Enantioselective synthesis of (R)- and (S)- d - octalactone and their effects on Glossina morsitans morsitans host seeking behaviour
Mwangi, Martin Thuo
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African trypanosomosis is a complex disease of man and livestock that smoulders silently in the rural sub-Saharan Africa wrecking great havoc to the poor communities and causing loss of life, properties, and migration from villages or regions. To the victims, it causes a reversal of the circardian rhythms (sleep-wake cycle) and hormonal secretion. About 55 million people, 56 million cattle, 32 million goats and sheep and >260 million other small ruminants are at risk of this disease in Africa. Tsetse flies are its primary cyclic vectors thus a threat in >40 countries south of the Sahara. The economic effects of trypanosomosis places it second to malaria among vector borne diseases of importance to Africa. Thus, the OAU dedicated year 2001 to the control of the tsetse fly. The use of semiochemical-derived products in disease vector control is environmentally friendly and has low risks of resistance development. Unfortunately, semiochemicals occur in minute quantities in nature thus cheap synthetic samples become handy tool in their use. - Octalactone was isolated from a non-preferred host of the tsetse fly, the waterbuck, among other electrophysiologically active compounds. The electrophysiological activity studies and synthesis of the racemic mixture was done. Behavioural bioassay of the racemate was not done nor were the enantiomers synthesized separately. he current work involved the enantioselective synthesis of - octalactone and investigation of an economically viable route to the active isomer (s). We have discovered an efficient and economical synthetic route to the racemate and both isomers. The CIPE is asymmetric induction reactions were exploited efficiently in the chiral synthesis. Absolute configuration was assigned based on Cram's rule, CIPE and basic chemical thermodynamic theory. The bioassays of the synthetic products using 3-day starved teneral tsetse flies (G. morsitan) revealed that stereochemistry has no role to play in the repellent properties of this lactone (no stereospecific antennal responses). The compounds were identified by conventional analytical methods. Results indicate that the molecule is a repellent with a high potential in tsetse fly control. From this work, a new route to - lactones utilizing organomettalic reagents is being reported for the first time.