Citation Page

Original Source (cited by our article): (10) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277-7287.

1.   Sorensen, A. M.; Nielsen, K. E.; Vogg, B.; et al Tetrahedron. 2001, 57, 10191-10201.

Synthesis and NMR-studies of dinucleotides with conformationally restricted cyclic phosphotriester linkages 

Dess-Martin periodinane oxidation step[1]
 

The easily available, protected, thymidine derivative 1 was oxidized using the Dess�Martin periodinane oxidation and used in a Grignard reaction, with the application of a commercial solution of vinyl magnesium bromide. This reaction yielded isomers 2 and 3 in an equimolar ratio, but in a relatively low yield (41%) (33% yield over the two steps). The product was isolated as a clear oil and as a 1:1 mixture of epimers. The yield was 620 mg, 41%. Other Grignard reactions that have been performed on the same aldehyde have reported similar low percent yields, especially due to a reductive side-reaction resulting in the starting material. As an alternative to the vinyl Grignard reaction above, the use of an acetylenic Grignard reagent followed by a reduction reaction using the Lindlar catalyst was applied. Therefore, the Grignard addition yielded �the epimeric mixture 1a in 52% yield followed by a reduction in 98% yield to give the mixture of 2 and 3 in 50% overall yield from 1� (5.3: Chemical Preparations)

                                         Isomers 2 and 3

This chemistry is seen in our experimental in steps 21 to 22 and 22 to 23.

Reagents and conditions: (a) Dess�Martin periodinane, CH₂Cl₂; (b) vinylMgBr, THF, 33% (2 steps); (c) ethynylMgBr, THF, 52% (2 steps). The same reagents and conditions were used in our synthesis.

Articles that cite the above article:

1.  

    McReynolds, M. D.; Dougherty, J. M.; Hanson, P. R. Chem. Rev. 2004, 104, 2239-2258.
 

        Synthesis of phosphorus and sulfur heterocycles via ring-closing olefin metathesis 
 

Cited information about past experimentation important to this synthesis:

In 2000, Nielsen and co-workers described the first examples of ring-closing olefin metathesis (RCM) to cyclic phosphates in their efforts to generate conformationally restricted dinucleotides.

2.        

    Freitag, M.; Thomasen, H.; Christensen, N. K.; et al. Tetrahedron 2004, 60, 3775-3786.
 

Ring-closing metathesis based synthesis of bicyclic nucleosides locked in

S-type conformations by hydroxyl functionalised 3 ',4'-trans linkages 

Introduction:
The biological importance of the conformational equilibrium of nucleosides between N-type and S-type conformations following the pseudorotational cycle[1. and 2.] has motivated the preparation of a significant number of synthetic nucleoside analogues mimicking these conformational ranges. Thus, nucleosides with conformationally restricted bi- or tricyclic carbohydrate parts have been intensively studied as building blocks in nucleic acid analogues, (dinucleotides with conformationally restricted cyclic phosphotriester linkages) and/or for potential antiviral agents.

3.        

    Borsting, P.; Freitag, M.; Nielsen, P. Tetrahedron 2004, 60, 10955-10966.
 

Dinucleotides containing two allyl groups by combinations of allyl phosphotriesters, 5-allyl-, 2 '-O-allyl-

and 2 '-arabino-O-allyl uridine derivatives as substrates for ring-closing metathesis 

Introduction:

Neilson was a co-author of this paper, and cited his own paper as a reference and as background material for this paper. He describes how they have focused on the application of RCM in nucleic acid chemistry, and as a result, conformationally restricted bi- and tricyclic nucleoside monomers as well as di- and trinucleotides with large cyclic structures have been achieved.

Other References:

Dess, D. B.; Martin, J. C. J. Org. Chem. 1983, 48, 4155-4156.

Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277-7387.

�Dess-Martin Periodinane� (http://en.wikipedia.org/wiki/Dess-Martin_oxidation)

Accessed 3/19/06.

�Dess-Martin Oxidation�

(http://www.organic-chemistry.org/namedreactions/dess-martin-oxidation.shtm )

            Accessed 3/19/06.