I= STUDIES IN THE CHEMICAL CONSTITUENTS OF PLUMERIA OBTUSA AND STRUCTURE AND ACTIVITY RELATIONSHIP STUDIES IN THE HARMINE SERIES OF ALKALOIDS
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Title of Thesis
STUDIES IN THE CHEMICAL CONSTITUENTS OF PLUMERIA OBTUSA AND STRUCTURE AND ACTIVITY RELATIONSHIP STUDIES IN THE HARMINE SERIES OF ALKALOIDS

Author(s)
Akhtar Naeed
Institute/University/Department Details
University of Karachi
Session
1991
Subject
Chemistry
Number of Pages
218
Keywords (Extracted from title, table of contents and abstract of thesis)
plumeria obtusa, harmine series, alkaloids, nitroharmaline, nitrotetrahydroharmine

Abstract
The work embodied in the present thesis consists of two parts. Part A describes the phytochemical studies in the chemical constituents of plumeria otusa and part B deals with the structure and activity relationship studies in the harmine series of alkaloids.

PART A The neutral and the acidic fractions obtained on work-up (scheme i) of the methanolic extract of fresh,underied and uncrushed leaves of plumeria obtuse (Apocynacease) were subjected to chemical investigations . The neutral fraction was divided into petrol soluble (N-1), petrol EtOAc (7.3) soluble (N-2) petrol. EtOAo(1:1) soluble(N.3) and petrol EtOAc(1:1) insoluble (N-4) fractions (Scheme I and ii) Work on the neutral fraction N-2 led to the isolation of a newlupane triterpenoid (1) along with the five known (2.6)compounds noted below, which are reported for the first time from this source.

Obtusalin (1) Betutinic acid (2) Oleanolic acid (3) Ursolic acid (4) Kaneroside (5) Oleandrin(6)

The neutral fraction N-3 afforded ten new compounds (11-13,15-19,22,23) besides eight known compounds (7-10,14,20,21,24) isolated for the first time from this species :

a-Amyrin (7) Neriucoumaric acid (8) isoneriucoumaric acid (9) Alphitolic acid (10) Obtusin (11) Oytusinin(12) Obtusllin (13) 3b.23-Dihydroxyurs 12-en.28 oic acid (14) Obtusidin (15) Obtusidin (16) Obtusidin (17) Obtusidin (18) Obtusidin (19) 27.p-Z.Coumaroytoxyursolic acid (20) 27.p-E.Coumaroytoxyursolic acid (21) Coumarobtusanoic acid (22) Coumarobtusane (23) Oleanonic acid (24)

The investigation of the neutral fraction N-4 resulted in the isolation of a new compound (27) in addition to five known compounds (4,25,26,28,29) reported for the first time from this species. It may be noted that compound 4 was also obtained from fraction N-2, however its yield was greater in fraction N-4 (vide Experimental).

iUrsolic acid (4) iiPlumierde (25) iiiMethyl.p-E-coumarate (26) ivObtusilic acid (27) vPlumieride p.Z-coumarates (28) viPlumieride p.E-coumarates (29)

Phytochemical investigation on the acidic fraction (Scheme ii) of the methanoltic extract of the leaves led to the isolation of two new indoids (31,32) and a known coumarin (30)

Scopoletin (30) 6-0.Acetylptumieride p.E coumrate (31) 6-0.Acetylptumieride p-Z-coumarate (22) PART B

This part of the thesis deals with the structure and activity relationship studies in the harmine series of bases leading to the synthesis of thirteen new B-carboline derivatives (4-7,16-19,21-24,26) and four new tryptamine derivatives (10-13) alongwith several known compounds.The antibacterial activity (Table 6, Table 11 and Table 12) of these compounds and effect on CNS was also determined.

4-Acetyl-11. methoxy 3 methyiene-12 nitro 3,4,5,6 tetrahydro B-carboline (4) 4-Benzyle-11-methoyxoy 3-methylene-12 nitro 3,4,5,6 tetrahydro B-carboline (5) 4-Cinnamoyl-11 methoxy-3-methylene-12 nitro 3,4,5,6-tetrahydro B-carboline (6) 4-Benzenesulfonyl-11 methoxy 3-methylene 12-nitro-3,4,5,6 tetrahydro B-carboline (7) 3-(2-Acetamidoethyl) 2-acetyl-7-methoxy-8-nitroindole (10) 2-Acetyle 3-(2-benzamidoethyl)7 methoxy 8 nitroindole (11) 2-Acetyl-3(2-cinnamidoethyl)7-methoxy-8 nitroindole (12) 2-Acetyl-3(2-benzenesulfonamidoethyl)7-methoxy-8-nitroindole (13) 4-Amyl-11 methoxy 3 methyl-12-nitro-3,4,5,6-tetrahydro-B-carboline (16) 4=Butyl-11-methoxy 3-methyl-12-nitro-3,4,5,6-tetrahydro-B-carboline (17) 11-Methoxy-3 methyl-12 nitro-4 propyl-3,4,5,6-tetrahydro-B-carboline(18) 4-Ethyl-11-methoxy-3-methyl-12-nitro-3,4,5,6-tetrahydro-B-carboline (19) 4-Allyl-11-methoxy-3-methyl-12-nitro-3,4,5,6-tetrahydro-B-carboline (21) 4-Benzyl-11-methoxy-3-methyl-12-nitro-3,4,5,6-tetrahydro-B-carboline (22) 11-methoxy-3-methyl-12-nitro-4(p-nitrobenzyl)3,4,5,6-tetrahydro-B-carboline (24) 1-Methoxy-3-methyl-12-nitro,3,4,5,6.tetrahydro-4(3,4,5-Trimethoxybenzoyl)B-carboline (26) Extensive spectroscopic techniques such as EIMS,FDMS,FABMS,HRMS UV,IR,1H,and 13C-NMR (BB.DEPT)2D-NMR(COSY-45 NOESY,HeteroCOSY J-resolved) and chemical reactions were employed to elucidate the structures of the compounds noted in Part Aand B.

The introduction of part A and B provides a review of the earlier contribution made in the chemistry and pharmacoloby of the genus plumeria and the plant peganum harmala respectively. The biosynthesis of terpenoids with particular reference to monoterpenoids (iridoids) and pentacyclic triterpenoids has also been described.

The work emobided in the present thesis has resulted in ten research papers as listed in the list of publications.

Download Full Thesis
1289.2 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
325.79 KB
2 1 Part A : Studies In The Chemical Constituents Of Plumeria Obtusa 10
803.84 KB
  1.1 Introduction 44
  1.2 Structural Studies 65
  1.3 Experimental 105
  1.4 References 152
3 2 Part B: Structure And Activity Relationship Studies In The Harmine Series Of Alkaloids 155
347.32 KB
  2.1 Introduction 161
  2.2 Discussion 166
  2.3 Studies In Nitroharmaline And Its Derivatives 167
  2.4 Studies In Nitrotetratrhydroharmine And Its Derivatives 169
  2.5 Experimental 172
  2.6 Derivatives Of Nitroharmaline 173
  2.7 Derivatives Of Nitrotetrahydroharmine 185
  2.8 References 199
4 3 Appendix 209
58.61 KB
  3.1 List Of Tables (Part-A 210
  3.2 List Of Tables (Part-B ) 212
  3.3 List Of New Substances (Part –A ) 213
  3.4 List Of New Substances (Part-B ) 215
  3.5 List Of Publications 217
  3.6 VITA 218