Synthesis of Prostaglandin Analogues, Latanoprost and Bimatoprost, Using Organocatalysis via a Key Bicyclic Enal Intermediate

Synthesis of Prostaglandin Analogues, Latanoprost and Bimatoprost, Using Organocatalysis via a Key Bicyclic Enal Intermediate

Sébastien Prévost , Karen Thai , Nina Schützenmeister , Graeme Coulthard , William Erb , and Varinder K. Aggarwal *

School of Chemistry, University of Bristol, Cantock’s Close, Bristol, BS8 1TS, U.K.

Org. Lett., Article ASAP

DOI: 10.1021/ol503520f

Publication Date (Web): January 12, 2015

Copyright © 2015 American Chemical Society

*E-mail: v.aggarwal@bristol.ac.uk.

Two antiglaucoma drugs, bimatoprost and latanoprost, which are analogues of the prostaglandin, PGF2α, have been synthesized in just 7 and 8 steps, respectively. The syntheses employ an organocatalytic aldol reaction that converts succinaldehyde into a key bicyclic enal intermediate, which is primed for attachment of the required lower and upper side chains. By utilizing the crystalline lactone, the drug molecules were prepared in >99% ee.

Professor Varinder Aggarwal 
BA, PhD(Cantab), FRS

Professor

Area of research

Asymmetric synthesis, methodology and applications.

Office N226
Cantock's Close,Clifton, Bristol BS8 1TS(See a map)

Tel. +44 (0) 117 954 6315
v.aggarwal@bristol.ac.uk

http://www.chm.bris.ac.uk/org/aggarwal/

School of Chemistry

HIGHLIGHTS

2014
• Nature: Assembly-line synthesis
• Nature Chemistry: Traceless coupling
• Nature Chemistry: sp2-sp3 Coupling
2012
• RSC Symposium: Sven Fritz wins Best Oral presentation
• Nature: Synthesis of prostaglandin PGF2a
• FRS: Varinder elected a Fellow of the Royal Society!
• University College of Dublin: Cath Fletcher wins Best Poster Prize. 
2010
• RSC Symposium: Muhammad Arshad wins Best Prize Prize
• Varinder appears on TV!
2009
• Mike Shaw is awarded Fulbright Distinguished Scholar Fellowship.
2008
• Nature: Enantioselective Conversion of Secondary Alcohols into Tertiary Alcohols

Asymmetric synthesis, methodology and applications.

My research interests include; the development of new catalytic processes for asymmetric synthesis; the development of chiral carbenoids and their use and subsequent applications in catalysis and synthesis; the development of new methodology and its applications in synthesis; total synthesis of biologically important targets.

Research keywords

• catalytic processes
• asymmetric synthesis
• reactive intermediates
• synthesis
• carbenes
• carbenoids

Latest publications

• Bonet, A, Odachowski, M, Leonori, D, Essafi, S & Aggarwal, VK 2014, ‘Enantiospecific sp(2)-sp(3) coupling of secondary and tertiary boronic esters’. NATURE CHEMISTRY, vol 6., pp. 584-589
• Hesse, MJ, Essafi, S, Watson, CG, Harvey, JN, Hirst, D, Willis, CL & Aggarwal, VK 2014, ‘Highly Selective Allylborations of Aldehydes Using alpha,alpha-Disubstituted Allylic Pinacol Boronic Esters’. Angewandte Chemie International Edition, vol 53., pp. 6145-6149
• Blair, DJ, Fletcher, CJ, Wheelhouse, KMP & Aggarwal, VK 2014, ‘Stereocontrolled Synthesis of Adjacent Acyclic Quaternary-Tertiary Motifs: Application to a Concise Total Synthesis of (-)-Filiformin’. Angewandte Chemie International Edition, vol 53., pp. 5552-5555
• Pulis, AP, Fackler, P & Aggarwal, VK 2014, ‘Short Stereoselective Synthesis of the Phytophthora Universal Mating Hormone alpha 1 Using Lithiation/Borylation Reactions’. Angewandte Chemie International Edition, vol 53., pp. 4382-4385
• Mohiti, M, Rampalakos, K, Feeney, KMJ, Leonori, D & Aggarwal, VK 2014, ‘Asymmetric addition of chiral boron-ate complexes to cyclic iminium ions’. Chemical Science, vol 5., pp. 602-607
• Roesner, S, Brown, CA, Mohiti, M, Pulis, AP, Rasappan, R, Blair, DJ, Essafi, S, Leonori, D & Aggarwal, VK 2014,‘Stereospecific conversion of alcohols into pinacol boronic esters using lithiation-borylation methodology with pinacolborane’. Chemical Engineering Communications, vol 50., pp. 4053-4055

Cantock's Close

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