Affinity guided isolation, structure elucidation and total synthesis of laetirobin a and its analogue synthesis for therapeutic development 8

EDUCATION & PROFESSIONAL QUALIFICATIONS National University of Singapore, Singapore Medicinal Chemistry Programme PhD student under the supervision of Dr.. Martin Lear • Affinity-Guide

X-ray Data

Identification code 8309

Empirical formula C45 H33 Cl3 O12

Unit cell dimensions a = 10.9989(12) Å α= 112.139(2)°

b = 13.8100(14) Å β= 90.723(3)°

c = 14.2340(15) Å γ = 94.576(3)°

Density (calculated) 1.452 Mg/m3

Absorption coefficient 0.297 mm-1

Theta range for data collection 1.55 to 27.49°

Index ranges -14<=h<=10, -15<=k<=17, -18<=l<=17

Independent reflections 9076 [R(int) = 0.0342]

Completeness to theta = 27.49° 99.1 %

Absorption correction Sadabs, (Sheldrick 2001)

Max and min transmission 0.9766 and 0.9540

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 9076 / 0 / 549

Final R indices [I>2sigma(I)] R1 = 0.0709, wR2 = 0.1967

R indices (all data) R1 = 0.1076, wR2 = 0.2243

Largest diff peak and hole 0.606 and -0.620 e.Å-3

Identification code 9103

Empirical formula C44.50 H34 O12.50

Unit cell dimensions a = 11.9232(17) Å α= 97.200(3)°

b = 12.0133(16) Å β= 109.150(3)°

c = 13.613(2) Å γ = 90.874(3)°

Density (calculated) 1.400 Mg/m3

Absorption coefficient 0.103 mm-1

Theta range for data collection 1.60 to 27.50°

Index ranges -15<=h<=15, -15<=k<=12, -13<=l<=17

Independent reflections 8291 [R(int) = 0.0276]

Completeness to theta = 27.50° 98.9 %

Absorption correction Semi-empirical from equivalents

Max and min transmission 0.9817 and 0.9600

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 8291 / 13 / 534

Final R indices [I>2sigma(I)] R1 = 0.0759, wR2 = 0.2006

R indices (all data) R1 = 0.1162, wR2 = 0.2258

Largest diff peak and hole 0.919 and -0.317 e.Å-3

Identification code 7498

Unit cell dimensions a = 12.5415(10) Å α= 90°

b = 6.7365(5) Å β= 102.770(2)°

c = 13.0122(11) Å γ = 90°

Density (calculated) 1.141 Mg/m3

Absorption coefficient 0.071 mm-1

Theta range for data collection 1.66 to 27.48°

Index ranges -16<=h<=16, -5<=k<=8, -16<=l<=16

Independent reflections 2458 [R(int) = 0.0271]

Completeness to theta = 27.48° 99.8 %

Absorption correction Sadabs, (Sheldrick 2001)

Max and min transmission 0.9888 and 0.9456

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 2458 / 0 / 128

Final R indices [I>2sigma(I)] R1 = 0.0468, wR2 = 0.1108

R indices (all data) R1 = 0.0580, wR2 = 0.1169

Largest diff peak and hole 0.215 and -0.172 e.Å-3

Identification code a502

Unit cell dimensions a = 11.1434(9) Å α= 90°

b = 16.8307(13) Å β= 92.116(2)°

c = 16.9033(13) Å γ = 90°

Density (calculated) 1.436 Mg/m3

Absorption coefficient 0.230 mm-1

Theta range for data collection 1.71 to 27.50°

Index ranges -14<=h<=14, -20<=k<=21, -21<=l<=14

Independent reflections 7254 [R(int) = 0.0477]

