A highly efficient chemical synthesis of Rp and Sp adenyl(3′-5′)adenyl-o,o-phosphorothioate

John F. Marlier; Stephen J. Benkovic

doi:10.1016/S0040-4039(01)83929-0

A highly efficient chemical synthesis of Rp and Sp adenyl(3′-5′)adenyl-o,o-phosphorothioate

John F. Marlier
, Stephen J. Benkovic

Chemistry

Research output: Contribution to journal › Article › peer-review

37 Scopus citations

Abstract

A method is described for the chemical synthesis of the title compounds (Ap(S)A) via addition of elemental sulfur to a phosphite triester intermediate. Separation of the diastereomers of phosphorus could be accomplished on silica gel after removal of the terminal 5′-hydroxyl protecting group or on DEAE cellulose after complete deblocking. The triester to terminal 5′-hydroxyl. The overall yield of the synthesis (one coupling and four deblocking steps) is 30%.

Original language	English (US)
Pages (from-to)	1121-1124
Number of pages	4
Journal	Tetrahedron Letters
Volume	21
Issue number	12
DOIs	https://doi.org/10.1016/S0040-4039(01)83929-0
State	Published - 1980

All Science Journal Classification (ASJC) codes

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/S0040-4039(01)83929-0

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@article{a341082d4bc1434991537336c3fd2818,

title = "A highly efficient chemical synthesis of Rp and Sp adenyl(3′-5′)adenyl-o,o-phosphorothioate",

abstract = "A method is described for the chemical synthesis of the title compounds (Ap(S)A) via addition of elemental sulfur to a phosphite triester intermediate. Separation of the diastereomers of phosphorus could be accomplished on silica gel after removal of the terminal 5′-hydroxyl protecting group or on DEAE cellulose after complete deblocking. The triester to terminal 5′-hydroxyl. The overall yield of the synthesis (one coupling and four deblocking steps) is 30\%.",

author = "Marlier, \{John F.\} and Benkovic, \{Stephen J.\}",

note = "Funding Information: for the Sp diastereomer. By analogy, one might expect the resonance at 56.8 ppm for Ap( to be due to the diastereomer with the Rp configuration. To firmly establish the absolute stereochemistry for Ap(S the hydrolysis of a 50:50 mixture of the diastereomers by bovine intestinal phosphodiesterase 13 was followed by P 31 nmr. After 3 hours the resonance at 56.8 ppm had decreased by approximately one half and that at 55.7 ppm showed no change. Since it is known that the bovine diesterase is stereoselective for dinucleotides with the Rp configuration at phosphorus2, the resonance at 56.8 ppm is that from the compoundw ith the Rp configuration, 5\_a, consistent with the above tentative assignment based on the P31 data for Up(S)A.14 Acknowledgement This research was supported by grant GM 13306 from the National Institutes of Health. We are grateful to Mr. Randy Bryant for running the final DEAE columns and to Dr. Larry Butler for a gift of bovine phosphodiesterase.",

year = "1980",

doi = "10.1016/S0040-4039(01)83929-0",

language = "English (US)",

volume = "21",

pages = "1121--1124",

journal = "Tetrahedron Letters",

issn = "0040-4039",

publisher = "Elsevier Ltd",

number = "12",

}

TY - JOUR

T1 - A highly efficient chemical synthesis of Rp and Sp adenyl(3′-5′)adenyl-o,o-phosphorothioate

AU - Marlier, John F.

AU - Benkovic, Stephen J.

N1 - Funding Information: for the Sp diastereomer. By analogy, one might expect the resonance at 56.8 ppm for Ap( to be due to the diastereomer with the Rp configuration. To firmly establish the absolute stereochemistry for Ap(S the hydrolysis of a 50:50 mixture of the diastereomers by bovine intestinal phosphodiesterase 13 was followed by P 31 nmr. After 3 hours the resonance at 56.8 ppm had decreased by approximately one half and that at 55.7 ppm showed no change. Since it is known that the bovine diesterase is stereoselective for dinucleotides with the Rp configuration at phosphorus2, the resonance at 56.8 ppm is that from the compoundw ith the Rp configuration, 5_a, consistent with the above tentative assignment based on the P31 data for Up(S)A.14 Acknowledgement This research was supported by grant GM 13306 from the National Institutes of Health. We are grateful to Mr. Randy Bryant for running the final DEAE columns and to Dr. Larry Butler for a gift of bovine phosphodiesterase.

PY - 1980

Y1 - 1980

N2 - A method is described for the chemical synthesis of the title compounds (Ap(S)A) via addition of elemental sulfur to a phosphite triester intermediate. Separation of the diastereomers of phosphorus could be accomplished on silica gel after removal of the terminal 5′-hydroxyl protecting group or on DEAE cellulose after complete deblocking. The triester to terminal 5′-hydroxyl. The overall yield of the synthesis (one coupling and four deblocking steps) is 30%.

AB - A method is described for the chemical synthesis of the title compounds (Ap(S)A) via addition of elemental sulfur to a phosphite triester intermediate. Separation of the diastereomers of phosphorus could be accomplished on silica gel after removal of the terminal 5′-hydroxyl protecting group or on DEAE cellulose after complete deblocking. The triester to terminal 5′-hydroxyl. The overall yield of the synthesis (one coupling and four deblocking steps) is 30%.

UR - https://www.scopus.com/pages/publications/0039314345

UR - https://www.scopus.com/pages/publications/0039314345#tab=citedBy

U2 - 10.1016/S0040-4039(01)83929-0

DO - 10.1016/S0040-4039(01)83929-0

M3 - Article

AN - SCOPUS:0039314345

SN - 0040-4039

VL - 21

SP - 1121

EP - 1124

JO - Tetrahedron Letters

JF - Tetrahedron Letters

IS - 12

ER -

A highly efficient chemical synthesis of Rp and Sp adenyl(3′-5′)adenyl-o,o-phosphorothioate

Abstract

All Science Journal Classification (ASJC) codes

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