Stereoselective synthesis of P-homochiral oligo(thymidine methanephosphonates)

Abstract

An appWroach to the stereoselective synthesis of P-homochiral oligo(thymidine methanephosphonates) i8 described. Fully protected (Rp)-and (Bp)-diastereomers of MMTrTpmeTAc () were prepared in the stereospec I tic react Ion of

Application of phosphonate and thiophosphate analogues of nucleotides to studies of some enzyme reactions

“…In the general case of an unsymmetrical diester (13), one can replace either of the nonbridging oxygens by a carbon function, thereby creating a pair of stereoisomeric phosphonate diesters. The attractiveness of such species as, for example, nonionic, methylphosphonate diester analogues (14) of oligonucleotides has resulted in the application of great skil, to the control of their stereochemistry [9]. Alternatively, one can substitute either of the bridging oxygens of a phosphate diester by carbon functions to create a pair of isomorphous phosphonate monoesters (15), both of which are isosteric and isocoulombic with the prototype phosphate 13 (Scheme 4).…”

Interactions of oligonucleotide analogs containing methylphosphonate internucleotide linkages and 2′-O-methylribonucleosides

“…As shown in Table 2 (28)(29)(30)(31)34). The Tms of the duplexes formed with the Sp isomer are also lower than duplexes with the Rp isomer in buffer lacking sodium chloride, although the reduction is somewhat less relative to that observed in 0.1 M sodium chloride buffer.…”

Electrostatics and hydration at thehomeodomain-DNA interface: chemical probes of an interfacial water cavity

“…Assignment of absolute stereochemistry was obtained by nuclease digestion to the methylphosphonate-linked dimers and subsequent comparison of HPLC elution times with known standards (Lesnikowski et al, 1988(Lesnikowski et al, , 1990Vyazovkina et al, 1993). Seven sites were investigated: positions 6A, 7A and 9A (strand A) and positions 5B, 6B,7B and 9B (strand B;Figures 2C and 5C).…”

“…The stereochemical con®guration of the isolated diasteromers was assigned by hydrolysis with snake venom phosphodiesterase and bacterial alkaline phosphatase into component monomers and the corresponding methylphosphonate dimer, followed by co-injection of dimer standards of known con®guration. Relative HPLC retention times for R p and S p methylphosphonate nucleoside dimers are as described (Lesnikowski et al, 1988(Lesnikowski et al, , 1990 under the following conditions: buffer a, 0.1M NH 4 OAC (pH 5.8); elution solvent b, acetonitrile;¯ow rate, 1 ml/min, C18 column (5m, ODS Hypersil, 100 Â 4.6 mm); elution gradient, 1% solvent b/min at 25 C. Stereopurity (>98%) was evaluated by reverse-phase HPLC.…”