Abstract

Convergent syntheses of branched tetraribonucleotide 39, nonaribonucleotide 40 and decaribonucleotide 41, modelling the lariat of pre-mRNA processing reaction, are reported. The first key step in the present strategy involves the condensation of the phosphodiester blocks 1, 5 or 15 with the 3',5'-dihydroxy-6-N-benzoyl-2'-O-pixyl(9-phenylxanthen-9-yl)adenosine 29 to give 30a (65%), 31a (63%) or 32a (70%). Chemospecific phosphorylation at 3'-OH of these intermediates afforded the intermediates 30b (92%), 31b (83%) or 32b (80%) which were treated with mild acid to achieve a regiospecific removal of the 2'-O-pixyl group to give compounds 30c (74%), 31c (86%) or 32c (85%). The second key step involved the introduction of biscyanoethylphosphotriester moiety to the 2'-OH of the branch-point adenosine in 30c, 31c or 32c in one single step using (biscyanoethoxy)-(diisopropylamino)phosphine to give the crucial branch-point building blocks 30d (46%), 31d (64%) or 32d (62%) with two dissimilar vicinal phosphates at 2'- and 3'- of the branch-point. These blocks were then converted to the fully protected intermediates 33a (59%) [30d+28 --> 33a], 34a (69%) [31d+19 --> 34a] and 35a (56%) [32d+19 --> 35a], and were subsequently treated with a bulky tertiary amine to give the branch-point 2'-cyanoethylphosphodiester blocks 33b (64%), 34b (67%) and 35b (68%). These were then condensed in the usual way with the appropriate 5'-hydroxy block (27 or 25) to give the fully protected branched oligomers 36 (69%) [33b+27 --> 36], 37 (67%) [34b+25 --> 37] and 38 (63%) [35b+25 --> 38]. These oligomers were then deprotected in the usual manner to give the final branched oligoribonucleotides 39, 40 and 41 in 62%, 21% and 21% yields respectively. Detailed 500 MHz H-1-NMR and 202.4 MHz P-31-NMR studies on 39, 40 and 41 have unequivocally established their purities. Detailed spectroscopic studies such as COSY, HOHAHA & NOESY have also clearly established the structural integrity of the synthetic target compounds.

Published in

Tetrahedron
1991, Volume: 47, number: 32, pages: 6305-6336
Publisher: PERGAMON-ELSEVIER SCIENCE LTD

UKÄ Subject classification

Organic Chemistry


Publication identifier

DOI: https://doi.org/10.1016/S0040-4020(01)86562-5

Permanent link to this page (URI)

https://res.slu.se/id/publ/83882