departmentof chemistry, chemistry research laboratory, university of oxford… · 2017-06-14 ·...
TRANSCRIPT
![Page 1: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/1.jpg)
• SUPPORTING INFORMATION••• Synthesisandbioactivityoffused- andspiro-b-lactone-lactamsystems•• Laia Josa-Culleré,a ChristopherTowers,b FrancesWillenbrock,b ValentineM.Macaulay,b KirstenE.
Christensena andMarkG.Moloney*b•• DepartmentofChemistry,ChemistryResearchLaboratory,TheUniversityofOxford,12Mansfield
Road,Oxford.OX13TA.
• aDepartment ofChemistry,ChemistryResearchLaboratory,UniversityofOxford,12MansfieldRoad,Oxford,OX13TA,UK.E-mail:[email protected].
• bDepartment ofOncology,UniversityofOxford,OldRoadCampusResearchBuilding,Oxford,OX37LJ,UK.
• e-mail:[email protected]•••
Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry.This journal is © The Royal Society of Chemistry 2017
![Page 2: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/2.jpg)
NH HO
OCO2Me
O
10
H2O
MeOH
![Page 3: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/3.jpg)
NH HO
OCO2Me
O
10
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NO
CO2MeO
OMe
15
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NO
CO2MeO
OMe
15
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NO
CO2MeO
OBn
16
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NO
CO2MeO
OBn
16
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NH HO
OCO2Me
OH
17
**
*impurity
H2O
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NH HO
OCO2Me
OH
17
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NH HO
OCO2Me
OMe
18
H2O
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NH HO
OCO2Me
OMe
18
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NH HO
OCO2Me
OBn
19
H2O
MeOH
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NH HO
OCO2Me
OBn
19
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NH HO
OCO2H
OMe
21
H2O
MeOH
*
*impurity
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NH HO
OCO2H
OMe
21
![Page 16: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/16.jpg)
NH HO
OCO2H
OBn
22
H2ODCM
*
*impurity
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NH HO
OCO2H
OBn
22
![Page 18: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/18.jpg)
NH HO
O
O O
23
H2O
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NH HO
O
O O
23
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NH O
O
O O
O
24
H2O
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NH O
O
O O
O
24
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NH O
O
O O
O
24
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NH
O
OMe
O
O
26
H2O
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NH
O
OMe
O
O
26
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N O
MeO2C
O O
28
H2O
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N O
MeO2C
O O
28
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N O
MeO2C
O OBnO
29
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N O
MeO2C
O OBnO
29
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NO
CO2MeO
Me OHMe
30a
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NO
CO2MeO
Me OHMe
30a
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NO
CO2MeO
Me OHMe
30b
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NO
CO2MeO
Me OHMe
30b
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NO
CO2MeO
Me OHOBn
31a
H2O
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NO
CO2MeO
Me OHOBn
31a
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NO
OCO2Me
HH
OH
H
MeH
OBn
31a
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NO
CO2MeO
Me OHOBn
31b
H2O
![Page 37: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/37.jpg)
NO
CO2MeO
Me OHOBn
31b
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NH HO
CO2MeO
Me OHMe
32a
H2O
DCM
![Page 39: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/39.jpg)
NH HO
CO2MeO
Me OHMe
32a
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NH HO
CO2MeO
Me OHMe
32b
H2O
![Page 41: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/41.jpg)
NH HO
CO2MeO
Me OHMe
32b
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NH HO
CO2MeO
Me OHOBn
33a
H2O
![Page 43: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/43.jpg)
NH HO
CO2MeO
Me OHOBn
33a
![Page 44: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/44.jpg)
NH HO
CO2MeO
Me OHOBn
33b
H2O
![Page 45: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/45.jpg)
NH HO
CO2MeO
Me OHOBn
33b
![Page 46: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/46.jpg)
NH HO
O
Me MeO
O
34 H2O
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NH HO
O
Me MeO
O
34
![Page 48: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/48.jpg)
H2O
NH HO
CO2HO
Me OHOBn
47b
![Page 49: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/49.jpg)
NH HO
CO2HO
Me OHOBn
47b
![Page 50: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/50.jpg)
NH HO
O
Me O
O
OBn
35H2O
* *
*impurity
![Page 51: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/51.jpg)
NH HO
O
Me O
O
OBn
35
![Page 52: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/52.jpg)
NH
O O
OMe OHMe
36
H2O
![Page 53: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/53.jpg)
NH
O O
OMe OHMe
36
![Page 54: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/54.jpg)
H2O
DCM*
*impurity
NH HO
CO2HO
Me OHOBn
47a
![Page 55: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/55.jpg)
NH HO
CO2HO
Me OHOBn
47a
![Page 56: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/56.jpg)
NH
O O
OMe OH
37
OBn
H2O
![Page 57: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/57.jpg)
NH
O O
OMe OH
37
OBn
![Page 58: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/58.jpg)
N O
MeO2C
OOBnO
Me
38
![Page 59: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/59.jpg)
N O
MeO2C
OOBnO
Me
38
![Page 60: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/60.jpg)
NO
CO2MeO
Me OHOBn
Me
39
![Page 61: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/61.jpg)
NO
CO2MeO
Me OHOBn
Me
39
![Page 62: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/62.jpg)
NO
OCO2Me
MeH
OH
H
MeH
OBn
39
![Page 63: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/63.jpg)
NH HO
CO2MeO
Me OHOBn
Me
40a
H2O
EtOAcEtOAc
![Page 64: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/64.jpg)
NH HO
CO2MeO
Me OHOBn
Me
40a
![Page 65: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam](https://reader036.vdocument.in/reader036/viewer/2022080722/5f7b81481ca1e345142730e8/html5/thumbnails/65.jpg)
NH HO
O
Me O
O
OBn
MeNH
O O
OMe OH
42
OBn
Me43
or
H2O
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NH HO
O
Me O
O
OBn
MeNH
O O
OMe OH
42
OBn
Me43
or
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NO
CO2MeO
Me OHOH
45
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NO
CO2MeO
Me OHOH
45
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NO
O
Me HOO
O
46
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NO
O
Me HOO
O
46