8-BROMOADENOSINE

8-BROMOADENOSINE Property

Melting point:

210-212 °C (dec.)(lit.)

Boiling point:

717.7±70.0 °C(Predicted)

Density 

1.8171 (rough estimate)

refractive index 

1.6400 (estimate)

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

solubility 

DMSO (Slightly), Methanol (Slightly, Sonicated)

pka

12.89±0.70(Predicted)

form 

powder

color 

white

Water Solubility 

Soluble in DMSO, and DMF. Insoluble in water.

Sensitive 

Air Sensitive

BRN 

627737

CAS DataBase Reference

2946-39-6(CAS DataBase Reference)

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36-24/25-22

WGK Germany 

3

F 

10-23

HS Code 

2934 99 90

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P302+P352IF ON SKIN: wash with plenty of soap and water.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

8-BROMOADENOSINE Chemical Properties,Usage,Production

Description

8-Bromoadenosine is a nucleotide that is structurally related to adenosine. It can be used as an inhibitor of guanine nucleotide-binding proteins and has shown biological properties in vitro. 8-Bromoadenosine has been shown to inhibit the mitochondrial membrane potential, cytosolic Ca2+, and the synthesis of RNA and protein. 8-Bromoadenosine also inhibits leukemia inhibitory factor (LIF) production by 3T3-L1 preadipocytes and induces apoptosis in T84 cells.

Chemical Properties

Off-White Solid

Uses

8-Bromoadenosine is an adenosine binding inhibitor. formation of 8-S-L-cysteinyladenosine from 8-Bromoadenosine and cysteine.

Definition

ChEBI: 8-Bromoadenosine is a purine nucleoside.

Synthesis

The general procedure for the synthesis of (2R,3R,4S,5R)-2-(6-amino-8-bromo-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol from (2R,3R,4S,5R)-2-(6-amino-8-bromo-9H-purin-9-yl)-5-(hydroxymethyl)tetrahydrofuran-3,4-diol is as follows: embodiment 1: the modified The synthesis of siRNA molecules involves the preparation of 8-methoxyadenosine phosphoramidite and its incorporation in the antisense chain of cystatinase 2 siRNA. FIG. 7A illustrates the structure of double-stranded positive control siRNAs (SEQ ID NO:20 (upper strand) and SEQ ID NO:21 (lower strand)) versus double-stranded negative control siRNAs (SEQ ID NO:22 (upper strand) and SEQ ID NO:23 (lower strand)). FIG. 7B illustrates a schematic representation of individually modified siRNAs, wherein the modifications include, but are not limited to, 8-malonylideneoxyadenosine, 8-phenylethoxyadenosine, and 8-cyclohexylethoxyadenosine. In FIG. 7B, 4AS corresponds to SEQ ID NO:24, 6AS corresponds to SEQ ID NO:25, 10AS corresponds to SEQ ID NO:26, and 15AS corresponds to SEQ ID NO:27. Bromination reactions of adenosine have been reported in the field of chemistry; typically, yields of 8-bromoadenosine ranging from about 75% to about 82.5% are obtained using a fourfold excess of bromine. During the synthesis of nucleo-phosphoramidites, the 5'-OH of N'-benzoyl adenosine was first protected in order to protect the 2'-OH group. Subsequently, 2'-OH was protected using tert-butyldimethylsilyl chloride (TBDMS-Cl).Although the addition of Ag+ ions helped to reduce the unwanted reaction of 3'-OH, side reactions usually still occurred, leading to a significant decrease in the overall yield. Therefore, in order to increase the overall yield, a novel protecting group, dibutylmethylsilyl disilicate (DTBSDT), was employed, which protects both 5'-OH and 3'-OH and makes 2'-OH easily protected by TBDMS-Cl. The two reactions are essentially one-pot reactions, avoiding cumbersome separation steps. The reaction was nearly quantitative and the product yield was about 96% to 98% (see Figures 3 and 4). In methanol, the methoxy derivatives were synthesized using sodium methanol reagents to give 8-methoxyadenosine derivatives and 8-oxoadenosine derivatives. The isolation of these two derivatives was more complicated and the yield of the desired compounds was less than 50%. Therefore, by reacting n-BuLi with an excess of anhydrous methanol to generate the methoxy anion in situ, the reaction is much more efficient, with yields of about 85% to 93% of the desired product. Deprotection of 5'-OH and 3'-OH was accomplished at subzero temperature using a special fluoride reagent, HF-pyridine. The product yields of these DMT reactions were low, about 40% to 50%. The product yield of the phosphoramidite synthesis step was about 95% to 98%. Subsequently, 8-methoxyadenosine phosphoramidite is doped into positions 9 or 14 of the antisense chain (corresponding to positions 11 and 6 of the sense chain, respectively), or both positions 9 and 14. The propargyl portion of adenosine at position 8 simplifies the synthesis of other 8-substituted adenosine analogs. The propargyl portion of 8-alkynyl adenosine in the siRNA can be reacted with a suitable water-soluble azide via a "click" reaction to form the desired minor groove modification.

References

[1] Journal of Organic Chemistry, 2014, vol. 79, # 21, p. 9992 - 9997
[2] European Journal of Organic Chemistry, 2009, # 10, p. 1515 - 1521
[3] Patent: WO2011/119674, 2011, A1. Location in patent: Page/Page column 50-51
[4] Journal of the American Chemical Society, 2012, vol. 134, # 42, p. 17643 - 17652
[5] Synthesis, 2004, # 17, p. 2799 - 2804