| dc.description.abstract | The thesis entitled "Synthetic Studies in Terpenoids" consists of five chapters and embodies accounts of:
(1) a review for the first time of cuparenoid (arylcyclopentane) sesquiterpenes,
(2) a new synthesis of p-cuparenone, a naturally occurring ketone of the arylcyclopentane class of sesquiterpenoids,
(3) the revision of the structure of phenylcamphoric acid, again an interesting arylcyclopentane made nearly seventy-five years ago,
(4) the synthesis of several sesquiterpenoid insect hormone analogues of ar-juvabione, all of which exhibited excellent juvenile hormone activity, and
(5) the synthesis for the first time of xanthorrhizol, a naturally occurring phenolic sesquiterpenoid.
The thesis starts with a review (Chapter 1) of cuparenoid sesquiterpenes belonging to the class of 1-aryl-1,2,2,5-trimethylcyclopentane compounds. Grouped under hydrocarbons, alcohols, aldehydes and ketones, acids, phenols and phenolic ethers and quinones, the chemistry of the individual members of each group is discussed in the order of their occurrence, structure determination, synthesis (where available), and biogenesis. The review is concluded with a short account of the chemistry of the physiologically active trichothecane class of compounds in which the arylcyclopentane skeleton is extensively modified in both the aromatic and the alicyclic rings.
Chapter 2 illustrates a useful approach developed for the building of the aryl-1,2,2-trimethylcyclopentane skeleton, consisting in the intramolecular insertion of a carbenoid derived from a diazoketone into a benzylic C–H bond. The approach is exemplified in the synthesis of p-cuparenone, a constituent from the essential oil from Mayur Pankhi (Thuja orientalis L.). 5,3-Dimethyl-4-p-tolylvaleric acid prepared by Grignard reaction of p-tolylethylmagnesium chloride with isopropylidene cyanoacetate was converted to 1-diazo-4,4-dimethyl-5-p-tolylhexan-2-one which furnished p-cuparenone by intramolecular carbenoid insertion. A brief account of the insertion reactions of carbenoids is also included here.
Chapter 3 describes the reactions of one of the two phenylcamphoric acids obtained from Friedel–Crafts reaction of benzene with camphoric anhydride. The spectral data of the phenylcamphoric acid and its derivatives, in particular the paramagnetic shifts experienced in presence of the shift reagent Eu(fod)? by the cyclopentanone derived from phenylcamphoric acid by Baeyer–Villiger sequence of reactions, led to the assignment of the structure of phenylcamphoric acid as 2,2,3-trimethyl-4-p-phenylcyclopentane-1-carboxylic acid. Arguments based on spectral and chemical evidence in favour of the all-cis stereochemistry for this acid are also discussed.
Chapter 4, which deals with the synthesis of various aromatic analogues of juvabione, is divided into two parts and is prefaced with a short survey on insect juvenile hormone analogues, giving their classification, chemistry, mode of action and structure–activity relationships.
The first part of the chapter describes a simpler alternative synthesis of ar-juvabione employing the versatile synthon, ethyl 3-oxo-5-methylhexanoate. This is followed by an account of the preparation of bisdehydro-ar-juvabione, a compound possessing high juvenile hormone (JH) activity. The first synthesis of dehydro-ar-juvabione is also reported here by carboxylation of ar-norturmerone. It exhibited even higher activity against Dysdercus koenigii compared to ar-juvabione.
The second part of the chapter deals with the synthesis of o- and m-analogues of ar-juvabione and deisopropyl-ar-juvabione using the synthon already mentioned and the appropriate a-arylethyl bromides. During the course of the synthesis of o-ar-juvabione it was found that acid or base hydrolysis of 2-(3-carbethoxy-4-oxo-6-methyl-2-heptyl)benzonitrile gave 5-methylindanone instead of the expected o-ar-todomatuic acid. A mechanism for the indanone ring closure is outlined. It concludes with the preparation of p-carbomethoxyphenyl-5-methylhexan-5-one, which proved to be the most potent in respect of morphogenetic activity.
Chapter 5 describes the synthesis of xanthorrhizol, a phenolic sesquiterpenoid isolated from the rhizomes of Curcuma xanthorrhiza Roxb., used as a drug. 3-Methoxy-4-methylacetophenone was elaborated to methyl 5-(3-methoxy-4-methylphenyl)hexanoate. Grignard reaction on the ester with methylmagnesium iodide followed by dehydration furnished xanthorrhizol methyl ether, which was demethylated to the phenol by heating with methylmagnesium iodide. In this work the novel finding of cyclodehydration (in addition to demethylation) of methoxyaryl-substituted acid to benzocycloheptanone, brought about by pyridine hydrochloride, is also reported.
The material constituting Chapters 2 and 4 of the thesis was presented at the Organic Chemistry symposia held at Madras (1973) and Bombay (1971). Two papers comprising the subject matter of Chapters 3 and 4 have been submitted for publication. The work on juvabione is in press, while that on the synthesis of xanthorrhizol is under preparation for submission for publication. The work on cuparenone has been accepted for publication in J. Chem. Soc. (Perkin Transactions I). | |
