Professor Atta-ur-Rahman: towering scientific achievements

Prof. Atta-ur-Rahman's scientific contributions are internationally recognised and widely appreciated. He is one of the most prominent natural product chemists of the twentieth century. His work is characterised by its originality and depth. His contributions in the field of natural products chemistry and NMR spectroscopy have expanded the boundaries of these sciences and played a crucial role in attracting young talents. He has been active in the development of new medicinal agents, and the isolation, structure elucidation and synthesis of several hundred natural products. With over 900 research publications in top international science journals and 130 books edited, written and published internationally, Prof. Atta-ur-Rahman is well known in his field for his prolific and excellent research publications.

Prof. Atta-ur-Rahman was elected as a Fellow of the Royal Society on 14 July 2006. He is one of very few scientists from the Islamic world to have been elected and the first in the 350-year history of the Royal Society to be elected in recognition of research work carried out within an Islamic country. The Royal Society was established in London in the mid-1600s under Royal Charter. Since then it has had some of the most eminent scientists of the world among its Fellows, including over 80 Nobel Laureates and such luminaries as Isaac Newton, Charles Darwin and Albert Einstein. He is the first resident Pakistani scientist to be honoured by Cambridge University with a D.Sc degree in October 1987. He is also the second Pakistani scientist to be elected as fellow of three major academies including the Third World Academy of Sciences, Islamic Academy of Sciences and Pakistan Academy of Sciences. He is also serving as the President of the Pakistan Academy of Sciences. Prof. Rahman is the first scientist from the Muslim world to have won the prestigious UNESCO Science Prize (1999) in the 35-year history of the Prize. He was elected Honorary Life Fellow of Kings College, Cambridge University, UK, in 2007. Prof. Atta-ur-Rahman was awarded the TWAS Prize for Institution Building in Durban, South Africa, in October 2009 in recognition of his contributions to bringing about revolutionary changes in the higher education sector in Pakistan. The Austrian government also honoured him with its highest civil award (the ‘Grosses goldenes Ehrenzeichen am Bande’) in 2007 in recognition of his eminent contributions.

More than 850 publications, 21 international patents and over 130 books published by major international publishers in the USA, Europe and Japan are evidence of his enormous contributions in the field of natural products. Scientifically his research contributions can be classified into the following main areas.

1. Synthesis and synthetic transformations of biologically interesting natural products

The first synthesis of vinblastine, which is among the most important anticancer drugs, was reported by Prof. Atta-ur-Rahman in 1978, patented in the UK, Germany and Pakistan (Atta-ur-Rahman 1976–1978). One year later, an identical synthetic route was published by a French group in Journal of American Chemical Society, 101:2243 (1979). He continued the synthetic studies on indole alkaloids, added several new methodologies and new indole derivatives and published dozens of research papers in this field of research during 1980–1988. He has also developed efficient methods for the large-scale isolation of vinblastine and vindol from the leaves of Catharanthus roseus, which is an important anticancer natural product (Atta-ur-Rahman et al., 1980, 1983a, 1983b; Atta-ur-Rahman et al. 1986).

An intriguing challenge in the late 1960s and early 1970s was the biosynthetic origin of the tetracyclic indole moiety of vinblastine/vincristine, anti-tumour alkaloids of C. roseus (marketed by Eli Lilly & Co. for acute leukaemia in children, Hodgkin's disease and other cancers under the trade names of ‘Velbe’ and ‘Oncovin’). It was believed that such tetracyclic indoles would exist in the plant but no such tetracyclic indoles had been isolated. Atta-ur-Rahman first proposed that vinblastine may arise from a pentacyclic precursor alkaloid, such as catharanthine. He demonstrated the conversion of pentacyclic catharanthine into the tetracyclic ‘cleavamine’ moiety in high yields, leading to the first synthetic vinblastine derivative (Atta-ur-Rahman et al. 1971). This approach (i.e. using catharanthine as the precursor) became the preferred procedure for subsequent synthetic approaches to these anti-leukaemic alkaloids. A biomimetic synthesis of vinblastine was subsequently developed and patented (Atta-ur-Rahman 1978). Interesting synthetic transformations/rearrangements were discovered including the high yield fragmentation of the hexacyclic 16-epi-19-S-vindolinine to a tricyclic indole (Atta-ur-Rahman et al. 1983a, 1983b).