Completeness to theta = 27.50° 99.8 %

Absorption correction Semi-empirical from equivalents

Max and min transmission 0.9685 and 0.8937

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 7254 / 0 / 437

Final R indices [I>2sigma(I)] R1 = 0.0678, wR2 = 0.1535

R indices (all data) R1 = 0.0894, wR2 = 0.1645

Largest diff peak and hole 0.409 and -0.349 e.Å-3

Identification code 9058a

Unit cell dimensions a = 10.0478(6) Å α= 90°

b = 28.418(2) Å β= 105.343(2)°

c = 9.3323(6) Å γ = 90°

Density (calculated) 1.346 Mg/m3

Absorption coefficient 0.087 mm-1

Theta range for data collection 2.10 to 27.50°

Index ranges -13<=h<=10, -32<=k<=36, -12<=l<=12

Independent reflections 5865 [R(int) = 0.0421]

Completeness to theta = 27.50° 99.5 %

Absorption correction Semi-empirical from equivalents

Max and min transmission 0.9931 and 0.9594

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 5865 / 6 / 401

Final R indices [I>2sigma(I)] R1 = 0.0626, wR2 = 0.1441

R indices (all data) R1 = 0.0885, wR2 = 0.1566

Largest diff peak and hole 0.277 and -0.211 e.Å-3

Identification code 9156

Unit cell dimensions a = 9.6753(4) Å α= 72.7480(10)°

b = 11.4318(5) Å β= 79.5670(10)°

c = 12.7153(5) Å γ = 69.6640(10)°

Density (calculated) 1.378 Mg/m3

Absorption coefficient 0.089 mm-1

Theta range for data collection 1.68 to 27.50°

Index ranges -12<=h<=12, -14<=k<=14, -16<=l<=16

Independent reflections 5751 [R(int) = 0.0241]

Completeness to theta = 27.50° 99.8 %

Absorption correction Semi-empirical from equivalents

Max and min transmission 0.9929 and 0.9720

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 5751 / 0 / 362

Final R indices [I>2sigma(I)] R1 = 0.0454, wR2 = 0.1130

R indices (all data) R1 = 0.0508, wR2 = 0.1171

Largest diff peak and hole 0.280 and -0.247 e.Å-3

Identification code 9569

Empirical formula C51 H43 I O4 P2 Pd S

Unit cell dimensions a = 17.2514(6) Å α= 90°

b = 11.3058(4) Å β= 108.9530(10)°

c = 23.7741(9) Å γ = 90°

Density (calculated) 1.586 Mg/m3

Absorption coefficient 1.294 mm-1

Theta range for data collection 1.28 to 27.47°

Index ranges -16<=h<=22, -14<=k<=14, -30<=l<=29

Independent reflections 10023 [R(int) = 0.0409]

Completeness to theta = 27.47° 99.9 %

Absorption correction Semi-empirical from equivalents

Max and min transmission 0.8815 and 0.7133

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 10023 / 0 / 543

Final R indices [I>2sigma(I)] R1 = 0.0507, wR2 = 0.1127

R indices (all data) R1 = 0.0597, wR2 = 0.1194

Largest diff peak and hole 2.012 and -0.961 e.Å-3

Identification code a181

Unit cell dimensions a = 9.217(2) Å α= 95.368(5)°

b = 9.311(2) Å β= 103.158(4)°

c = 11.753(3) Å γ = 104.872(5)°

Density (calculated) 1.334 Mg/m3

Absorption coefficient 0.090 mm-1

Theta range for data collection 1.80 to 27.48°

Index ranges -11<=h<=11, -12<=k<=12, -15<=l<=15

Independent reflections 4266 [R(int) = 0.0309]

Completeness to theta = 27.48° 99.4 %

Absorption correction Semi-empirical from equivalents

Max and min transmission 0.9875 and 0.9514

Refinement method Full-matrix least-squares on F2

Data / restraints / parameters 4266 / 0 / 253

Final R indices [I>2sigma(I)] R1 = 0.0501, wR2 = 0.1238

R indices (all data) R1 = 0.0572, wR2 = 0.1289

Largest diff peak and hole 0.544 and -0.208 e.Å-3

EDUCATION & PROFESSIONAL QUALIFICATIONS

National University of Singapore, Singapore

Medicinal Chemistry Programme (PhD student under the supervision of Dr Martin Lear)

