5'-O-[Bis(4-methoxyphenyl)phenylmethyl]-2'-deoxy-N-[(dimethylamino)methylene]guanosine 3'-[2-cyanoethyl bis(1-methylethyl)phosphoramidite]
[CAS 330628-04-1]

Identification

• Classification: Biochemical >> Nucleoside drugs >> Deoxynucleotides and their analogues
• Name: 5'-O-[Bis(4-methoxyphenyl)phenylmethyl]-2'-deoxy-N-[(dimethylamino)methylene]guanosine 3'-[2-cyanoethyl bis(1-methylethyl)phosphoramidite]
• Synonyms: DMT-dG(dmf) Phosphoramidite; N'-[9-[(2R,4S,5R)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-4-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxyoxolan-2-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylmethanimidamide
• Molecular Formula: C₄₃H₅₃N₈O₇P
• Molecular Weight: 824.90
• CAS Registry Number: 330628-04-1
• SMILES: CC(C)N(C(C)C)P(OCCC#N)O[C@H]1C[C@@H](O[C@@H]1COC(C2=CC=CC=C2)(C3=CC=C(C=C3)OC)C4=CC=C(C=C4)OC)N5C=NC6=C5N=C(NC6=O)/N=C/N(C)C

Properties

• Solubility: Insoluble (9.1E^-5 g/L) (25 °C), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2015 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P280-P301+P312-P302+P352-P305+P351+P338

chemBlink Chemical Story

5'-O-[Bis(4-methoxyphenyl)phenylmethyl]-2'-deoxy-N-[(dimethylamino)methylene]guanosine 3'-[2-cyanoethyl bis(1-methylethyl)phosphoramidite] is a protected guanosine phosphoramidite derivative used as a chemical building block in the synthesis of DNA oligonucleotides. It belongs to the class of nucleoside phosphoramidites developed for automated solid-phase DNA synthesis, where individual protected nucleosides are sequentially coupled to construct defined DNA sequences.

The development of nucleoside phosphoramidite chemistry was a major advance in synthetic biology and molecular biology. Earlier methods for constructing oligonucleotides were limited by reaction efficiency and required lengthy procedures. The introduction of phosphoramidite-based synthesis provided a practical method for automated DNA assembly by allowing rapid and controlled formation of internucleotide phosphate linkages. Protected derivatives of guanosine, including compounds of this type, were developed to overcome the chemical reactivity of nucleobases and hydroxyl groups during synthesis.

The compound is derived from 2'-deoxyguanosine, one of the four naturally occurring deoxyribonucleosides found in DNA. The molecule contains a guanine nucleobase attached to a deoxyribose sugar through a beta-N-glycosidic bond. The guanine base contains multiple nitrogen and oxygen atoms that participate in hydrogen bonding in natural DNA and therefore require protection during chemical synthesis.

The exocyclic amino group of guanine is protected with a dimethylaminomethylene group. This protecting group converts the amino functionality into a less reactive derivative, preventing unwanted side reactions during oligonucleotide assembly. Protection of guanine is essential because unprotected nucleobase functional groups can interfere with phosphoramidite coupling reactions and reduce synthesis efficiency.

The 5'-hydroxyl group of the deoxyribose sugar is protected with a bis(4-methoxyphenyl)phenylmethyl group, commonly known as a dimethoxytrityl-type protecting group. This bulky aromatic protecting group temporarily blocks the 5'-position during synthesis. It can be selectively removed under acidic conditions, exposing the hydroxyl group for the next nucleotide coupling cycle while leaving other protecting groups intact.

The 3'-position of the sugar is converted into a phosphoramidite functionality. This phosphorus-containing group is the key reactive component that enables incorporation of the nucleoside into a growing DNA chain. The phosphoramidite contains a phosphorus(III) center bonded to the nucleoside oxygen, a 2-cyanoethyl protecting group, and a diisopropylamino-type leaving group.

During automated DNA synthesis, the phosphoramidite group is activated by a suitable activator and reacts with the free 5'-hydroxyl group of the growing oligonucleotide chain. This coupling reaction forms a phosphite triester linkage. The newly formed phosphorus(III) linkage is then oxidized to generate the stable phosphate backbone found in DNA.

The 2-cyanoethyl group attached to phosphorus serves as a protecting group for the phosphate functionality. It remains stable during nucleotide coupling cycles and is removed during the final deprotection process. This controlled protection strategy allows multiple synthesis cycles to occur without damaging the growing oligonucleotide chain.

The aromatic protecting groups contribute significant hydrophobic character, while the nucleoside and phosphoramidite portions provide polar functionality. The compound is designed to be compatible with the organic solvents and anhydrous conditions used in automated oligonucleotide synthesizers. Because phosphoramidites are sensitive to moisture, they are handled under dry conditions to prevent hydrolysis and loss of reactivity.

The primary application of this guanosine phosphoramidite derivative is the preparation of synthetic DNA molecules used in molecular biology, biotechnology, and biomedical research. It enables the incorporation of guanine residues into custom-designed oligonucleotides used for applications such as genetic analysis, molecular cloning, sequencing technologies, and nucleic acid research.

Overall, 5'-O-[Bis(4-methoxyphenyl)phenylmethyl]-2'-deoxy-N-[(dimethylamino)methylene]guanosine 3'-[2-cyanoethyl bis(1-methylethyl)phosphoramidite] is a protected guanosine building block developed for automated DNA synthesis. Its carefully selected protecting groups allow selective chemical reactions at specific positions of the nucleoside, enabling efficient and reliable construction of synthetic DNA sequences.