The work of the Nobel Laureate Sir Robert Robinson and co-workers on the chemistry of harmaline was also corrected and it was shown that an interesting ring fragmentation occurs with N _b-acetyl harmaline under certain conditions (Atta-ur-Rahman 1972a, 1972b).

2. Isolation and structural studies on bioactive compounds

In the field of isolation and structural studies of natural products, Prof. Atta-ur-Rahman has isolated and established structures of hundreds of new natural products from a variety of sources including medicinal plants, marine invertebrates, sea alga and micro-organisms. His work on the isolation, structure elucidation and biological studies of steroidal, indole and isoquinoline alkaloids, withanolides, physalins and many other important classes of natural products has been widely recognised for originality and significance. These several hundred new/novel natural products, isolated by Prof. Atta-ur-Rahman and co-workers, have exhibited exciting biological activities including anti-oxidant, anti-leishmanial, anti-AIDS, immunomodulating, anti-asthmatic, analgesic, nematicidal and anti-cancer activities. Some of his recent contributions in the field of structural studies are cholinesterase – inhibiting steroidal alkaloids from Sarcococca saligna with potential applications in Alzheimer's disease (Atta-ur-Rahman et al. 2004), new α-glucosidase inhibitors from Ferula mongolica (Atta-ur-Rahman et al. 2001), anti-fungal diterpenoid alkaloids from Delphinium denudatum (Atta-ur-Rahman et al. 1997), antibacterial steroidal alkaloids from S. saligna (Atta-ur-Rahman et al. 1998), antiepileptic secondary metabolites from Delphinium species (Raza et al. 2003; Atta-ur-Rahman et al. 2008), discovery of anti-leishmanial compounds and clinical trials on the most potent compound and/or extracts (Choudhary et al. 2005; Atta-ur-Rahman et al. 2012). Isomeric mixture of isoxylitones A and B, obtained from a medicinal plant D. denudatum, is in first phase of clinical trials in North America. A number of binary and dimeric alkaloids have also been reported from terrestrial and marine sources.

3. Development of new methods and applications of NMR techniques for structure elucidation

A new convenient method was developed for the determination of absolute configurations of chiral carboxylic acids, α-amino acids, amino alcohols, polynucleic acids and ephedrine isomers by partially or totally restricting their conformational flexibility through complexation with trinuclear metal complexes, [M₃O(O₂CCH₃)₆L₃] ⁿ where M = Fe, Cr, Mn, Rh, Ru, etc., L = water or pyridine and n = 0 or 1 (Ahmed et al. 1993). The method was extended to peptides (Ahmed & Atta-ur-Rahman 1999). He has also developed correlations between structures of steroidal alkaloids with their specific rotations (Choudhary et al. 1986).

Based on his interests in modern pulse NMR spectroscopy, he has contributed several papers related to the applications of new NMR techniques in the structure elucidation of novel natural products.

In addition to his excellent scientific achievements and globally recognised leadership for the promotion of science, technology, higher education and information technology in Pakistan and the developing world (Brumfiel & Inman 2010, Nature editorials 2007 & 2009), in my opinion, the most notable contribution of Prof. Atta-ur-Rahman is the development of the H.E.J. Research Institute of Chemistry against all odds. The H.E.J. Research Institute of Chemistry is now the largest academic research Institution in Pakistan with over 500 Ph.D. students from every corner of Pakistan and many other countries, working on frontier aspects of chemistry and biochemistry. The institute is regarded as one of the finest and well-equipped research institutions anywhere in the world in the field of natural product and medicinal chemistry. The man who established this great institution almost single-handedly, and is still serving this largest and most productive academic and scientific establishment of Pakistan as Chief Patron, is indeed the busiest person I have ever seen in my life. The scientific contributions of Prof. Atta-ur-Rahman, FRS, and his tremendous services for the promotion of science and technology in Pakistan and other developing countries will always be cherished and remembered.

His towering personality, his gentle nature and, most importantly, mentoring of generations of young chemists from all around the world are the attributes of an ideal scientist and an excellent human being.