I= STRUCTURAL, SYNTHETIC AND BIOTRANSFORMATION STUDIES OF SOME STEROIDAL ALKALOIDS, STEROIDS AND SESQUITERPENES
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Title of Thesis
STRUCTURAL, SYNTHETIC AND BIOTRANSFORMATION STUDIES OF SOME STEROIDAL ALKALOIDS, STEROIDS AND SESQUITERPENES

Author(s)
Afgan Farooq
Institute/University/Department Details
H.E.J Research Institute of Chemistry/ University of Karachi
Session
1996
Subject
Chemistry
Number of Pages
217
Keywords (Extracted from title, table of contents and abstract of thesis)
steroidal alkaloids, steroids, sesquiterpenes, buxus papillosa, fritillaria imperialis, terpenes, nootkatone, epoxy steroid

Abstract
The thesis describes phytochemical investigations on the roots of Buxus papillosa and bulbs of Fritillaria imperialis to yield new steroidal alkaloids, study of structure-activity relationships of imperialine, synthetic studies on some androstane derivatives and biotransformations of three cytotoxic sesquiterpenes.

Phytochemical investigations on the roots of Buxus papillosa yielded two new steroidal alkaloids, (+)-papillotrienine(121) and Nb-demethylpapillotrienine (125). Phytochemical studies of the bulbs of Fritillaria imperialis of Turkish origin afforded a new anticholinergic steroidal alkaloid, ebeinone (57), four steroidal alkaloids eduardine (138), edpetilidine (139), verticinone (140), and isoverticinone (141) for the first time from this plant and a known steroidal alkaloid, imperiline(152)-----------------------------------------------------------------

Imperialinol (53), 3β-acetoxyimperialine(54) , 3β-propionoxyimperialine (55), and 3β-butyroxyimperialine (56) were prepared from imperialine (52) for establishing structure activity relationships where 3β-propionoxyimperialine (55) exhibited the best anticholinergic activity. -----------------------------------------------

The partial synthesis of some androstane derivatives from commercially available androstane (dehydroisoandrosterone) was completed in the laboratory of Dr: J. R. Hanson. University of Sussex. England. The aim of this work was not only to get new steroids and investigation of new methods of synthesis but also to study the stereoselectivity of the reactions such as nucleophilic displacements. esterifications. allylic oxidations. reductions. epoxidations and halogenations. As a result. eleven new steroids 'were synthesised from a commericiaU1 available steroid. i.e dehydroisoandrosterone(142).

A new three-step methodology for the synthesis of two new steroids 17β-acetoxyandrosta-3.5-dien-7-one (145) and 17β-acetoxyandrosta 3.5-dien-2.7-dione (146) has been investigated where another new steroid. 3β, 17β-di-(trimethylacetoxyandrost-5-ene (144) was also prepared as an intermediate.-------------------------------------------------------

A seven step stereos elective synthesis of an epoxy steroid, 6α,7 α-epoxy-3, 17-di-(trimethyl)acetoxyandrostane(155) has been accomplished. Five new compounds namely 3β,17β-di(trimethyl)acetoxyandrost-5-en-7–one,6α,7β–dihydroxy-3β,17β-di-(trimethyl) acetloxyandrostan (152),6α,7β,17β-trihydroxy-3β(trimethyl) acetoxyandrostane (153) hydroxy-7p-toleuneβ-sulfonoxy-3β,17P-di-(trimethyl)acetoxyandrostane(154)and finally (155)were obtained as a result of this study.

The stereoselective synthesis of 6α, 7β, 17β-trihydroxyandrostane (161) was achieved by a six-step synthetic transformation sequence of dehydroisoandrosterone (142). This resulted in the synthesis of another new steroid namely. 17B-(trimetyl) acetoxyandrostan-5-en (159)

A four-step synthesis of a new halogenated steroid. 3β -meth; mesulfonoxy-5α- hydroxy-7α-bromoandrost -6,7-dione (165) was completed in order to attempt the ring contraction for the synthesis of B-nor steroids which could not be achieved.-------------------------------

Biotransformation studies on three cytotoxic sesquiterpenes afforded nine Interesting chemically inaccessible compounds. Nootkatone (107) afforded 9α-hydroxynootkatone (108) and 11.12-dihydmxynootkatone (109) by fermentation with Cephalosporium aphidicola. Sclareolide (110) gave 3-ketosclareolide (111) 1α,3β-hydroxysclareolide (112), 3β-hydroxysclareolide (113), lα,3β-dihydroxysclareolide (114) and 1α.3β-dihydroxysclareolide (115) by fermentation with Curvularia lunata. 7α-Hydroxyfrullalonide (118) yielded 1l.13-dlhydro-7a-hydroxyfrullanolide (119) and 13-acetyl-7a-hydroxyfrullanolide (120) by fermentation with Aspergillus quadrilineatus while fermentation with Aspergillus niger gave only-------------------------------------------------------------

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S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
98.55 KB
2 1 General Introduction 1
21 KB
3 2 Introduction 4
330.36 KB
  2.1 Steroidal Alkaloids 5
  2.2 Steroids 33
  2.3 Terpenes 36
  2.4 Biotransformations 41
4 3 Results and discussion 47
805.1 KB
  3.1 Structural studies of some steroidal alkaloids 48
  3.2 Synthetic studies of some steroids 92
  3.3 Biotransformations of some sesquiterpenes 112
5 4 Experimental 135
527.92 KB
6 5 References 187
144.69 KB
  5.1 Glossary 195
7 6 Appendix 203
285.8 KB
  6.1 Subject Index 216