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SUPPORTING INFORMATION Synthesis and bioactivity of fused- and spiro-b-lactone-lactam systems Laia Josa-Culleré, a Christopher Towers, b Frances Willenbrock, b Valentine M. Macaulay, b Kirsten E. Christensen a and Mark G. Moloney* b Department of Chemistry, Chemistry Research Laboratory, The University of Oxford, 12 Mansfield Road, Oxford. OX1 3TA. a Department of Chemistry, Chemistry Research Laboratory, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK. E-mail: [email protected]. b Department of Oncology, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7LJ, UK. e-mail: [email protected] Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry. This journal is © The Royal Society of Chemistry 2017
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Page 1: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

• 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

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

NH HO

OCO2Me

O

10

Page 4: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

OMe

15

Page 5: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

OMe

15

Page 6: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

OBn

16

Page 7: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

OBn

16

Page 8: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

OCO2Me

OH

17

**

*impurity

H2O

Page 9: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

OCO2Me

OH

17

Page 10: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

OCO2Me

OMe

18

H2O

Page 11: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

OCO2Me

OMe

18

Page 12: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

OCO2Me

OBn

19

H2O

MeOH

Page 13: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

OCO2Me

OBn

19

Page 14: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

OCO2H

OMe

21

H2O

MeOH

*

*impurity

Page 15: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

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

NH HO

OCO2H

OBn

22

H2ODCM

*

*impurity

Page 17: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

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

NH HO

O

O O

23

H2O

Page 19: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

O

O O

23

Page 20: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH O

O

O O

O

24

H2O

Page 21: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH O

O

O O

O

24

Page 22: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH O

O

O O

O

24

Page 23: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH

O

OMe

O

O

26

H2O

Page 24: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH

O

OMe

O

O

26

Page 25: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

N O

MeO2C

O O

28

H2O

Page 26: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

N O

MeO2C

O O

28

Page 27: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

N O

MeO2C

O OBnO

29

Page 28: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

N O

MeO2C

O OBnO

29

Page 29: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHMe

30a

Page 30: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHMe

30a

Page 31: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHMe

30b

Page 32: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHMe

30b

Page 33: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHOBn

31a

H2O

Page 34: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHOBn

31a

Page 35: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

OCO2Me

HH

OH

H

MeH

OBn

31a

Page 36: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

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

NO

CO2MeO

Me OHOBn

31b

Page 38: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

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

NH HO

CO2MeO

Me OHMe

32a

Page 40: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

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

NH HO

CO2MeO

Me OHMe

32b

Page 42: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

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

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

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

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

NH HO

O

Me MeO

O

34 H2O

Page 47: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

NH HO

O

Me O

O

OBn

MeNH

O O

OMe OH

42

OBn

Me43

or

H2O

Page 66: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NH HO

O

Me O

O

OBn

MeNH

O O

OMe OH

42

OBn

Me43

or

Page 67: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHOH

45

Page 68: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

CO2MeO

Me OHOH

45

Page 69: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

O

Me HOO

O

46

Page 70: Departmentof Chemistry, Chemistry Research Laboratory, University of Oxford… · 2017-06-14 · •SUPPORTINGINFORMATION • • • Synthesis and bioactivity of fused-and spiro-b-lactone-lactam

NO

O

Me HOO

O

46


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