A modular and concise total synthesis of (+/-)-daurichromenic acid and analogues, and, A new method for the mild and selective mono-dealkylation of tertiary amines

This thesis consists of two parts. Part One concerns the total synthesis of (+/-)-daurichromenic acid and a series of structural analogues. Daurichromenic acid, a natural product isolated from the leaves and twigs of Rhododendron dauricum, has potent anti-HIV activity. A concise synthetic route was designed whereby the target molecule was prepared in four steps from trans,trans-farnesal, ethyl crotonate and ethyl acetoacetate. Furthermore, the modular nature of the synthetic route allowed for the preparation of a variety of structural analogues of the natural product. Although the overall yield of this route was relatively low, significant quantities of analytically pure materials have been obtained for subsequent biological evaluation.; Two alternative routes were explored in order to circumvent a problematic dehydrogenation/aromatization step encountered in this route. In these instances, attempts were made to install the aromatic ring of the target compound through migration of a carbon-carbon double bond and via a retro-Diels-Alder reaction.; Moreover, a strategy employing a phenylboronic acid-promoted condensation reaction of methyl orsellinate and alpha,beta-unsaturated aldehydes as the key step was also developed. This provided additional access to a series of structural analogues of (+/-)-daurichromenic acid from commercially available starting materials.; In Part Two of the thesis, a new procedure for the mono-dealkylation of tertiary amines is described. Attempted oxidation of a known hydroxy crown ether derivative, 2,3,9,10-dibenzo-6-hydroxy-16-crown-5, under modified Swern conditions resulted in the unexpected formation of a diethylamide as the major reaction product. Based on this initial observation, a novel and facile means was developed for the mono-dealkylation of a series of tertiary amines using a monoester of oxaly1 chloride as the cleaving agent. The experiments also demonstrated that various alkyl groups could be cleaved and the selectivity of the bond breaking process was: benzyl > allyl > methyl > heterocyclic ring.; The chemoselectivity of this new dealkylation procedure was demonstrated by performing the selective removal of the N-benzy1 group of (2S)-1-benzyl-2-[(benzyloxy)methyl]pyrrolidine. The reaction proceeded cleanly and resulted in the isolation of the desired amide product in 83% yield. Subsequent hydrolysis of the amide product afforded (2 S)-2-[(benzyloxy)methyl]pyrrolidine in excellent yield.