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1.
Chem Pharm Bull (Tokyo) ; 69(9): 926-930, 2021.
Article in English | MEDLINE | ID: mdl-34470957

ABSTRACT

Acyclic asymmetric quaternary stereocenters, which are composed of four carbon-carbon bonds, were finely constructed by utilizing a face-selective alkylation of enolate intermediates derived from an asymmetric Michael addition reaction of a chiral lithium amide with trisubstituted (E)-α,ß-unsaturated esters. The present face-selective alkylation was able to employ diverse alkyl halides as an electrophile to afford various Michael adducts having an all-carbon quaternary stereocenter. With regard to the deprotection of the chiral auxiliary, N-iodosuccinimide used in our previous study did not work in the present cases; however, we found that pyridine iodine monochloride in the presence of H2O was effective to remove the bornyl group and the benzyl group on the amino group to provide the ß-amino ester derivative.


Subject(s)
Amines/chemistry , Carbon/chemistry , Esters/chemistry , Molecular Structure , Stereoisomerism
2.
Chem Pharm Bull (Tokyo) ; 67(1): 71-74, 2019.
Article in English | MEDLINE | ID: mdl-30606952

ABSTRACT

A facile and convenient synthesis of trisubstituted (E)-α,ß-unsaturated esters was developed by improving our previously established method. The new method circumvented the separation of the intermediates, which have an activating group of the hydroxyl group in ß-hydroxy esters, furnishing α,ß-unsaturated esters in shorter steps than the previous method: an acetylation of ß-hydroxy group and subsequent E1cB reaction proceeded in tandem. In addition, the new method can not only employ a diastereomeric mixture of the substrate for the E1cB reaction, it has a wide substrate scope as well, which would enable the synthesis of various trisubstituted (E)-α,ß-unsaturated esters.


Subject(s)
Esters/chemical synthesis , Acetylation , Esters/chemistry , Molecular Structure , Stereoisomerism
3.
Chem Pharm Bull (Tokyo) ; 66(7): 714-720, 2018.
Article in English | MEDLINE | ID: mdl-29962454

ABSTRACT

We previously found that antioxidative activity of liposomes co-encapsulating astaxanthin (Asx) and tocotrienols (T3s) was higher than the calculated additive activity, which results from intermolecular interactions between both antioxidants (J. Clin. Biochem. Nutr., 59, 2016, Kamezaki et al.). Herein, we conducted experiments to optimize Asx/α-T3 ratio for high antioxidative activity, and tried to elucidate details of intermolecular interaction of Asx with α-T3. Higher activity than calculated additive value was clearly observed at an Asx/α-T3 ratio of 2 : 1, despite two α-T3 would potentially interact with two terminal rings of one Asx. The synthetic Asx used in this study was a mixture of three stereoisomers, 3R,3'R-form (Asx-R), 3S,3'S-form (Asx-S) and 3R,3'S-meso form (Asx-meso). The calculated binding energy of the Asx-S/α-T3 complex was higher than those of Asx-R/α-T3 and Asx-meso/α-T3, suggesting that Asx-S and α-T3 is the most preferable combination for the intermolecular interaction. The optimal Asx-S/α-T3 ratio for antioxidation was shown to be 1 : 2. These results suggest that the Asx stereochemistry affects the intermolecular interaction of Asx/α-T3. Moreover, the absorption spectrum changes of Asx-S upon co-encapsulation with α-T3 in liposomes indicate that the electronic state of Asx-S is affected by intermolecular interactions with α-T3. Further, intermolecular interactions with α-T3 affected the electronic charges on the C9, C10 and C15 atoms in the polyene moiety of Asx-S. In conclusion, the intermolecular interaction of Asx/T3 depends on the Asx stereochemistry, and caused a change in the electronic state of the Asx polyene moiety by the presence of double bond in the T3 triene moiety.


Subject(s)
Antioxidants/chemistry , Carotenoids/chemistry , Liposomes/chemistry , Tocotrienols/chemistry , Antioxidants/chemical synthesis , Liposomes/chemical synthesis , Molecular Structure , Stereoisomerism , Xanthophylls/chemical synthesis , Xanthophylls/chemistry
4.
J Clin Biochem Nutr ; 59(2): 100-106, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27698536

ABSTRACT

Astaxanthin and vitamin E are both effective antioxidants that are frequently used in cosmetics, as food additives, and in to prevent oxidative damage. A combination of astaxanthin and vitamin E would be expected to show an additive anntioxidative effect. In this study, liposomes co-encapsulating astaxanthin and the vitamin E derivatives α-tocopherol (α-T) or tocotrienols (T3) were prepared, and the antioxidative activity of these liposomes toward singlet oxygen and hydroxyl radical was evaluated in vitro. Liposomes co-encapsulating astaxanthin and α-T showed no additive anntioxidative effect, while the actual scavenging activity of liposomes co-encapsulating astaxanthin and T3 was higher than the calculated additive activity. To clarify why this synergistic effect occurs, the most stable structure of astaxanthin in the presence of α-T or α-T3 was calculated. Only α-T3 was predicted to form hydrogen bonding with astaxanthin, and the astaxanthin polyene chain would partially interact with the α-T3 triene chain, which could explain why there was a synergistic effect between astaxanthin and T3 but not α-T. In conclusion, co-encapsulation of astaxanthin and T3 induces synergistic scavenging activity by intermolecular interactions between the two antioxidants.

