]octane-endo-3,exo-7-diol

2021 ◽  
Vol 77 (3) ◽  
pp. 270-276
Author(s):  
Isa Y. H. Chan ◽  
Mohan M. Bhadbhade ◽  
Roger Bishop
Keyword(s):  
Crystal Structure ◽  
Hydrogen Bond ◽  
Hydrogen Bonding ◽  
Hydrogen Bonds ◽  
Hydroxy Group ◽  
Network Structure ◽  
General Position ◽  
Three Dimensional ◽  
Screw Axis ◽  
Hydroxy Groups

Reduction of bicyclo[3.3.0]octane-3,7-dione yields a mixture of the endo-3,endo-7-diol and endo-3, exo-7-diol (C8H14O2) isomers (5 and 6). These form (5)2·(6) co-crystals in the monoclinic P21/n space group (with Z = 6, Z′ = 1.5) rather than undergoing separation by means of fractional recrystallization or column chromatography. The molecule of 5 occupies a general position, whereas the molecule of 6 is disordered over two orientations across a centre of symmetry with occupancies of 0.463 (2) and 0.037 (2). Individual diol hydroxy groups associate around a pseudo-threefold screw axis by means of hydrogen bonding. The second hydroxy group of each diol behaves in a similar manner, generating a three-dimensional hydrogen-bonded network structure. This hydrogen-bond connectivity is identical to that present in three known helical tubuland diol–hydroquinone co-crystals, and the new crystal structure is even more similar to two homologous aliphatic diol co-crystals.

scholarly journals Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

2020 ◽  
Vol 16 ◽  
pp. 2854-2861
Author(s):  
Jennifer Frommer ◽  
Sabine Müller
Keyword(s):  
Building Block ◽  
Rna Structure ◽  
Building Blocks ◽  
Structure And Function ◽  
Lessons Learned ◽  
Modified Oligonucleotides ◽  
Synthetic Pathway ◽  
Protection Scheme ◽  
And Function ◽  
Hydroxy Groups

Synthesis of site-specifically modified oligonucleotides has become a major tool for RNA structure and function studies. Reporter groups or specific functional entities are required to be attached at a pre-defined site of the oligomer. An attractive strategy is the incorporation of suitably functionalized building blocks that allow post-synthetic conjugation of the desired moiety. A C8-alkynyl-modified adenosine derivative was synthesized, reviving an old synthetic pathway for iodination of purine nucleobases. Silylation of the C8-alkynyl-modified adenosine revealed unexpected selectivity of the two secondary sugar hydroxy groups, with the 3'-O-isomer being preferentially formed. Optimization of the protection scheme lead to a new and economic route to the desired C8-alkynylated building block and its incorporation in RNA.

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