ABSTRACT
The cryptolactones A1, A2, B1, and B2 isolated from a Cryptomyzus sp. aphid were synthesized via the Mukaiyama aldol reaction and olefin metathesis. Their antipodes and derivatives were also synthesized by the same strategy to investigate structure-activity relationships. These compounds exhibited cytotoxic activity against human promyelocytic leukemia HL-60 cells with IC50 values of 2.1-42 µM.
Subject(s)
Antineoplastic Agents/pharmacology , Aphids/chemistry , Lactones/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Cell Proliferation/drug effects , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , HL-60 Cells , Humans , Lactones/chemical synthesis , Lactones/chemistry , Molecular Structure , Stereoisomerism , Structure-Activity RelationshipABSTRACT
Four red polyketide pigments, uroleuconaphins A1 (1) and B1 (2) and their glucosides 3 and 4, were isolated from the red goldenrod aphid Uroleucon nigrotuberculatum. Although these red pigments exist only as glucosides 3 and 4 in the intact insect body, 3 and 4 convert instantly to aglycones 1 and 2 at death. Pigments 1 and 2 inhibited the growth of Lecanicillium sp. (Ascomycota: Cordycipitaceae) and 1, 2, and 3 were active against Conidiobolus obscurus (Entomophthoromycota; Entomophthorales); these fungal species are pathogenic. We therefore regard aphid pigments 1-4 as chemopreventive agents that aid in the resistance of infection by entomopathogenic fungi at the level of the individual aphid and/or at the species level.
Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Aphids/chemistry , Aphids/microbiology , Fungi/drug effects , Mycoses/microbiology , Mycoses/prevention & control , Polyketides/chemistry , Polyketides/pharmacology , Animals , Ascomycota/drug effects , Fungi/growth & development , Glucosides/chemistry , Hypocreales , Sugars/chemistryABSTRACT
The cryptolactones A1, A2, B1, and B2, which are α,ß-unsaturated δ-lactones, were isolated from a Cryptomyzus sp. aphid. The structures were established by 1-D and 2-D NMR spectra and CI-HRMS. Their absolute configurations were determined with the Kusumi-Mosher method, combined with asymmetric total syntheses. The syntheses were accomplished with the Mukaiyama aldol reaction and olefin metathesis, which utilized the second-generation Grubbs catalyst for the key steps. These compounds exhibited cytotoxic activity against human promyelocytic leukemia HL-60 cells with IC50 values of 0.97-5.3 µM.
Subject(s)
Alkenes/chemistry , Antineoplastic Agents , Lactones , Aldehydes/chemistry , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Aphids , Catalysis , HL-60 Cells , Humans , Japan , Lactones/chemical synthesis , Lactones/chemistry , Lactones/isolation & purification , Lactones/pharmacology , Molecular Structure , Nuclear Magnetic Resonance, Biomolecular , StereoisomerismABSTRACT
A green pigment, viridaphin A1 glucoside (1), was isolated from the green aphid Megoura crassicauda. One- and two-dimensional NMR spectrometric analyses of 1 and its aglycone established the structure as an octacyclic compound. Viridaphin A1 glucoside exhibited cytotoxicity against HL-60 human tumor cells with an IC50 of 23 µM and antibacterial activity against Bacillus subtilis NBRC 3134 with a minimum inhibitory concentration of 10.0 µg/mL. These results suggested that aphid pigments may protect aphids from invasive species, including viruses and bacteria.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/isolation & purification , Antineoplastic Agents/pharmacology , Aphids/chemistry , Glucosides/isolation & purification , Glucosides/pharmacology , Pigments, Biological/isolation & purification , Pigments, Biological/pharmacology , Animals , Anti-Bacterial Agents/chemistry , Antineoplastic Agents/chemistry , Aphids/physiology , Drug Screening Assays, Antitumor , Glucosides/chemistry , HL-60 Cells , Humans , Inhibitory Concentration 50 , Japan , Microbial Sensitivity Tests , Nuclear Magnetic Resonance, Biomolecular , Pigments, Biological/chemistryABSTRACT
Utilizing host-guest inclusion complexation in the solid state, alpha-monosubstituted ketones were deracemized using optically active host compounds such as (-)-trans-2,3-bis(hydroxydiphenylmethyl)-1,4-dioxaspiro[5.4]decene (1a) under alkali conditions. This new method afforded optically active alpha-monosubstituted ketones in excellent yields with high enantiomeric excesses. For example, (+/-)-2-benzylcyclohexanone (2a) and (+/-)-3-benzylhexan-2-one (3c) were converted to the R-isomer (74% ee) and the S-isomer (96% ee), respectively, in quantitative yields. An x-ray crystallographic study elucidated the structure of the inclusion complex of 1a and (R)-2a. The study showed that the host molecules 1a ingeniously includes the guest molecule (R)-2a via hydrogen bonding and van der Waals interactions. As an application of deracemization, coenzyme (R)-alpha-lipoic acid and (R)-(-)-epilachnene, the antipode of an defensive droplets from the Mexican bean beetle, Epilachna varivestis, were synthesized in short steps with>99% ee and 87% ee, respectively.
Subject(s)
Chemistry, Organic/methods , Ketones/chemical synthesis , Thermodynamics , Alkaloids/chemical synthesis , Animals , Bridged-Ring Compounds/chemical synthesis , Coleoptera , Crystallography, X-Ray , Hydrogen Bonding , Ketones/chemistry , Stereoisomerism , Thioctic Acid/chemical synthesisABSTRACT
(+)-Antimycin A9 (AA9) isolated from a cultured broth of Streptomyces sp. K01-0031 was synthesized via an asymmetric aldol reaction using Oppolzer's sultam as a chiral auxiliary.
Subject(s)
Antimycin A/analogs & derivatives , Antimycin A/chemical synthesis , Antimycin A/chemistry , Molecular StructureABSTRACT
(Cyanomethylene)tributylphosphorane (CMBP), which promoted the alkylation of various nucleophiles (HA) with alcohols (ROH) to give RA (Mitsunobu-type reaction), was prepared in two steps starting from chloroacetonitrile.
Subject(s)
Indicators and Reagents/chemical synthesis , Acetonitriles , Alcohols , Alkylation , Magnetic Resonance Spectroscopy , TolueneABSTRACT
(Cyanomethylene)trimethylphosphorane (CMMP) mediates Mitsunobu-type reactions, which are a versatile method for the alkylation of various nucleophiles (HA) with alcohols (ROH) to give RA. CMMP is quite effective for the reaction of carbon nucleophiles whose pK(a) value are higher than 13. CMMP, which is very sensitive to air and moisture, was synthesized in two steps starting from chloroacetonitrile.
