Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation
By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor f...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Chemical Society (ACS)
2022
|
| Online Access: | https://hdl.handle.net/1721.1/141085 |
| _version_ | 1826209977049546752 |
|---|---|
| author | Mear, Sarah Jane Nguyen, Long V Rochford, Ashley J Jamison, Timothy F |
| author_facet | Mear, Sarah Jane Nguyen, Long V Rochford, Ashley J Jamison, Timothy F |
| author_sort | Mear, Sarah Jane |
| collection | MIT |
| description | By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to 95% yield and >20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from a tartrate diester. |
| first_indexed | 2024-09-23T14:38:08Z |
| format | Article |
| id | mit-1721.1/141085 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:38:08Z |
| publishDate | 2022 |
| publisher | American Chemical Society (ACS) |
| record_format | dspace |
| spelling | mit-1721.1/1410852022-03-10T03:10:51Z Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation Mear, Sarah Jane Nguyen, Long V Rochford, Ashley J Jamison, Timothy F By simple combination of water and sodium iodide (NaI) with chlorotrimethylsilane (TMSCl), promotion of a Vorbrüggen glycosylation en route to essential HIV drugs emtricitabine (FTC) and lamivudine (3TC) is achieved. TMSCl-NaI in wet solvent (0.1 M water) activates a 1,3-oxathiolanyl acetate donor for N-glycosylation of silylated cytosine derivatives, leading to cis-oxathiolane products with up to 95% yield and >20:1 dr. This telescoped sequence is followed by recrystallization and borohydride reduction, resulting in rapid synthesis of (±)-FTC/3TC from a tartrate diester. 2022-03-09T15:48:51Z 2022-03-09T15:48:51Z 2022-01-14 2022-03-09T15:40:53Z Article http://purl.org/eprint/type/JournalArticle https://hdl.handle.net/1721.1/141085 Mear, Sarah Jane, Nguyen, Long V, Rochford, Ashley J and Jamison, Timothy F. 2022. "Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation." The Journal of Organic Chemistry. en 10.1021/acs.joc.1c02772 The Journal of Organic Chemistry Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Chemical Society (ACS) chemRxiv |
| spellingShingle | Mear, Sarah Jane Nguyen, Long V Rochford, Ashley J Jamison, Timothy F Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation |
| title | Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation |
| title_full | Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation |
| title_fullStr | Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation |
| title_full_unstemmed | Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation |
| title_short | Synthesis of (±)-Emtricitabine and (±)-Lamivudine by Chlorotrimethylsilane–Sodium Iodide-Promoted Vorbrüggen Glycosylation |
| title_sort | synthesis of emtricitabine and lamivudine by chlorotrimethylsilane sodium iodide promoted vorbruggen glycosylation |
| url | https://hdl.handle.net/1721.1/141085 |
| work_keys_str_mv | AT mearsarahjane synthesisofemtricitabineandlamivudinebychlorotrimethylsilanesodiumiodidepromotedvorbruggenglycosylation AT nguyenlongv synthesisofemtricitabineandlamivudinebychlorotrimethylsilanesodiumiodidepromotedvorbruggenglycosylation AT rochfordashleyj synthesisofemtricitabineandlamivudinebychlorotrimethylsilanesodiumiodidepromotedvorbruggenglycosylation AT jamisontimothyf synthesisofemtricitabineandlamivudinebychlorotrimethylsilanesodiumiodidepromotedvorbruggenglycosylation |