The chemistry of fullerenes has expanded very rapidly in recent years. Since C60 possesses considerably high electron affinity and low ionization potential, this molecule shows a high reactivity to organic reagents to give a variety of adducts. This review summarizes six types of reactions of C60, i.e., cycloadditions, ionic additions, radical additions, halogenations, hydrogenations, and transition-metal-complex formations. The cycloadditions of C60 have been studied very extensively to produce numbers of fullerenes with various substituents. Therefore, these reactions have been classified into [1+2]-, [2+2]-, [3+2]-, [4+2] cycloadditions and the ene reaction. In addition to the reactions of C60, some reactions of C70 have been described.
“Halocarbocyclization reaction”, which involves intramolecular attack of a carbon nucleophile on a double bond activated by an electrophilic halogenating reagent, has so far been uncommon. We report here that “iodocarbocyclization reaction” of alkenyl or alkynylmalonate derivatives proceeded in good yields in the presence of Ti(OR)4 and I2 to give cyclized products in regio- and stereocontrolled manner. The diastereoselective iodocarbocyclization with 4-pentenylmalonate derivatives having a chiral center at the 2 or 3 position and allyl-malonate having a chiral auxiliary in ester part have also been investigated. Futhermore, the reaction of 4-pentenylmalonates using a catalytic amount of a chiral titanium alkoxide in the presence of I2 and 2, 6-dimethoxypyridine proceeded with high enantioselectivity to give good yields of cyclopentane derivatives. The origin of enantioselectivity in this catalytic asymmetric reaction is also described.
A novel method for the stereoselective synthesis of nucleoside derivatives was developed by using the N-bromosuccinimide (NBS) -promoted coupling reaction of thioglycosides with silylated nucleoside bases. The following features were found through this study. (1) 2′-Deoxy-β-D-threo-pentofuranosyl nucleosides, which can be utilized as synthetic intermediates of 3′-substituted 2′, 3′-dideoxynucleosides such as AZT, were synthesized with high stereoselectivity starting from the 3, 5- O-isopropylidene derivative of the corresponding thioglycoside. (2) The reaction of 3, 5-di-O-triisopropylsilyl-2-deoxy-1-thio-D-ribofuranoside proceeded in an α-anomer-selective fashion to afford 2′-deoxy-α-ribonucleosides. (3) In the synthesis of 2′, 3′-dideoxynucleosides, the flanomers were predominatly obtained by lowering the reaction temperature. (4) When various O-benzylated 1-thioglycosides, derived from some hexoses and pentoses, were used under the NBS-promoted coupling conditions, 1, 2-cis-N-glycosides were obtained stereoselectively in every case. Finally, the reaction mechanism for the stereoselective coupling was discussed. We assumed intimate ion pair intermediates consisting of oxonium ions, derived from thioglycosides, and imide ion derived from NBS. An SN2 type attack of nucleoside bases would take place against the sterically favored intermediates to produce nucleoside derivatives bearing the observed stereochemistry at the anomeric positions.
Active forms of vitamin D derivatives in addition to the traditional role in calcium homeostasis play an role in cellar differentiation. The hydroxylation at C-1α-position of vitamin D molecule is essential to elicit the physiological activities. We have developed a new method for the selective 1α-hydroxylation process in the steroidal molecule via enol esterification rearrangement of the 1, 4, 6-trien-3-ones. This review deals with the syntheses of important intermediates for the preparation of active forms of vitamin D and their conversion into the active forms of vitamin D. The steroidal synthon, 1α, 3β-dihydroxy-5, 7-choladiene derivatives obtained from ergosterol or stigmasterol was converted into the various active forms of vitamin D compounds by coupling with phenylsulfonyl derivatives. Similar treatment of pregnenolone afforded (20R and 20S)-1α, 3β-dihydroxy-5, 7-pregnadiene derivatives. According to the procedure described here, 1α-hydroxy and 1 a, 25-dihydroxyvitamin D2, D3, D4, and D7, 24-epi-1α, 25-dihydroxyvitamin D2, 1α, 24dihydroxyvitamin D3, 24, 24-dihomo-1α, 25-dihydroxyvitamin D3 and 1α, 25-dihydroxy-2β-(3-hydroxypropoxy) vitamin D3 were synthesized.
The renin-angiotensin system (RAS) plays an important role in blood pressure regulation and electrolyte homeostasis. Angiotensin II (A II) is the principal active hormone of this system and blockade of the action of A II has been a target for development of novel antihypertensive agents. In the latter half of 1970's, imidazoleacetic acid derivatives were synthesized and discovered to be the first nonpeptide A II antagonists. Structure-activity relationship study of these compounds revealed that CV-2961 (17) had fairly strong A II receptor antagonistic activity. This finding prompted many researchers to develop more potent A II antagonists and led to the discovery of DuP 753 (Losartan) by Du Pont. Further investigation on various heterocycles related to imidazole culminated in the creation of novel diacidic benzimidazole derivatives, CV-11194 (34) and 11974 (Candesartan: 36). A series of ester prodrugs of these compounds was prepared in attempt to improve oral bioavailability. One of the prodrugs thus obtained, TCV-116 (1 : Candesartan cilexetil) showed orally active, highly potent and long-lasting antihypertensive effect in several hypertensive animal models and is under clinical trials. The history of these researches, especially chemical aspect, will be presented.
It is very important to make available methods for the study of molecules within biomembranes : this is necessary in particular to define the topography of membrane-bound proteins, sterols, ubiquinones, carotenoids, etc Khorana, Breslow and others have tried to use, for this goal, probes consisting of a phospholipid or an amphiphile bearing a photosensitive group, in the hope that irradiation of membranes containing them would lead to labelling at a definite level inside the bilayer ; their results have been uniformly disappointing, as the labelling is not at all specific, due to the extensive disorder of the phospholipidic matrix. We have conceived and synthesized a novel type of transmembrane probe 1a, which is shown by 2H NMR and DSC studies to possess favourable physico-chemical properties for membrane topographical studies. It was also shown to be remarkably selective for attack of membrane components near the middle of the bilayer, due to its transbilayer construction and to the concomitant use of cholesterol to improve the order of the lipid chains of the membrane : the myristoyl chains functionalized at C-11, 12 and 13 positions covered 95% of total photolabelled myristates, and cholesterol was principally functionalized at the C-25 position on the side-chain. This indicates the formation of a highly ordered bilayer structure and proved directly the perpendicular orientation of cholesterol to the membrane plane with its chain terminal buried in the middle of the membrane. However, it remained necessary to check whether the addition of cholesterol, a normal constituent of biomembranes, would not, by itself, improve the selectivity of “half-probes” similar to those of Khorana and of Breslow. This is in-deed the case. The new photolabelling systems described here should be useful for the study of the topography of proteins and other constituents in membranes.