5.
Chemistry ; 19(22): 7056-63, 2013 May 27.
Article in English | MEDLINE | ID: mdl-23576314

ABSTRACT

The stereochemistry around the N-benzoylated indole moiety of indometacin was studied by restricting the rotation about the N-C7' and/or C7'-C1' bond. In the 2',6'-disubstituted ones, an atropisomeric property was found and the atropoisomers were separated and isolated as stable forms. Their biological abilities to inhibit cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) were examined. Only the aR-isomer showed specific inhibition of COX-1, and COX-2 was not inhibited by either atropisomer. Conformational analysis in NMR studies and X-ray crystallography, and CD spectra in combination with calculations were utilized to elucidate the bioactive conformations.


Subject(s)
Cyclooxygenase Inhibitors/chemistry , Indomethacin/chemistry , Crystallography, X-Ray , Cyclooxygenase Inhibitors/chemical synthesis , Cyclooxygenase Inhibitors/pharmacology , Drug Design , Indomethacin/analogs & derivatives , Indomethacin/chemical synthesis , Indomethacin/pharmacology , Magnetic Resonance Spectroscopy , Molecular Conformation , Stereoisomerism , Structure-Activity Relationship
6.
Steroids ; 77(12): 1198-204, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22842233

ABSTRACT

Circular dichroism (CD) spectra of the 2,2'-binaphthyl ester derived from Δ(5)-sterols showed not bisignate CD but diagnostic CD bands at around 210 and 240 nm. These bands might be attributable to an interaction between an olefinic chromophore and a binaphthyl one. Various types of unsaturated sterols were thus derivatized followed by complete hydrogenation, to give saturated sterols. As a result, CD spectra of the binaphthyl derivatives of the saturated sterols showed bisignate curves centered at 240 nm (3S(ß): positive chirality; 3R(α): negative one). This suggested a straightforward and practical method for discriminating the absolute stereogenic center at the C-3 positions of sterols based on an induced CD. This finding should contribute significantly to the analysis of metabolites of various types of sterols.


Subject(s)
Circular Dichroism/methods , Sterols/chemistry , Hydrogenation , Spectrophotometry, Ultraviolet
7.
J Org Chem ; 75(12): 4201-11, 2010 Jun 18.
Article in English | MEDLINE | ID: mdl-20481590

ABSTRACT

Multiple contiguous chiral centers were constructed in one pot using three types of multistep reactions initiated with the Michael addition of N-benzyl-2(R)-methoxy-(+)-10-bornylamide to alpha,beta-unsaturated esters, i.e., asymmetric Michael-aldol reaction, double Michael addition, and double Michael-aldol reaction. The chiral 2-methoxy-10-bornyl group as well as the benzyl group on the amino group of the products in the Michael-aldol reaction could be easily cleaved by treatment with NIS (4 equiv), and beta-amino esters with multiple contiguous chiral centers were obtained in good yield. As an application, the beta-amino-beta'-hydroxy ester obtained in the asymmetric Michael-aldol reaction was converted to the beta-lactam derivative in good yield.


Subject(s)
Amines/chemical synthesis , Esters/chemistry , Amines/chemistry , Molecular Structure , Stereoisomerism
8.
Nat Prod Commun ; 5(11): 1733-6, 2010 Nov.
Article in English | MEDLINE | ID: mdl-21213969

ABSTRACT

A straightforward strategy is reported for chiral discrimination in a specified carotenoid using a CD band, which is insensitive to conformational changes, computed by quantum chemical calculation.


Subject(s)
Carotenoids/chemistry , Circular Dichroism/methods , Xanthophylls/chemistry , Molecular Structure , Quantum Theory
9.
J Nat Med ; 62(3): 345-8, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18404300

ABSTRACT

In this study, we analyzed the CYP3A inhibitory components of star fruit Averrhoa carambola L., using liquid chromatography-mass spectrometry (LC-MS). The stereoisomer of procyanidin B1 and B2 and/or the trimer consisting of catechin and/or epicatechin were suggested to be potent inhibitory components.


Subject(s)
Cytochrome P-450 Enzyme Inhibitors , Magnoliopsida/chemistry , Plant Extracts/pharmacology , Biflavonoids/isolation & purification , Biflavonoids/pharmacology , Catechin/isolation & purification , Catechin/pharmacology , Chromatography, Liquid , Cytochrome P-450 CYP3A , Fruit , Humans , In Vitro Techniques , Mass Spectrometry , Microsomes, Liver/enzymology , Microsomes, Liver/metabolism , Plant Extracts/chemistry , Proanthocyanidins/isolation & purification , Proanthocyanidins/pharmacology , Stereoisomerism
10.
J Nat Med ; 62(3): 354-5, 2008 Jul.
Article in English | MEDLINE | ID: mdl-18404305

ABSTRACT

Six phenolic compounds were isolated from the flowers of Trachelospermum asiaticum var. intermedium (Apocynaceae). These structures were determined on the basis of spectral data.


