Nonionic nucleic acid alkyl and aryl phosphonates and processes

Details Nonionic nucleic acid alkyl and aryl phosphonates and processes Nonionic nucleic acid alkyl and aryl phosphonates and processes

1980-11-12

1984-09-04

Hazel, Blondel

Organic compounds -- part of the class 532-570 series

Organic compounds

Carbohydrates or derivatives

536 28, 536 29, C07H 2102, C07H 2104, C07H 2100

Patent

active

044698631

ABSTRACT:
Oligonucleoside alkyl-- or aryl phosphonates are nonionic analogues of nucleic acid which possess unique physical and biological properties. These properties enable the analogues to enter living cells intact and to bind with specifically selected nucleic acids within the cell. As a result, the analogues can specifically inhibit the function or expression of a preselected nucleic acid sequence. Thus the analogues could be used to specifically inhibit the growth of tumor cells or replication of viruses in infected cells.
Four methods are provided for preparing oligonucleoside methylphosphonates: (1) Coupling a protected nucleoside 3'-alkyl or aryl phosphonate with the 5'-hydroxyl group of a protected nucleoside using a condensing agent; (2) Coupling protected nucleoside 3'-alkyl or aryl phosphonic acid derivative with the 5'-hydroxy group of a protected nucleoside with the activated alkyl or aryl phosphonic acid derivative possessing functionalities which are good leaving groups; (3) Coupling a protected nucleoside 3'-alkyl or aryl phosphinate derivative with the 5'-hydroxyl group of a protected nucleoside with the resulting phosphinate derivative being then oxidized to the phosphonate; and (4) Converting a oligonucleoside methoxyphosphite derivative to the alkyl or aryl phosphonate derivative by reaction with an alkyl or aryl iodide. It has been demonstrated that procedures (1) and (2) can be used to prepare oligonucleoside methylphosphonates. Others have shown that procedure (4) can be used to prepare a diribonucleoside methylphosphonate.

REFERENCES:
patent: 3560478 (1971-02-01), Myer
Agarwal, K., and Reftina, F., Nucleic Acids Research, vol. 6, pp. 3009-3024, 1979.
Miller, P., et al., Biochemistry, vol. 18, pp. 5134-5143, 1979, vol. 20, pp. 1874-1880, 1981.
Nemer, M. and Ogilvie, K., Tetrahedron Letters, vol. 21, pp. 4149-4152, 1980.
Miller, P., et al., Federation Proceedings, Abstract 2231, vol. 36, 1977.
Miller, P., et al., J. Am. Chem. Soc., vol. 93, pp. 6657-6665, 1971.
Pless, R., et al., Biochem., vol. 16, pp. 1239-1250, 1977.
Jayarama, K., et al., Proc. Natl. Acad. Sci., vol. 78, pp. 1537-1541, 1977.

Affiliated with

Also associated with

Rating

Nonionic nucleic acid alkyl and aryl phosphonates and processes does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Nonionic nucleic acid alkyl and aryl phosphonates and processes , we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Nonionic nucleic acid alkyl and aryl phosphonates and processes will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-1893099