新反応設計と創薬合成への展開

抄録

This review summarizes selected 5 researches fitted to the present title : 1) the synthesis of 1α-hydroxyvitamin D₃, 2) the synthesis of cis-2-cyclopentene-1, 4-diol, 3) the photochemical methods for the cyclobutane annelation to heteroaromatic compounds and for β-lactam synthesis, 4) the novel total synthetic method of modified nucleosides (e.g. C-nucleoside, N-nucleoside, and their carbocyclic derivatives) and its application to the synthesis of (-)-BCA [1R, 4S, 5R-(4, 5-bishydroxymethylcyclopent-2-en-1-yl)-9H-adenine] having anti-HIV activity, and 5) the creation of chiral 1, 3-dihetero six-membered ring compounds as novel synthetic intermediates for enantiomerically pure compounds. All the mothods described are practicable (e.g. easy to handle, applicable to large scale preparation, and wide applicability). Among researches 4 and 5, the followings are notable achivements. For 4, BCA is the first nucleoside analog having non-natural sugar moiety. The use of di-l-menthylacetoxymethylenemalonates as dienophiles has offered new cooperative concept in asymmetric Diels-Alder reactions. Reductive retrograde aldol reaction and sodium borohydride-mediated amide bond cleavage reactions developed in this study have been shown to have wide applicability. For 5, several chiral dihetero six-membered compounds (e.g. 1, 3-dioxin-4-ones, 1, 3-dioxane-4, 6-diones, and 1, 3-oxazine-4, 6-diones) have been synthesized and used successfully for the synthesis of a variety of biologically active compounds (e.g. iridoids, Corey lactone, carbocyclic C-nucleoside, etc.). New proposal involving n-σ^* interaction has been put forward to account for the boat conformation of 1, 3-oxazine-4, 6-diones.