xDNA: A New Genetic System?

Professor Eric Kool and his co-workers have developed " eXpanded DNA " dubbed "xDNA". The synthetic xDNA is expanding by adding benzene molecule to the base on the nucleotides and is a bit longer than the regular 'B' form.


Unlike natural DNA, the expanded DNA is fluorescent and is considerably more stable when subjected to higher temperatures. Its unusual fluorescent properties could make it useful as a probe or diagnostic marker.

Is xDNA also capable of replicating? That is something Kool hopes to find out. Experiments with xDNA are expected to provide new insight into the behavior of natural DNA.

Ref: E. Kool, et al. Angew. Chem Int. Ed., 44, 3118-3122 (2005), JACS , 128, 9219-9230 (2006).

The solvent makes the difference

The solvent surrounding the chiral molecule creates a chiral shell (Chiral Imprint). The chiroptical properties can originate mainly from the chiral solvent shell rather than from the chiral solute. For example, (S)-methyloxirane has a positive optical rotation in water but has a relatively strong negative value in benzene (P. Mukhopadhyay et al. Angew Chem Int Ed 2007, 46, 6450-6452).

 

Computational experiments by J Neugebauer (Angew Chem Int Ed 2007, 46, 7738-7740) shows the presence of the solute imprints a chiral structure on the inner solvation shell.

Cyanation of aryl halides

There are several methods available for the cyanation of aryl halides. However, a common problem with many of the more traditional methods is that they are very toxic# One method to full fill these criteria has been around for a while (Weissman S A et al., J. Org. Chem.2005, 70, 1508-1510.)

  Figure: Ligand-free, palladium-catalyzed cyanation of aryl halides. 

Potassium hexacyanoferrate(II) has been used as a cyanide source. This result increases the list of metal-catalyzed reactions that can be performed without ligand.

This method's advantage is obvious; in contrast to other cyanating agents, potassium hexacyanoferrate(II) is less poisonous# and can be handle without special precaution due to the slow release of cyanide ions. Additionally, it significantly improved catalytic productivity compared to know procedures achieved previously.

#( KCN is extremely toxic (LDL0(oral, human) =2.86mg Kg-1 and develop HCN on contract with acidic water. K4[Fe(CN)6]­ is non-toxic and used in the food industry for metal precipitation in wine. Also, it has been used as an anti-agglutinating auxiliary for NaCl (table salt). It is soluble in water without decomposition. Schareina T et al, Chem Commun., 2004, 1388-1389.)

Myers Asymmetric Alkylation

Psuedoephedrine is a chiral auxiliary used for the synthesis of enantiomerically enriched carboxylic acid, aldehyde, alcohol and ketones.

Both enantiomers of pseudoephedrine are inexpensive and can be N-acylated in high yields to generate its tertiary amides. In the presence of lithium chloride, the enolates of the corresponding pseudoephedrine amides undergo diastereoselective alkylations with a wide range of alkyl halides.

Advantages of using pseudoephedrine as chiral auxiliary,

• Enolate of pseudoephedrine amide undergoes efficient and high diastereoselective alkylation with a wide variety of alkyl halides,

• High enantiomerically enriched carboxylic acids, alcohols, aldehydes, and ketones, and

• Large scale/ Preocess application ( low cost of the auxiliary, the crystallinity of starting materials and products, no requirement of carcinogenic solvents.) 

Ref: Myers, A.G. et al., J. Am. Chem. Soc., 1997, 119, 6496.

Racemic Switch

A racemic switch or chiral switch is the redevelopment in the single-enantiomer form of a drug that was first approved as a racemates (racemic mixture). Sometimes, the pharmaceutical activity of a racemic mixture is present only in one enantiomer, and the other is inactive, or the other enantiomer has an undesired activity from the first.

Omeprazole

For exmaple, Omeprazole is an Antiulcer drug (AstraZeneca) marketed in the U.S. as a racemic drug in 1995. It s a racemic mixture of R-omeprazole and S-omeprazole. Since its patent ran out in 2002 and the pharmacological activity lies in (S)-enantiomer, the company has patented now (S)-omeprazole named as esomeprazole.

Reduction of amino acids

There are many ways to reduce amino acids to amino alcohols; using sodium borohydride and iodine in THF is an excellent process. This methodology is not only nonexpensive and safety perspective, but the workup is much easier (compared to LiAlH4).

Iodine oxidizes the hydride giving a mole of H2 and generating BH3 in situ. All that borane actually the stuff that reduces the acid to alcohol.

Organic Synthesis: Problems

Here are some links to the best organic synthesis problems on the web (some even supply answers) 

Tohru Fukuyama's Group: http://www.f.u-tokyo.ac.jp/~fukuyama/index-e.htm 

Steven Ley's Group: http://leygroup.ch.cam.ac.uk/Education/education.htm 

David Evan's Group: http://daecr1.chem.harvard.edu/problems/