CHEMICAL STUDIES ON THE CONSTITUENTS OF AZADIRACHTA INDICA A. JUSS

Abstract

The work embodied in the present thesis relates to the studies on the chemical constituents of Azadirachta indica and is presented in two parts. Part A describes the isolation and characterization of the chemical constituents of the fresh ripe fruit coats, ripe fruit kernels and the seed oil. Part B involves studies on the structure and activity relationship of new meliacin analogues prepared from epoxyazadiradione and azadiradione the two major constituents of the neem tree. A brief review of the biosynthesis of terpenoids with particular reference to the triterpenoids is also included. PART A The introduction of part A provides a review of the earlier researches on the chemical constituents of A indica, their pharmacological and pesticidal properties, and a brief account of the present work. These studies have led to the isolation and structure elucidation of sixteen new and eight known triterpenoids,and two steroidal glycosides. Identification of four hydrocarbons has also been made through GC/MS. NEW CONSTITUENTS TRITERPENOIDS I)Limocinol(1) II)Limocinone (5) III)Azadirol(12) IV)Naheedin (26) TRINORTRITERPENOID V)Limbonin (17) TETRANORTRITERPENOIDS VI)Limocin A (6) VII)Limocin B (7) VIII) Limocinin (8) IX)Azadironolide (15) X)Isoazadironolide (16) XI)Limbocinin (20) XII) Limbocidin (21) XIII) Mahmoodin (24) OCT ANORTRITERPENOID XIV) 5a-(13aMe)- Androsta-7a.-acetoxy-4,4,B-trimethyl-1, 14-dien-3, 16-dione (desfurano-azadiradione) (9) NONANORTRITERPENOIDS XV) 5a-(13aMe)-Androsta-7a.-acetoxy-17-oxa-4,4,B-trimethyl-1, 14-dien-3, 16-dione (10) XVI) 5a-Androsta-7a.-acetoxy-17-oxa-4,4,B-trimethyl-1, 14-dien-3, 16-dione (11 ) KNOWN CONSTITUENTS I)Azadirone (III) II)Azadiradione (IV) III) Epoxyazadiradione (II) IV) Gedunin (V) V) Kulactone (4) VI) Nimbin(l) VII) Deacelylnimbin (VI) VIII) 17-Hydroxyazadiradione STEROIDAL GLYCOSIDES IX)Stigmasterol glycoside (22) X)Stigmasterol glycoside (23) HYDROCARBONS XI) Icosane XII) Docosane XIII) 2-Methyltricosane XIV) Docosene PART B Hydrolysis of epoxyazadiradione and azadiradione, two major constituents of Azadirachta indica isolatable using simplified procedures (vide experimental) with ethanolic and methanolic potash respectively, led to new meliacin analogues listed below. i)7-Deacetoxy-14-ethoxy-7cl, 15 β.-dihydroxy-14. 15-dihydroazadiradione(28) ii)7-Deacetoxy-7α-hydroxy-15-ethoxyazadiradione (30) iii)7-Deacetoxy-7α-hydroxy- 15-ethoxy-17-epiazadiradione (31) iv) 7-Deacetoxy-7α. 16-dihydroxy-15-ethoxy- Δ16-azadirone (32) v)7-Deacetoxy-7α.5β. 16-trihydroxy-14-ethoxy- 14. 15-dihydro-Δ16 -azadirone (34) vi)17-Epinimbocinol (35) Extensive spectroscopic techniques such as IR, UV,CD, mass, 1H- and 13C-NMA (BB, DEPT), 2D-NMA (COSY-45, NOESY, Hetero COSY, HMQC and INADEQUATE), and chemical reactions were employed to elucidate the structure of all the isolated and synthetic compounds.