Subject(s)
Apocynaceae/chemistry , Phenols/isolation & purification , Plant Extracts/chemistry , Flowers , Magnetic Resonance Spectroscopy
11.
Phytochem Anal ; 17(1): 20-4, 2006.
Article in English | MEDLINE | ID: mdl-16454472

ABSTRACT

(2S, 3S)-Taxifolin 3-O-arabinoside, a new dihydroflavonol glycoside, together with the known substances, (2R 3R)-taxifolin 3-O-arabinoside, astragalin, isoquercitrin, and cosmosiin, were isolated from the leaves of Trachelospermum jasminoides var. pubescens. Structural elucidation was carried out by spectroscopic methods, and the absolute configurations of C-2 and C-3 in taxifolin 3-O-arabinosides were determined on the basis of circular dichroism. Unlike the dihydroflavonol glycosides, (2R 3R)-taxifolin 3-O-glucoside and (2R, 3R-taxifolin 3-O-arabinoside, the novel (2S, 3S)-taxifolin 3-O-arabinoside is not effective as a zoospore attractant of the plant pathogenic fungus Aphanomyces cochlioides.


Subject(s)
Apocynaceae/chemistry , Glycosides/chemistry , Chromatography, High Pressure Liquid , Circular Dichroism , Molecular Structure , Plant Leaves/chemistry , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, Ultraviolet
12.
J Nat Med ; 60(3): 240-242, 2006 Jul.
Article in English | MEDLINE | ID: mdl-29435884

ABSTRACT

The present study was conducted to identify cytochrome P450 3A (CYP3A) inhibitory components of Hyuganatsu, Citrus tamurana Hort., by investigating the effects on midazolam 1'-hydroxylase activity of human liver microsomes. As a consequence, limonin and nomilin were identified as CYP3A inhibitors from the endocarp of Hyuganatsu.

13.
J Nat Prod ; 67(9): 1568-70, 2004 Sep.
Article in English | MEDLINE | ID: mdl-15387661

ABSTRACT

A modified procedure for determining absolute configurations using an induced CD method and molecular mechanics calculations is disclosed. The practical usefulness of the present technique was demonstrated by its application to a few natural products.


Subject(s)
Biological Products/chemistry , Circular Dichroism/methods , Models, Molecular , Computational Biology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , Rubiaceae/chemistry
14.
Anal Sci ; 19(6): 973-4, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12834250

ABSTRACT

The structure of the Diels-Alder cycloadduct formed from 2-(1,2,3-1H-benzotriazol-1-yl)-2-(p-tolyl)-2H-isoindole and dimethyl acetylenedicarboxylate was proved as 11-aza-1-(1,2,3-1H-benzotriazol-1-yl)-11-(4-methylphenyl)-tricyclo-[5.2.1.0(2.7)]undeca-2,4,6.9-tetraene-9,10-dioic acid dimethyl ester. The benzotriazole moiety was located as its 1-yl form, analogous to previous reports. The benzotriazole and the benzene (of tricyclo framework) planes were twisted with an angle of 115.83 degrees. Intramolecular close contacts between benzotriazole and ester are characteristic [N(3)...C(26), 2.754(3)A; N(3)...H(22), 3.26(4)A]. The shortest contact of N(3)...H(22) accounting for the rotation of the methyl group is estimated to be 3.10 A, which might be reasonable as C-H...N-type hydrogen bonding.

15.
Anal Sci ; 19(5): 807-8, 2003 May.
Article in English | MEDLINE | ID: mdl-12769392

ABSTRACT

In the crystal structure of TBM-trihydrate three waters of crystallization were found to locate dissymmetrically. Thus, one of them forms a chelated ring with the neighboring C=O and N-H of TBM. Two other ones bind each other through hydrogen bonding and two sets of which form a cyclic dimer by hydrogen bonding (namely, water-tetramer). A C=O group binds by hydrogen bonding to each of the tetrameric water. The spatial volume occupied by water-tetramer appears to be sufficient for complexation with organic molecules.

18.
Bioorg Med Chem ; 10(4): 969-73, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11836106

ABSTRACT

We investigated the inhibitory activity of the furanocoumarin derivatives from grapefruit juice to the drug metabolizing enzyme, cytochrome P450 (CYP) 3A4. Although two known furanocoumarin dimers GF-I-1 (1) and GF-I-4 (2) showed potent CYP3A4 inhibition with IC50 value of 0.07 microM, a semi-synthetic dihydroxybergamottin caproate (11), which was more stable and more simple than the dimers, exhibited comparable activity against CYP3A4.


Subject(s)
Caproates/pharmacology , Cytochrome P-450 Enzyme Inhibitors , Enzyme Inhibitors/chemical synthesis , Furocoumarins/pharmacology , Mixed Function Oxygenases/antagonists & inhibitors , Caproates/chemistry , Citrus/chemistry , Cytochrome P-450 CYP3A , Drug Stability , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Furocoumarins/chemistry , Inhibitory Concentration 50 , Structure-Activity Relationship
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