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Research Interests

Three main research thrusts are in focus:
....(1) Total synthesis, (2) Methodology, (3) Bioimaging.

Within these thrusts, three main biological areas are targeted:
....(1) Malaria, (2) Antibiotics, (3) Biomedical.

To supply natural products for drug discovery, a 3-way international field-trip was undertaken (July 2006) with Xenobe Research Institute (XRI) and Puerto Rico University (UPR).

NUS-based collaborations span across bio-engineering, microbiology, biochemistry, and pharmacy departments within the faculties of engineering, medicine and science.

Non-NUS collaborators stem from the local industry (Merlion), hospital (NUH), univeristy (NTU) and A*STAR institutes (IBN, IMRE), and also from the US (XRI, UPR).


Total Synthesis Programmes
With a view to developing novel antimalarial agents and antibiotics, and to investigate the differing modes of biological activity, synthetic studies toward the total synthesis of Bielschowskysin and Platensimycin are being investigated.

Methodological Programmes
During the advanced stages of making a natural product, we often search for methods to be powerful, yet mild enough to effect a desired transformation. Our group is advancing known, problematic transformations that would otherwise be unsuitable in complex chemical environments. In other words, more chemoselective methods for standard chemical reactions are being developed in the Lear-group. New protective group reagents are highlighted below.

Bioimaging Programmes
In efforts to gain ready access to relevant molecular imaging agents and to speed-up the traditional approaches to drug discovery and development, my group is (1) targeting high-speed synthetic procedures to enable the incorporation of 18F labels, and (2) the production of radiopharmaceuticals and peptide-conjugate probes to study, treat, and detect various disease states for positronic-emission tomography/computed tomography (PET/CT).

Group News and Members
As of Mon. 6th of November, the Lear-group entered their new laboratories (ca. 100 m2, 1100 sq ft) and consists of 6 PhD students and 3 post-doctoral workers.

Representative Publications

Practical synthesis of maleimides and coumarin-linked probes for protein and antibody labelling via reduction of native disulfides, HY Song, MH Ngai, ZY Song, PA MacAry, J Hobley, MJ Lear*, Org. Biomol. Chem. 2009, 7, 3400-3406. (Featured article with inside cover-page).

Total synthesis of a fully lipidated form of phosphatidyl-myo-inositol dimannoside (PIM-2) of Mycobacterium tuberculosis, A Ali, MR Wenk, MJ Lear*, Tetrahedron Lett. 2009, 50, 5664-5666.

A mild method for the protection of alcohols using a para-methoxybenzylthio tetrazole (PMB-ST) under dual acid-base activation, SR Kotturi, JS Tan and MJ Lear*, Tetrahedron Lett. 2009, 50, 5267-5269.

Stereocontrolled entry to the tricyclo[3.3.0]oxoheptane core of bielschowskysin by a [2+2] cycloaddition of an allene-butenolide, R Miao, SG Gramani, MJ Lear*, Tetrahedron Lett. 2009, 50, 1731-1733.

Singapore R&D and Globetrotting, MJ Lear* et al. Biotech. J. 2009, 4 (2), 179-185 (Biotech Highlight, dedicated to 80th Anniversary of NUS Science in Singapore)

Identification of the binding of sceptrin to MreB via a bidirectional affinity protocol, AD Rodriguez*, MJ Lear*, JJ La Clair*,. J. Am. Chem. Soc. 2008, 130, 7256-7258.

Synthesis of the Entire Carbon Framework of the Kedarcidin Chromophore Aglycon F Yoshimura, MJ Lear*, I Ohashi, Y Koyama, M Hirama*, Chem. Commun. 2007, (29), 3057-3059.

Y. Koyama, M. J. Lear, F. Yoshimura, I. Ohashi, T. Mashimo, M. Hirama "Efficient Construction of the Kedarcidin Chromophore Ansamacrolide", Org. Lett. 2005, 7, 267-270.

T. Usuki, T. Mita, M. J. Lear, P. Das, K. Akiyama, F. Yoshimura, M. Inoue, S. Tero-Kubota, M. Hirama "Spin-Trapping of ¹³C-Labeled p-Benzynes, Generated by Masamune-Bergman Cyclization of Bicyclic Nine-Membered Enediynes", Angew. Chem., Int. Ed. 2004, 43 (6), 5249-5253.

I. Ohashi, M. J. Lear, F. Yoshimura, and M. Hirama "Use of Polystyrene-supported DBU in the Synthesis and a-Selective Glycosylation Study of the Highly Unstable Schmidt Donor of L-Kedarosamine", Org. Lett. 2004, 6, 719-722.

P. Das, T. Mita, M. J. Lear and M. Hirama "Synthesis of ¹³C-labelled, Bicyclic Mimetics of Natural Enediynes", Chem. Commun. 2002, 2624-2625.

S. Kobayashi, S. Ashizawa, Y. Takahashi, Y. Suigura, M. Nagaoka, M. J. Lear and M. Hirama "The First Total Synthesis of N1999-A2: Absolute Stereochemistry and Stereochemical Implications into DNA Cleavage", J. Am. Chem. Soc. 2001, 123 (45), 11294-11295.

M. J. Lear, F. Yoshimura, and M. Hirama "A Direct and Efficient a-Selective Glycosylation Protocol for the Kedarcidin Sugar, L-Mycarose: AgPF₆ as a Remarkable Activator of 2-deoxythioglycosides", Angew. Chem., Int. Ed. 2001, 40 (5), 946-949.