An efficient synthesis of -(alkylidene)-5, 5-dimethyl- -lactones

Cheminform, 2010

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Tetrahedron Letters, 2000

Cross-coupling reactions of (E)-and (Z)-tosylates of α-hydroxymethylene-γ-butyrolactone with aryl, heteroaryl, alkyl, and alkynylzinc chlorides under Pd(PPh 3) 4 catalysis were found to be a suitable synthetic method for stereoselective preparation of α-alkylideneand substituted alkylidene-γ-lactones. The reactions, conducted under mild conditions, proceed with high stereoselectivity and moderate yields.

Journal of Organic Chemistry, 2022

Bioorganic & medicinal …, 2010

Marine agonist a b s t r a c t A novel class of natural PPAR agonists, 2,4-dimethyl-4-hydroxy-16-phenylhexadecanoic acid 1,4-lactone (1), were discovered in marine natural product libraries. The synthesis of 1 was accomplished starting from vinylmethyl ketone. Ring formation of the a,c dialkyl c-lactone was achieved via the stereo-controlled reaction of a ketyl radical anion with a chiral methacrylate. In the PPAR agonistic assay, the most potent of the four stereoisomers had EC 50 values of 12 lM for mPPARa, 9 lM for mPPARd and >100 lM for mPPARc.

Tetrahedron, 1987

The reaction of several carbohydrate-derived alkoxgaldehydes with methoxycarbonylmethylen~riphenglphosphorane' affords ~,B -unsaturated esters • with Z-stereos~lectivity. The stereos~ectivity depends on the substrate structure and the nature of the solvent used. a 1 As a part of our synthetic studies on naturally occurring ~B-unsaturated-6-1actones , the stereoselective synthesis of Z-a,B-unsaturated esters was needed. The a,B-unsaturated esters are useful synthetic intermediates as Michael acceptors 2 and as precursors of allylic alcohols 3 and there is a necessity of obtaining them stereoselectively. Both the Wittig 4 and the Wittig-Horner 5 reaction using alkoxycarbonylphosphoranes or phosphonates generally yield the 4,B-unsaturated esters with E-configuration and there are only a few methods which afford the Z-isomer. The bis(trifluoroethyl)phosphone ester 1 have been used to obtain diand tri-suhstituted a ,B -unsaturated esters with good stereoselectivity 6 and ethyl a-(dimethylphosphono)

Tetrahedron Letters, 1985

Optically pure (+)-R-(4methylphenyl)sulphoxides were lithiated and alkylated with lithium a-bromomethyl acrylate with medium to high diastereoselection; condensation products gave in two steps optically pure a-methylene-y-lactones.

European Journal of Medicinal Chemistry, 2010

We present a simple and general strategy for the synthesis of b,d-disubstituted-a-methylene-d-lactones starting from easily available tert-butyl 2-(diethoxyphosphoryl)alk-2-enoates. The elaborated synthetic protocol includes pyrrolidine-catalyzed Michael addition of acetone, diastereoselective reduction of the carbonyl group, lactonization and finally the Horner-Wadsworth-Emmons reaction with formaldehyde.

International Journal of Pharmaceutical Research, 2018

The α-methylene-γ-butyrolactone skeleton is part of many natural products with remarkable biological properties. C75, a fatty acid synthase (FAS) inhibitor, is a synthetic α-methylene-γ-butyrolactone which is cytotoxic for different cell lines in vitro and in vivo against human cancer xenografts. We synthesized a panel of C75 derivatives through modifications of the α-methylene moiety at the C-β/C- carbons of the γ-butyrolactone skeleton and tested their effects on different cancer models. The in vitro effects of the compounds on pancreatic, colon and breast cancer cell viability (PANC-1, HTC-116, Lovo, MCF-7, MDA-231-MB) were evaluated. Two compounds showed significant cytotoxicity. The structures of all synthesized compounds obtained were identified on the basis of their spectral data (IR, MS, NMR).

Bioorganic & Medicinal Chemistry, 2008

A series of 5-aryl-3-alkylidenedihydrofuran-2(3H)-ones 6a-g 00 and 11a,b as well as 5-aryl-3-methylidenepyrrolidin-2-ones 10a-c and 12 were synthesized starting from 4-aryl-2-diethoxyphosphoryl-4-oxobutanoates 3a-g. Reaction sequence includes reduction or reductive amination of the carbonyl group, lactonization or lactamization step and finally the Horner-Wadsworth-Emmons olefination of aldehydes using thus obtained 5-aryl-3-diethoxyphosphoryl-3,4-dihydrofuran-2(5H)-ones 5a-g 00 or 5-aryl-3-diethoxyphosphorylpyrrolidin-2-ones 9a-c. Furanones 6 and 11, as well as pyrrolidinones 10 and 12, were evaluated in vitro against mouse leukemia cell line L-1210 and two human leukemia cell lines HL-60 and NALM-6. Several of the obtained furanones proved to be very potent against all three cell lines with IC 50 values lower than 6 lM. Structure-activity relationships of these compounds, as well as 5-alkyl or 5-arylmethyl-3-methylidenedihydrofuran-2(3H)-ones 13a-e, previously obtained in our laboratory, are discussed.

Heterocyclic Communications, 2002

fiiran -l,2-dione(l), isatin (8a), N-methylisatin (8b) and/or N-acetyl isatin (8c) can be converted by reaction with N-phenyliminovinylidene-(2a), 2-oxovinylidene-(2b) and/or 2-thioxovinylidentriphenylphosphorane (2c) into the corresponding phosphoranylidene-cyclobutylidene derivatives (5a-c) and (9a-i) respectively. The structure of the new cyclobutylidenes was confirmed on the bases of elemental analysis and spectral studies.