• Affinity-Guided Isolation, Structure Elucidation and Total Synthesis of Laetirobin A and

Its Analogue Synthesis for Therapeutic Development

Distance Teaching University, Hagen, Germany

2007 - 2011

2005 - 2006

Economic Sciences

Graduate of Pharmaceutical Chemistry (“Diplom-Ing.”)

genic immunoassays done in cooperation with the Roche Diagnostics Department of

Rare Reagents

Today part of the Sanofi-Aventis group

Chemical Technician Apprenticeship and Qualification

• Completed processed-oriented apprenticeship in only 2.5 years instead of 3 due to excellent

work results

PROFESSIONAL EXPERIENCE

Novartis Institute for Tropical Diseases, Singapore

Research Investigator – Chemistry

Development of anti-malaria therapeutics

Boehringer Ingelheim, Vienna, Austria

2011 - present

2001 - 2006

German Armed Forces, Gerolstein, Germany

1995 - 1996

National military service in the Army’s Communication Corps

PUBLICATIONS & PATENTS

2010

Simon, O.; Reux, B.; La Clair, J J.; Lear, M J Total Synthesis Confirms Laetirobin as a Formal Diels–Alder

Adduct Chem-Asian J 2010, 5, 342-351

2009

Lear, M J., Simon, O., Foley, T L., Burkart, M D., Baiga, T J., Noel, J P., DiPasquale, A G., Rheingold, A L.,

La Clair, J J Laetirobin from the parasitic growth of Laetiporus sulphureus on Robinia pseudoacacia J Nat

Prod 2009, 72, 1980-87

2006

Betzemeier, B., Brandl, T., Breitfelder, S., Brueckner, R., Gerstberger, T., Gmachl, M., Grauert, M., Hilberg, F., Hoenke, C., Hoffmann, M., Impagnatiello, M., Kessler, D., Klein, C., Krist, B., Maier, U., McConnell, D., Reither,

C., Scheuerer, S., Schoop, A., Schweifer, N., Simon, O., Steegmaier, M., Steurer, S., Waizenegger, I.,

Weyer-Czernilofsky, U., Zoephel, A Preparation of thiazoloindazoles for treatment and prevention of cancer Patent:

WO 2006040281 (Boehringer Ingelheim International GmbH, Germany; Boehringer Ingelheim Pharma GmbH &

Co KG) 131 pp

2002

Heindl, D., Herrmann R., Josel, H.-P., Huber, E., Klause, U., Simon, O Luciferin hydrazides Patent: WO

2002099428 (Roche Diagnostics GmbH., Germany; F Hoffmann-La Roche AG) 35 pp

CONFERENCE PRESENTATIONS

6th Singapore International Chemistry Conference (SICC 6), Singapore, 2009

Reux B., Simon O., La Clair J J., Lear M J Total Synthesis of Laetirobin: a Late-Stage Mitotic Blocker that

Induces Cell Death (poster presentation)

Simon O., Reux B., La Clair J J., Lear M J Discovery of Laetirobin as a Late-Stage Mitotic Blocker

that Induces Programmed Cell Death (poster presentation)

Lear M J., Simon O., Foley T L., Burkart M D., Baiga T J., Noel J P., DiPasquale A G., Rheingold A L., La

Clair J J Discovery of Laetiporina A as a Selective Mitotic Blocker (poster presentation)

PROFESSIONAL POSITIONS

Member 2009 - present

American Chemical Society

• English: written and spoken

COMPUTER PROFICIENCY

ACTIVITIES & INTERESTS

• Travelling (Africa, Asia, Australia, Europe)

PERSONAL PARTICULARS

• Marital status: Single

Singapore, 03rd May 2011