Vinylic nucleophilic substitution via a concerted bimolecular mechanism (SNV 2), which has long been rejected as a possible pathway, has recently been found to be feasible both theoretically and experimentally. Two SNV 2 mechanisms are possible : one is designated as SNVσ where nucleophilic attack takes place in a molecular plane at the σ* orbital resulting in inversion of configuration, while the other as SNVπ which involves out-of-plane π* attack of a nucleophile leading to stereochemical retention. Both modes of the concerted SNV 2 reactions were found for vinyl iodonium salts, and detailed mechanistic investigations are summarized. Intramolecular SNVσ reactions were more often observed, and applied to some synthesis of cyclic compounds. Those observations are rationalized by high level ab initio MO calculations.
This paper describes efficient synthesis, chemical behaviors, and biological activities of cyclic bis (3'-5') diguanylic acid (c-di-GMP) and its analogs, including cyclic bis (3'-5') guanylic-inosinic acid (c-GpIp), cyclic bis (3'-5') guanylic-adenylic acid (c-GpAp), and bis (3'-5') diguanylic acid monophosphorothioate (c-GpGps). c-di-GMP was synthesized via two methods shown in Scheme 1 and Scheme 2. Between the two methods, that shown in Scheme 2 is more effective, particularly, for large-scale (gram-scale) synthesis to obtain the target compound in a high yield. While, c-GpIp, c-GpAp, and c-GpGps were synthesized via strategies similar to that of Scheme 2. Studies on chemical behaviors of c-di-GMP indicated that these cyclic dinucleotides exist as the monomers in aprotic solvents such as DMSO. By contrast, it was shown that c-di-GMP smoothly aggregates to form a mixture of many compounds in water, in < 0.9% sodium chloride solutions, in < 100 mM phosphate buffer solutions, and in < 100 mM ammonium acetate buffer solutions. All aggregated compounds smoothly revert to a single compound (probably an aggeregate) by dissolving in a 0.9% sodium chloride solution (a physiological salt solution), a > 100 mM phosphate buffer solution, or a > 100 mM ammonium acetate buffer solution. Biological investigation dis-closed some novel activities of c-di-GMP, such as inhibition of biofilm formation of Staphylococcus aureus, inhibition of basal and growth factor stimulated human colon cancer cell prolifelation, and reduction of the viluence of biofilm-formed Staphylococcus aureus in a mouse model.
A selective nonpeptidic δ opioid receptor agonist TAN-67, (4aS*, 12 aR*) -4 a- (3-hydroxyphenyl) -2-methyl-1, 2, 3, 4, 4 a, 5, 12, 12 a-octahydropyrido [3, 4-b] acridine was designed from the selective δ opioid receptor antagonist NTI on the basis of the message-address concept and the accessory site theory. (-) -TAN-67 is a potent and selective δ1 opioid receptor agonist and showed profound antinociceptive effect, cardioprotective effect, and antiarrhythmic effect. On the contrary, (+) -TAN-67 induced hyperalgesia, which is the opposite effect of the antinociception. Optical resolution of racemic TAN-67 and the synthesis of (4aS*, 8 aR*) -4 a- (3-methoxyphenyl) -2-methyl-6-oxodecahydroisoquinoline, the important intermediate ketone of TAN-67 synthesis were also described.
A micro-scale chemical/CD (FDCD) exciton chirality protocol has been realized for determining the absolute configuration of C=C double bond containing compounds. This method is based on the conversion of the preexisting and/or introduced double bonds into the p-substituted styrenoid chromophores and/or fluorophores via cross olefin metathesis, that function as the new CD and FDCD reporter groups. The method has been applied to a variety of natural and synthetic compounds, i.e., (i) allylic alcohols and amines, (ii) macro-cyclic molecules, (iii) unstable alcohols where acylation by Mosher's acid fail, (iv) chiral molecules bearing no other functional groups than ene moieties, in which other methods are not accessible, (v) substrates bearing the sterically hindered hydroxyls, and (vi) large compounds where two hydroxyls are separated by a long distance. Based on the established method, the configurational assignment of gymnocin-B, a new polyether marine natural product containing 15 contiguous polyether skeleton, has been realized.
vic-Disulfoxides have been recognized as very unstable intermediates in the electrophilic oxidation of disulfides. In 1999, we succeeded in the isolation and structure determination of tetrathiolane 2, 3-dioxide 11, which was the first isolable compound having an-S (O) -S (O) -moiety. After this study, we could prepare 1, 2, 4-trithiolane 1, 2-dioxides 12-14, 7, 8-dithiabicyclo [4.2.1] nona2, 4-diene 7, 8-dioxide 15, and dithiirane 1, 2-dioxide 16. The-S (O) -S (O) -moieties of 11-16 reside in a 5-or 3-membered ring, which should contribute to the stability of vic-disulfoxide bonds. Here we report the syntheses of vic-disulfoxides isolable under ambient conditions and their chemical and physical properties.
We have successfully developed novel electrolytic systems using solid-supported acids and bases. Anodic fluorination of various compounds using KF as a fluorine source and solid-supported acids as a supporting electrolyte was successfully carried out to provide the corresponding fluorinated products in good to excellent yields. On the other hand, anodic methoxylation, anodic acetoxylation, Kolbe electrolysis, and non-Kolbe electrolysis of various compounds using solid-supported bases as a precursor of supporting electrolytes were also conducted to afford the corresponding methoxylated, acetoxylated, Kolbe, and non-Kolbe products in moderate to excellent yields, respectively.
This mini review focuses on current topics on the following two reactions with azido compounds, which have been recently developed in the field of chemical biology; I) triazole synthesis by copper-catalyzed cycloaddition of an azide with an alkyne, II) modified Staudinger reaction, that is, Staudinger ligation.
More than 20, 000 people suffer annually from ciguatera seafood poisoning in tropical and subtropical areas. The principal causative agents, ciguatoxin and its congeners CTX3C and 51-hydroxyCTX3C are extremely potent neurotoxins that bind to voltage-sensitive sodium channels. The extremely limited availability of these ciguatoxins has hampered the detailed biological studies and preparation of anti-ciguatoxin antibodies for detecting these toxins. Therefore the supply of these compounds by the chemical synthesis has been strongly demanded. Furthermore the unique structural features have attracted the attention of the synthetic chemists. This review has briefly focused on the synthetic studies of ciguatoxins in a convergent manner including a total synthesis.