Synthetic studies in terpenoids.

Abstract

The thesis entitled "Synthetic Studies in Terpenoids" consists of two parts. The first and major part is devoted to terpenoid synthesis. In this, the synthesis of nine naturally occurring sesquiterpenoids, viz., (+)-nuciferol, ar-dihydro-turmerone, (+)-calamenene, (+)-trans-atlantone, 7-hydroxycalamenene, 7-hydroxycadalene, 7-hydroxycalamenal, 7-hydroxycadalenaI and mansonone C and three sesquiterpenoid analogues of biogenetic interest are reported. Four of the above naturally occurring sesquiterpenoids are synthesised for the first time, the rest obtained by independent syntheses mostly by terpenoid intertransformation. The second part gives an account of a few miscellaneous investigations, two of them having a bearing on reactions of terpenoids and terpenoid intermediates. PART I is divided into seven chapters (1 to 7). Chapter 1 gives a brief review of the chemistry of ar-turmerone, turmerone and ar-dihydro-turmerone covering isolation, significant physicochemical data, structure determination, earlier synthesis, biogenesis and applications, synthetic and commercial, if any. In Chapter 2, preparation of (S)-(+)-ar-curcumene from (S)-(+)-ar-turmerone and its conversion to (S)-(+)-(E)-nuciferol are described. An independent total synthesis of (+)-ar-curcumene is also included. Chapter 3 describes the synthesis of ar-dihydro-turmerone from curcumic acid (synthetically prepared). This sesquiterpenoid ketone has been converted to (+)-calamenene. The absolute configuration of optically active calamenenes (containing two asymmetric centres) is discussed and an account of the preparation of (+)-calamenene from (+)-ar-turmerone together with a discussion of the stereochemical outcome of this conversion is given. Transformation of ar-dihydro-turmerone to 1,5-dimethyl-3-isobutylindane which can be regarded as a cyclomer of calamenene and ar-himachalene is described after giving a brief account of other naturally occurring isoprenoid indanes in relation to their biogenetic origin. Chapter 4 gives the synthesis of two biogenetically interesting dehydro derivatives of ar-turmerone, viz., ar-trans-isoturmerone and ar-trans-atlantone. The latter compound is also related to trans-atlantone. In Chapter 5, after giving an account of the isolation and structure determination of (+)-trans-atlantone, its synthesis for the first time starting from (+)-limonene via its carbon tetrachloride adduct is discussed. This approach incidentally enables the fixing of the absolute configuration of the natural product. The hydrolysis product of the carbon tetrachloride-limonene adduct (limonene-8-carboxylic acid) is also a natural product. Chapter 6 contains an account of the synthesis and facile elaboration of 7-methoxycalamenal to four phenolic sesquiterpenoids, 7-hydroxycalamenene, 7-hydroxycadalene, 7-hydroxycalamenal and 7-hydroxycadalenaI. In Chapter 7, the preparation of mansonone C from 7-hydroxycadalene and 7-hydroxycalamenene is described. PART II is divided into four chapters (8 to 11). Chapter 8 deals with the structure establishment of a non-ketonic acid obtained on alkali treatment of 6-methyl-2-(4-cyanocyclohex-3-enyl)heptan-4-one used earlier in the synthesis of todomatuic acid and juvabione as 1-methyl-3-isobutylhydrind-3(3a),4-diene-5-carboxylic acid and its conversion to 1,5-dimethyl-3-isobutylindane. In Chapter 9, the formation of 2-isopropylidene-4-methyl-??-tetrahydroindanone-7-carboxylic acid in the aluminium chloride catalysed Diels-Alder addition of 3-trans-ocimene to maleic anhydride by an intramolecular acylation is described. In Chapter 10, evidence is provided for the formation of 4-methyl-2,4-di-(2-carboxyphenyl)pent-1-ene as the predominant isomer in the acid catalysed dimerisation of ?-(1-hydroxy-1-methylethyl)benzoic acid. Chapter 11 contains a safe and convenient method of preparation of lithium amalgam. Reprints of six publications comprising the work embodied in the thesis are appended.