Research Areas

(a) Isolation and Structure Elucidation of Bioactive Compounds

Atta-ur-Rahman's work on the isolation and structure elucidation of bioactive substances from medicinal plants as well as marine plants and animals has resulted in the discovery of several hundred new/novel natural products many of which have exhibited exciting biological activities including anti-oxidant, anti-epileptic, anti-leishmania, anti-AIDS, immunomodulating, anti-asthamatic, analgesic, nematicidal and anti-cancer activities. These are exemplified by researches on cholinesterase - inhibiting steroidal alkaloids from Sarcocca saligna with potential applications in Alzheimer's disease [Helv. Chim. Acta, 87, 439-448 (2004)], new α-glucosidase inhibitors from Ferula mongolica, [Helv. Chim. Acta., 84, 2409 (2001)], anti-fungal diterpenoid alkaloids from Delphinium denudatum, [J.Nat. Prod.,60, 472-474 (1997)], anti-bacterial steroidal alkaloids from Sarcocca saligna, [J. Nat. Prod.,61, 202-206 (1998)] etc. A number of binary and dimeric alkaloids have also been reported from terrestrial and marine sources.

(b) Development of New Methods 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, [J. Am. Chem. Soc.,115, 12533-12544 (1993)]. The method was extended to peptides, [Nat. Prod. Lett.,13(2), 131 (1999)]. He has also developed correlations between structures of steroidal alkaloids with their specific rotations, [Tetrahedron,42(20), 5747 (1986)].

(c) Synthetic Transformations of Biologically and Biosynthetically Interesting Compounds

An intriguing challenge in the late 60's / early 70’s was the biosynthetic origin of the tetracyclic indole moiety of vinblastine/vincristine, anti-tumor alkaloids of Catharanthus roseus (marketed by Ely Lilly & Co. for acute leukaemia in children, Hodgkins 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 [Pak. J. Sci. Ind. Res., 14(6), 487 (1971)]. This approach (i.e. using catharanthine as the precursor) became the preferred procedure for subsequent synthetic approaches to these anti-leukemic alkaloids. A biomimetic synthesis of vinblastine was subsequently developed and patented, [Pakistan Patent No. 126852, dated 14-2-1978]. Interesting synthetic transformations /rearrangements discovered include the high yield fragmentation of the hexacyclic 16-epi-19-S-vindolinine to a tricyclic indole, [Heterocycles, 20(1), 59 (1983)]. The work of the Nobel Laureate Sir Robert Robinson & co-workers on the chemistry of harmaline was also corrected and it was shown that an interesting ring fragmentation occurs with Nb-acetyl harmaline under certain conditions, [J. Chem. Soc. Perkin Trans. I., 736 (1972)] and (No. 153), [J. Chem. Soc. Perkin Trans. I., (5), 731 (1972)]; [Chem. Abs., 76, 127211u (1972)].