WO2002085848A3 - Synthesis of pancratistatin prodrugs - Google Patents
Synthesis of pancratistatin prodrugs Download PDFInfo
- Publication number
- WO2002085848A3 WO2002085848A3 PCT/US2002/011964 US0211964W WO02085848A3 WO 2002085848 A3 WO2002085848 A3 WO 2002085848A3 US 0211964 W US0211964 W US 0211964W WO 02085848 A3 WO02085848 A3 WO 02085848A3
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- pancratistatin
- phosphate
- prodrugs
- prodrug
- sodium methoxide
- Prior art date
Links
- VREZDOWOLGNDPW-ALTGWBOUSA-N Pancratistatin Chemical compound C1=C2[C@H]3[C@@H](O)[C@H](O)[C@@H](O)[C@@H](O)[C@@H]3NC(=O)C2=C(O)C2=C1OCO2 VREZDOWOLGNDPW-ALTGWBOUSA-N 0.000 title abstract 5
- VREZDOWOLGNDPW-MYVCAWNPSA-N Pancratistatin Natural products O=C1N[C@H]2[C@H](O)[C@H](O)[C@H](O)[C@H](O)[C@@H]2c2c1c(O)c1OCOc1c2 VREZDOWOLGNDPW-MYVCAWNPSA-N 0.000 title abstract 4
- VREZDOWOLGNDPW-UHFFFAOYSA-N pancratistatine Natural products C1=C2C3C(O)C(O)C(O)C(O)C3NC(=O)C2=C(O)C2=C1OCO2 VREZDOWOLGNDPW-UHFFFAOYSA-N 0.000 title abstract 4
- 229940002612 prodrug Drugs 0.000 title abstract 4
- 239000000651 prodrug Substances 0.000 title abstract 4
- 230000015572 biosynthetic process Effects 0.000 title abstract 2
- 238000003786 synthesis reaction Methods 0.000 title abstract 2
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 abstract 4
- 229910019142 PO4 Inorganic materials 0.000 abstract 3
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 abstract 3
- 239000010452 phosphate Substances 0.000 abstract 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 abstract 1
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 abstract 1
- QXNVGIXVLWOKEQ-UHFFFAOYSA-N Disodium Chemical compound [Na][Na] QXNVGIXVLWOKEQ-UHFFFAOYSA-N 0.000 abstract 1
- MJOQJPYNENPSSS-XQHKEYJVSA-N [(3r,4s,5r,6s)-4,5,6-triacetyloxyoxan-3-yl] acetate Chemical compound CC(=O)O[C@@H]1CO[C@@H](OC(C)=O)[C@H](OC(C)=O)[C@H]1OC(C)=O MJOQJPYNENPSSS-XQHKEYJVSA-N 0.000 abstract 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 abstract 1
- 238000006243 chemical reaction Methods 0.000 abstract 1
- ZVJYSSDFOMJWSE-UHFFFAOYSA-N chloro-bis(phenylmethoxy)phosphane Chemical compound C=1C=CC=CC=1COP(Cl)OCC1=CC=CC=C1 ZVJYSSDFOMJWSE-UHFFFAOYSA-N 0.000 abstract 1
- 238000003776 cleavage reaction Methods 0.000 abstract 1
- 238000007327 hydrogenolysis reaction Methods 0.000 abstract 1
- 238000011065 in-situ storage Methods 0.000 abstract 1
- 229910052751 metal Inorganic materials 0.000 abstract 1
- 239000002184 metal Substances 0.000 abstract 1
- RQKYHDHLEMEVDR-UHFFFAOYSA-N oxo-bis(phenylmethoxy)phosphanium Chemical compound C=1C=CC=CC=1CO[P+](=O)OCC1=CC=CC=C1 RQKYHDHLEMEVDR-UHFFFAOYSA-N 0.000 abstract 1
- 230000026731 phosphorylation Effects 0.000 abstract 1
- 238000006366 phosphorylation reaction Methods 0.000 abstract 1
- 125000006239 protecting group Chemical group 0.000 abstract 1
- 238000000746 purification Methods 0.000 abstract 1
- 230000007017 scission Effects 0.000 abstract 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/12—Antivirals
- A61P31/14—Antivirals for RNA viruses
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Virology (AREA)
- Communicable Diseases (AREA)
- Oncology (AREA)
- Biochemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
A new and efficient synthesis of the (+)-pancratistatin phosphate prodrug 2a has been accomplished. Selective protection (tetraacetate 4) of (+)-pancratistatin (1a) was followed by phosphorylation (to 5) with dibenzyl chlorophosphite (prepared in situ from dibenzyl phosphite). Cleavage of the acetate (with sodium methoxide) and benzyl (by hydrogenolysis) protecting groups followed by concomitant reaction with two equivalents of sodium methoxide afforded good yield of disodium (+)-pancratistatin phosphate (2a). Further increases in yields of the prodrug (2a) were realized by avoiding heat in the final purification steps. Fourteen (2b-o) additional metal and ammonium derived phosphate prodrugs were also synthesized.
Priority Applications (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2002583375A JP2005515958A (en) | 2002-04-17 | 2002-04-17 | Synthesis of panclastatin prodrug |
| EP02733993A EP1385846A4 (en) | 2001-04-18 | 2002-04-17 | Synthesis of pancratistatin prodrugs |
| CA002444471A CA2444471A1 (en) | 2001-04-18 | 2002-04-17 | Synthesis of pancratistatin prodrugs |
| US10/475,061 US20040127467A1 (en) | 2002-04-17 | 2002-04-17 | Synthesis of pancratistatin prodrugs |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28471701P | 2001-04-18 | 2001-04-18 | |
| US60/284,717 | 2001-04-18 |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| WO2002085848A2 WO2002085848A2 (en) | 2002-10-31 |
| WO2002085848A3 true WO2002085848A3 (en) | 2003-04-24 |
| WO2002085848A8 WO2002085848A8 (en) | 2003-05-30 |
Family
ID=23091255
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US2002/011964 WO2002085848A2 (en) | 2001-04-18 | 2002-04-17 | Synthesis of pancratistatin prodrugs |
Country Status (3)
| Country | Link |
|---|---|
| EP (1) | EP1385846A4 (en) |
| CA (1) | CA2444471A1 (en) |
| WO (1) | WO2002085848A2 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2016130969A1 (en) | 2015-02-13 | 2016-08-18 | George Robert Pettit | Silstatin compounds |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5529989A (en) * | 1995-01-09 | 1996-06-25 | Arizona Board Of Regents Acting On Behalf Of Arizona State University | Pancratistatin prodrug |
-
2002
- 2002-04-17 CA CA002444471A patent/CA2444471A1/en not_active Abandoned
- 2002-04-17 EP EP02733993A patent/EP1385846A4/en not_active Withdrawn
- 2002-04-17 WO PCT/US2002/011964 patent/WO2002085848A2/en active Application Filing
Non-Patent Citations (2)
| Title |
|---|
| PETTIT G.R.: "Antineoplastic agents 320: synthesis of a practical pancratistatin prodrug", ANTI-CANCER DRUG RES., vol. 10, no. 3, 1995, pages 243 - 250, XP002958298 * |
| See also references of EP1385846A4 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2002085848A8 (en) | 2003-05-30 |
| EP1385846A2 (en) | 2004-02-04 |
| EP1385846A4 (en) | 2005-11-30 |
| WO2002085848A2 (en) | 2002-10-31 |
| CA2444471A1 (en) | 2002-10-31 |
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