Synthesis of Enantiomerically Pure Nucleosides and Gene Chip

The design and synthesis of nucleoside analogues as potential anticancer and antiviral agents have emerged as a very dynamic field of research. The core objective of this intense research is amendment in sugar and base moieties to make the nucleoside more apt for therapeutic response. Enantiomers of a particular compound sometimes show opposite or entirely different types of bioactivity. Here, synthesis of large variety of nucleoside has been presented in enantiomerically pure form by judicious manipulation of cheapest possible chiral pool of D-glucose. Intramolecular nitrone cycloaddition (INC) and ring closing metathesis (RCM) has been used as the main synthetic tool besides commonly used protection deprotection and C-C bond cleavage reaction.
Nu. B. O n* * m N HO N N NH2 N N N NH2 N N OH HO O OH N HO OH N N OH Spiro N N HO Oxepano N OH HO Locked HO O OH O OH (-) Carbovir N N N O NH NH2 OH N N N NH2 N N NH2

Bicyclic ethers N N HO HO HO H N H OH N N HO HO N H H H O OH N NH2 HO N N N NH2 N N NH2 N NH2 HO HO OH Carbocyclic OH

D-Glucose
O

DNA chip is a high density array of short single stranded DNA molecules bound to a solid surface which can recognize complementary stranded DNA for use in probing a biological sample to determine gene expression, marker pattern or nucleotide sequence of DNA/RNA. Preparation of an efficient photo-removable protecting group is an important and active area of research for photolithographic fabrication of high-density DNA microarray. Nucleoside monomers protected with photo-removable protecting group used for stepwise synthesis of oligonucleotide on glass plate. As the process is stepwise and involves large number of cyclical steps, almost complete photo deprotection in each step is essential for fabrication of high density microarray. Again, the sensitivity of DNA to ultraviolet radiation limits the range of wavelengths usable for the photolitographic steps to mainly 366 nm. Therefore, the choice of photo-removable hydroxyl protecting groups depends on the efficiency and rate of photo deprotection at that wavelength. The rate of deprotection, is a function of the molar absorptivity of the chromophore at the wavelength of irradiation and the quantum yield of the desired
X R1 R hR O R
1

O R

R = Ph, C6F5,C6H5OCH3 R1 = Ph, OMe, Br B O O B O X= O O O OH OH

photochemical product formation process. So, an efficient protecting group for DNA microarray must have the following characteristics - i) the absorbance should be high at 366 nm, ii) quantum yield should be high iii) it should be completely removable even in absence of solvent. Commercially used photo removable protecting groups (NVoc or MeNPoc) have several limitations in this respect. Here I have presented some benzophenone based protecting group which showed good photo reactivity but need further modification to be good enough for using in fabrication of gene chip.